Trial Outcomes & Findings for Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer (NCT NCT00217737)

NCT ID: NCT00217737

Last Updated: 2025-12-03

Results Overview

Disease-free survival (DFS) is defined as the time from randomization to the earlier of disease recurrence, new invasive primary cancer, or death from any cause. The Kaplan-Meier estimates were used to characterize the 5-year DFS rates.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE3
• Target enrollment: 2431 participants
• Primary outcome timeframe: Assessed every 3 months for patients within 2 years of step 2 randomization, every 6 months during 3-5 years from step 2 randomization, and then every 12 months until 10 years from step 2 randomization
• Results posted on: 2025-12-03

Participant Flow

The study was activated on August 4th, 2005 and was closed to accrual on February 11th, 2011. A total of 2,431 patients were enrolled.

Participant milestones

Measure	Arm A (5-FU, Leucovorin, Oxaliplatin) Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm B (5-FU, Leucovorin, Oxaliplatin, Bevacizumab) Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in Arm A and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone for 12 additional courses in the absence of disease progression or unacceptable toxicity.	Arm C (Observation) Patients undergo observation.	No Randomization/Registration at Step 2 Patients whose risk assessment information was unavailable or who did not registered to Step 2 are included in this group.
Step 1 Registration (Risk Assessment) STARTED	460	458	1013	500
Step 1 Registration (Risk Assessment) COMPLETED	460	458	1013	0
Step 1 Registration (Risk Assessment) NOT COMPLETED	0	0	0	500
Step 2 Randomization/Registration STARTED	460	458	1013	0
Step 2 Randomization/Registration Eligible Patients	424	435	998	0
Step 2 Randomization/Registration Received Treatment	429	410	0	0
Step 2 Randomization/Registration Received Treatment and Toxicity Data Available	428	410	0	0
Step 2 Randomization/Registration Included in the Analysis of Impact of Tumor Biological Characteristics on Survival	326	324	718	0
Step 2 Randomization/Registration COMPLETED	304	143	1013	0
Step 2 Randomization/Registration NOT COMPLETED	156	315	0	0

Reasons for withdrawal

Measure	Arm A (5-FU, Leucovorin, Oxaliplatin) Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm B (5-FU, Leucovorin, Oxaliplatin, Bevacizumab) Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in Arm A and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone for 12 additional courses in the absence of disease progression or unacceptable toxicity.	Arm C (Observation) Patients undergo observation.	No Randomization/Registration at Step 2 Patients whose risk assessment information was unavailable or who did not registered to Step 2 are included in this group.
Step 1 Registration (Risk Assessment) Withdrawal by Subject	0	0	0	252
Step 1 Registration (Risk Assessment) No tumor block assessments	0	0	0	83
Step 1 Registration (Risk Assessment) Ineligible	0	0	0	68
Step 1 Registration (Risk Assessment) Uninformative tumor block	0	0	0	18
Step 1 Registration (Risk Assessment) Physician Decision	0	0	0	16
Step 1 Registration (Risk Assessment) Study suspension/closure before treatment	0	0	0	16
Step 1 Registration (Risk Assessment) Staff/site error	0	0	0	9
Step 1 Registration (Risk Assessment) Unable to follow treatment schedule	0	0	0	9
Step 1 Registration (Risk Assessment) Adverse Event	0	0	0	6
Step 1 Registration (Risk Assessment) Insurance issues	0	0	0	4
Step 1 Registration (Risk Assessment) Non-compliance	0	0	0	2
Step 1 Registration (Risk Assessment) Death	0	0	0	1
Step 1 Registration (Risk Assessment) Disease progression	0	0	0	1
Step 1 Registration (Risk Assessment) Inadequate supply of Leucovorin	0	0	0	1
Step 1 Registration (Risk Assessment) Lost to Follow-up	0	0	0	1
Step 1 Registration (Risk Assessment) Other	0	0	0	12
Step 1 Registration (Risk Assessment) Registration error	0	0	0	1
Step 2 Randomization/Registration Adverse Event	59	98	0	0
Step 2 Randomization/Registration Withdrawal by Subject	53	105	0	0
Step 2 Randomization/Registration Study suspension	0	45	0	0
Step 2 Randomization/Registration Complicating disease	5	5	0	0
Step 2 Randomization/Registration Death	2	3	0	0
Step 2 Randomization/Registration Non-compliant	2	4	0	0
Step 2 Randomization/Registration Physician Decision	2	2	0	0
Step 2 Randomization/Registration Alternative therapy	0	1	0	0
Step 2 Randomization/Registration Extraordinary Medical Circumstances	0	1	0	0
Step 2 Randomization/Registration Found to be Ineligible After Treatment	0	1	0	0
Step 2 Randomization/Registration Incorrect Cancer Stage	1	0	0	0
Step 2 Randomization/Registration Never started protocol therapy	31	48	0	0
Step 2 Randomization/Registration Other	1	2	0	0

