Trial Outcomes & Findings for Pemetrexed and/or Sunitinib as Second-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer (NCT NCT00698815)

Last Updated: 2022-02-08

Results Overview

The 18 week progression-free survival rate was defined as the proportion of patients that were alive and progression-free 18 weeks after registration into the study. Disease progression was assessed per modified RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, in either primary or nodal lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of new lesions. Kaplan-Meier estimate of 18-week progression-free survival was calculated.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

130 participants

Primary outcome timeframe

At 18 weeks

Results posted on

2022-02-08

Participant Flow

Between April 2008 and September 2011, 130 participants were recruited.

Participant milestones

Participant milestones
Measure	Arm I (Pemetrexed) Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.	Arm II (Sunitinib) Patients receive sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.	Arm III (Pemetrexed and Sunitinib) Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.
Overall Study STARTED	42	47	41
Overall Study COMPLETED	32	33	31
Overall Study NOT COMPLETED	10	14	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Pemetrexed) Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.	Arm II (Sunitinib) Patients receive sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.	Arm III (Pemetrexed and Sunitinib) Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.
Overall Study Death	1	2	4
Overall Study Withdrawal by Subject	6	3	2
Overall Study MD discretion	2	7	2
Overall Study Did not receive protocol treatment	1	2	2

Baseline Characteristics

Pemetrexed and/or Sunitinib as Second-Line Therapy in Treating Patients With Stage IIIB or Stage IV Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Pemetrexed) n=42 Participants Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.	Arm II (Sunitinib) n=47 Participants Patients receive sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.	Arm III (Pemetrexed and Sunitinib) n=41 Participants Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.	Total n=130 Participants Total of all reporting groups
Age, Customized <60 years	16 participants n=5 Participants	15 participants n=7 Participants	15 participants n=5 Participants	46 participants n=4 Participants
Age, Customized 60-69 years	15 participants n=5 Participants	24 participants n=7 Participants	13 participants n=5 Participants	52 participants n=4 Participants
Age, Customized >=70 years	11 participants n=5 Participants	8 participants n=7 Participants	13 participants n=5 Participants	32 participants n=4 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	22 Participants n=7 Participants	19 Participants n=5 Participants	61 Participants n=4 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	25 Participants n=7 Participants	22 Participants n=5 Participants	69 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=5 Participants	47 Participants n=7 Participants	