Baseline Characteristics

One patient with unknown sex was excluded from the analysis of distribution of sex.

Baseline characteristics by cohort

Measure	Arm A (5-FU, Leucovorin, Oxaliplatin) n=460 Participants Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm B (5-FU, Leucovorin, Oxaliplatin, Bevacizumab) n=458 Participants Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in Arm A and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone for 12 additional courses in the absence of disease progression or unacceptable toxicity.	Arm C (Observation) n=1013 Participants Patients undergo observation.	Total n=1931 Participants Total of all reporting groups
Age, Continuous	59 years n=460 Participants	59 years n=458 Participants	60 years n=1013 Participants	60 years n=1931 Participants
Sex: Female, Male Female	235 Participants n=459 Participants • One patient with unknown sex was excluded from the analysis of distribution of sex.	232 Participants n=458 Participants • One patient with unknown sex was excluded from the analysis of distribution of sex.	496 Participants n=1013 Participants • One patient with unknown sex was excluded from the analysis of distribution of sex.	963 Participants n=1930 Participants • One patient with unknown sex was excluded from the analysis of distribution of sex.
Sex: Female, Male Male	224 Participants n=459 Participants • One patient with unknown sex was excluded from the analysis of distribution of sex.	226 Participants n=458 Participants • One patient with unknown sex was excluded from the analysis of distribution of sex.	517 Participants n=1013 Participants • One patient with unknown sex was excluded from the analysis of distribution of sex.	967 Participants n=1930 Participants • One patient with unknown sex was excluded from the analysis of distribution of sex.
Ethnicity (NIH/OMB) Hispanic or Latino	29 Participants n=460 Participants	32 Participants n=458 Participants	88 Participants n=1013 Participants	149 Participants n=1931 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	401 Participants n=460 Participants	390 Participants n=458 Participants	868 Participants n=1013 Participants	1659 Participants n=1931 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	30 Participants n=460 Participants	36 Participants n=458 Participants	57 Participants n=1013 Participants	123 Participants n=1931 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=460 Participants	2 Participants n=458 Participants	0 Participants n=1013 Participants	3 Participants n=1931 Participants
Race (NIH/OMB) Asian	17 Participants n=460 Participants	14 Participants n=458 Participants	32 Participants n=1013 Participants	63 Participants n=1931 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=460 Participants	0 Participants n=458 Participants	0 Participants n=1013 Participants	0 Participants n=1931 Participants
Race (NIH/OMB) Black or African American	49 Participants n=460 Participants	55 Participants n=458 Participants	85 Participants n=1013 Participants	189 Participants n=1931 Participants
Race (NIH/OMB) White	385 Participants n=460 Participants	372 Participants n=458 Participants	882 Participants n=1013 Participants	1639 Participants n=1931 Participants
Race (NIH/OMB) More than one race	2 Participants n=460 Participants	0 Participants n=458 Participants	0 Participants n=1013 Participants	2 Participants n=1931 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=460 Participants	15 Participants n=458 Participants	14 Participants n=1013 Participants	35 Participants n=1931 Participants

PRIMARY outcome

Timeframe: Assessed every 3 months for patients within 2 years of step 2 randomization, every 6 months during 3-5 years from step 2 randomization, and then every 12 months until 10 years from step 2 randomization

Population: Eligible patients who were registered or randomized at Step 2 were included in this analysis.

Disease-free survival (DFS) is defined as the time from randomization to the earlier of disease recurrence, new invasive primary cancer, or death from any cause. The Kaplan-Meier estimates were used to characterize the 5-year DFS rates.

Outcome measures

Measure	Arm A (5-FU, Leucovorin, Oxaliplatin) n=424 Participants Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm B (5-FU, Leucovorin, Oxaliplatin, Bevacizumab) n=435 Participants Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in Arm A and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone for 12 additional courses in the absence of disease progression or unacceptable toxicity.	Arm C (Observation) n=998 Participants Patients undergo observation.
Disease-free Survival Rate at 5 Years	0.805 Proportion of participants Interval 0.766 to 0.846	0.833 Proportion of participants Interval 0.796 to 0.871	0.816 Proportion of participants Interval 0.791 to 0.842

SECONDARY outcome

Timeframe: Assessed every 3 months for patients within 2 years of step 2 randomization, every 6 months during 3-5 years from step 2 randomization, and then every 12 months until 10 years from step 2 randomization

Population: Eligible patients who were registered or randomized at Step 2 were included in this analysis.

Overall survival (OS) is defined as the time from randomization to death from any cause. OS is censored at the date of last contact for patients still alive. The Kaplan-Meier estimates were used to characterize the 5-year OS rates.

Outcome measures

Measure	Arm A (5-FU, Leucovorin, Oxaliplatin) n=424 Participants Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm B (5-FU, Leucovorin, Oxaliplatin, Bevacizumab) n=435 Participants Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in Arm A and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone for 12 additional courses in the absence of disease progression or unacceptable toxicity.	Arm C (Observation) n=998 Participants Patients undergo observation.
Overall Survival Rate at 5 Years	0.918 Proportion of participants Interval 0.891 to 0.946	0.921 Proportion of participants Interval 0.895 to 0.948	0.926 Proportion of participants Interval 0.909 to 0.943

SECONDARY outcome

Timeframe: Assessed at baseline, every 3 months for patients within 2 years of step 2 randomization, every 6 months during 3-5 years from step 2 randomization, and then every 12 months until 10 years from step 2 randomization

Population: Eligible patients who had advanced to step 2 (Arms A, B and C) and had complete data on patient/tumor characteristics are included.

Overall survival (OS) is defined as the time from randomization to death from any cause. OS is censored at the date of last contact for patients still alive. The following patient/tumor characteristics were associated with overall survival:

• ECOG Performance Status (0, 1, or 2)
• Age
• Sex (male, female)
• Primary tumor site (right-side colon, transverse colon, left-side colon, or other)
• Number of regional lymph nodes

Hazard ratios with adjustment for other covariates are reported with OS as the outcome variable.

Outcome measures

Measure	Arm A (5-FU, Leucovorin, Oxaliplatin) n=1368 Participants Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm B (5-FU, Leucovorin, Oxaliplatin, Bevacizumab) Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in Arm A and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone for 12 additional courses in the absence of disease progression or unacceptable toxicity.	Arm C (Observation) Patients undergo observation.
The Impact of Tumor Biological Characteristics on Overall Survival Hazard ratio: ECOG performance status of 1 (vs. 0)	1.67 hazard ratio Interval 1.24 to 2.25	—	—
The Impact of Tumor Biological Characteristics on Overall Survival Hazard ratio: ECOG performance status of 2 (vs. 0)	3.39 hazard ratio Interval 1.36 to 8.44	—	—
The Impact of Tumor Biological Characteristics on Overall Survival Hazard ratio: Age	1.05 hazard ratio Interval 1.04 to 1.07	—	—
The Impact of Tumor Biological Characteristics on Overall Survival Hazard ratio: Sex of male (vs. female)	1.71 hazard ratio Interval 1.27 to 2.28	—	—
The Impact of Tumor Biological Characteristics on Overall Survival Hazard ratio: Primary site of transverse colon (vs. Right-side colon)	0.81 hazard ratio Interval 0.44 to 1.52	—	—
The Impact of Tumor Biological Characteristics on Overall Survival Hazard ratio: Primary site of left-side colon (vs. Right-side colon)	1.13 hazard ratio Interval 0.82 to 1.55	—	—
The Impact of Tumor Biological Characteristics on Overall Survival Hazard ratio: Primary site of other (vs. Right-side colon)	2.68 hazard ratio Interval 1.39 to 5.17	—	—
The Impact of Tumor Biological Characteristics on Overall Survival Hazard ratio: Number of lymph nodes	0.98 hazard ratio Interval 0.96 to 0.99	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at baseline, every 2 weeks while on treatment, up to 10 years

The association between onset of neurotoxicity and oxaliplatin exposure will be assessed. The difference in neurotoxicity rates between patients with and without a given polymorphism will be evaluated.

Outcome measures

Outcome data not reported

Adverse Events

Arm A (5-FU, Leucovorin, Oxaliplatin)

Serious events: 308 serious events

Other events: 399 other events

Deaths: 73 deaths

Arm B (5-FU, Leucovorin, Oxaliplatin, Bevacizumab)

Serious events: 292 serious events

Other events: 388 other events

Deaths: 69 deaths

Arm C (Observation)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 145 deaths

No Randomization/Registration at Step 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 61 deaths

Serious adverse events

Measure	Arm A (5-FU, Leucovorin, Oxaliplatin) n=428 participants at risk Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm B (5-FU, Leucovorin, Oxaliplatin, Bevacizumab) n=410 participants at risk Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in Arm A and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone for 12 additional courses in the absence of disease progression or unacceptable toxicity.	Arm C (Observation) Patients undergo observation	No Randomization/Registration at Step 2 Patients whose risk assessment information was unavailable or who did not registered to Step 2 are included in this group.
Immune system disorders Allergic reaction	2.8% 12/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	1.7% 7/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Ear and labyrinth disorders Hearing w/o audiogr not in monitor prg	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Ear and labyrinth disorders Otitis, middle ear (non-infectious)	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Blood and lymphatic system disorders Anemia	0.70% 3/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Leukocytes decreased	9.8% 42/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	7.1% 29/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Lymphopenia	0.70% 3/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.73% 3/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Neutrophils decreased	41.6% 178/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	33.7% 138/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Platelets decreased	4.2% 18/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.73% 3/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Cardiac disorders Arrhythmia-other	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Cardiac disorders Cardiac-ischemia	0.70% 3/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Cardiac troponin I (cTnI) increased	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Vascular disorders Hypertension	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	8.8% 36/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Vascular disorders Hypotension	0.93% 4/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Cardiac disorders Left ventricular systolic dysfunction	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Cardiac disorders Cardiomyopathy, restrictive	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Cardiac disorders Valvular heart disease	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
General disorders Fatigue	7.7% 33/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	10.0% 41/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
General disorders Fever w/o neutropenia	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Psychiatric disorders Insomnia	0.70% 3/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
General disorders Rigors/chills	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Weight gain	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations INR increased	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.73% 3/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Coagulation-other	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
General disorders Injection site reaction	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Rash/desquamation	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	1.2% 5/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Hand-foot reaction	1.6% 7/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	3.9% 16/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Injury, poisoning and procedural complications Wound - non-infectious	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.73% 3/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Skin-other	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
General disorders Death - multiorgan failure	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Pancreatic glucose intolerance	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Anorexia	0.93% 4/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	2.7% 11/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Colitis	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Constipation	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Dehydration	3.3% 14/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	4.4% 18/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Diarrhea w/o prior colostomy	11.0% 47/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	13.4% 55/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Distention/bloating, abdominal	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Dysphagia	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Esophagitis	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Fistula, Rectum	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Gastritis	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Dyspepsia	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Hemorrhoids	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Ileus	0.93% 4/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.73% 3/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Injury, poisoning and procedural complications Leak, incl. anastomotic, large bowel	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	2.1% 9/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	1.2% 5/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Muco/stomatitis by exam, pharynx	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Muco/stomatitis (symptom) anus	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Muco/stomatitis (symptom) oral cavity	1.4% 6/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	1.7% 7/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Muco/stomatitis (symptom) pharynx	1.4% 6/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Nausea	4.0% 17/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	5.4% 22/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Hepatobiliary disorders Necrosis, gallbladder	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Obstruction, small bowel NOS	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Perforation, appendix	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Perforation, ileum	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Perforation, small bowel NOS	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Stenosis (incl anastomotic) colon	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Typhlitis	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Vomiting	2.6% 11/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	2.7% 11/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders GI-other	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders CNS, hemorrhage	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Colon, hemorrhage	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Lower GI, hemorrhage NOS	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Upper GI, hemorrhage NOS	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Renal and urinary disorders Urinary hemorrhage NOS	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Nose, hemorrhage	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Injury, poisoning and procedural complications Surgical hemorrhage	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Hepatobiliary disorders Cholecystitis	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Hepatobiliary disorders Liver dysfunction/failure	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Colitis, infectious (e.g. C.diff)	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Blood and lymphatic system disorders Febrile neutropenia	1.9% 8/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection w/ gr3-4 neut, catheter relate	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection w/ gr3-4 neut, ileum	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection w/ gr3-4 neut, lung	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection Gr0-2 neut, abdomen	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection Gr0-2 neut, appendix	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection Gr0-2 neut, bronchus	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection Gr0-2 neut, catheter	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.73% 3/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection Gr0-2 neut, colon	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection Gr0-2 neut, gallbladder	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection Gr0-2 neut, lung	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection Gr0-2 neut, oral cavity	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection Gr0-2 neut, peritoneal	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection Gr0-2 neut, skin	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Infection w/ unk ANC urinary tract NOS	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Infections and infestations Opportunistic infection lymphopenia>=gr1	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypoalbuminemia	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Alanine aminotransferase increased	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.98% 4/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Serum amylase increased	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Aspartate aminotransferase increased	0.70% 3/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.98% 4/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Blood bilirubin increased	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypocalcemia	0.70% 3/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Hypercholesterolemia	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Creatinine increased	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.73% 3/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations GGT increased	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyperglycemia	1.9% 8/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.98% 4/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Lipase increased	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyperkalemia	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypokalemia	3.3% 14/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	3.2% 13/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Renal and urinary disorders Proteinuria	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	1.2% 5/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyponatremia	0.70% 3/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	1.7% 7/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyperuricemia	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Metabolic/Laboratory-other	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Nonneuropathic lower extr muscle weak	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Nonneuropathic upper extr muscle weak	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Nonneuropathic generalized weakness	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Soft tissue necrosis, head	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders CNS cerebrovascular ischemia	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Dizziness	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.98% 4/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Laryngeal nerve dysfunction	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Mental status	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Psychiatric disorders Depression	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Neuropathy CN V jaw / face-sensory	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Neuropathy-motor	0.70% 3/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Neuropathy-sensory	18.7% 80/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	19.0% 78/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Seizure	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Depressed level of consciousness	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Syncope	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	1.5% 6/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Tremor	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Neurologic-other	1.4% 6/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	1.2% 5/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Eye disorders Vision-flashing lights/floaters	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Eye disorders Ocular-other	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Abdomen, pain	1.6% 7/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	2.9% 12/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Back, pain	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Bone, pain	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Buttock, pain	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
General disorders Pain NOS	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Cardiac disorders Cardiac/heart, pain	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
General disorders Chest/thoracic pain NOS	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Extremity-limb, pain	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Hepatobiliary disorders Gallbladder, pain	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Head/headache	1.2% 5/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.98% 4/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Joint, pain	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Muscle, pain	1.4% 6/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	1.2% 5/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Neck, pain	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Oral cavity, pain	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Pleura, pain	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
General disorders Pain-other	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders (ARDS)	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.70% 3/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	1.5% 6/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Hiccoughs	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.24% 1/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Renal and urinary disorders Renal failure	0.23% 1/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	0.70% 3/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.49% 2/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.70% 3/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Immune system disorders Cytokine release syndrome	0.47% 2/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	0.00% 0/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Injury, poisoning and procedural complications Vascular access,Thrombosis/embolism	1.6% 7/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	2.7% 11/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Vascular disorders Thrombosis/thrombus/embolism	2.1% 9/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	4.6% 19/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.

Other adverse events

Measure	Arm A (5-FU, Leucovorin, Oxaliplatin) n=428 participants at risk Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.	Arm B (5-FU, Leucovorin, Oxaliplatin, Bevacizumab) n=410 participants at risk Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in Arm A and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab alone for 12 additional courses in the absence of disease progression or unacceptable toxicity.	Arm C (Observation) Patients undergo observation	No Randomization/Registration at Step 2 Patients whose risk assessment information was unavailable or who did not registered to Step 2 are included in this group.
Blood and lymphatic system disorders Anemia	54.9% 235/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	50.0% 205/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Leukocytes decreased	51.9% 222/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	42.4% 174/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Neutrophils decreased	43.0% 184/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	38.0% 156/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Platelets decreased	53.0% 227/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	37.1% 152/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Vascular disorders Hypertension	2.8% 12/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	27.1% 111/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
General disorders Fatigue	68.7% 294/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	67.8% 278/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Psychiatric disorders Insomnia	8.4% 36/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	7.3% 30/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Weight loss	4.4% 19/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	8.0% 33/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Alopecia	23.8% 102/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	20.7% 85/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Hyperpigmentation	3.0% 13/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	5.1% 21/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Nail changes	2.6% 11/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	5.4% 22/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Rash/desquamation	10.5% 45/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	12.2% 50/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Hand-foot reaction	14.5% 62/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	13.7% 56/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Vomiting	20.6% 88/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	25.4% 104/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Anorexia	27.1% 116/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	30.5% 125/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Constipation	19.9% 85/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	22.0% 90/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Dehydration	5.4% 23/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	8.5% 35/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Diarrhea w/o prior colostomy	50.5% 216/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	52.0% 213/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Dyspepsia	5.1% 22/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	8.0% 33/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	22.9% 98/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	22.7% 93/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Muco/stomatitis (symptom) oral cavity	16.1% 69/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	18.3% 75/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Nausea	56.1% 240/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	56.8% 233/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Taste disturbance	15.7% 67/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	15.1% 62/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Rectum, hemorrhage	0.93% 4/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	6.6% 27/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Nose, hemorrhage	7.2% 31/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	26.1% 107/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypoalbuminemia	7.7% 33/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	7.1% 29/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Alkaline phosphatase increased	13.3% 57/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	7.8% 32/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Alanine aminotransferase increased	15.9% 68/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	11.7% 48/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Aspartate aminotransferase increased	20.6% 88/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	15.1% 62/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Blood bilirubin increased	5.1% 22/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	2.9% 12/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypocalcemia	6.5% 28/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	7.8% 32/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Investigations Creatinine increased	1.6% 7/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	5.6% 23/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyperglycemia	10.0% 43/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	11.7% 48/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypokalemia	8.4% 36/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	10.5% 43/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Renal and urinary disorders Proteinuria	1.6% 7/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	14.9% 61/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyponatremia	4.7% 20/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	6.8% 28/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Dizziness	6.1% 26/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	7.1% 29/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Neuropathy-sensory	77.3% 331/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	69.8% 286/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Neurologic-other	7.7% 33/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	6.6% 27/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Gastrointestinal disorders Abdomen, pain	9.1% 39/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	12.4% 51/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Nervous system disorders Head/headache	10.5% 45/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	18.5% 76/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Joint, pain	2.1% 9/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	6.8% 28/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Muscle, pain	8.6% 37/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	11.2% 46/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Cough	4.4% 19/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	6.3% 26/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.8% 29/428 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	12.2% 50/410 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.	— 0/0 • Assessed every 2 weeks while on treatment and for 30 days after the end of treatment, up to 10 years All patients received treatment at Step 2 and had adverse event data were included in the analysis of adverse events. Patients who underwent observation in Arm C did not receive any treatment, so no adverse event data were collected for these patients. All patients registered/randomized at Step 2 were included in the analysis of all-cause mortality.

Additional Information

Study Statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Email: eatrials@jimmy.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60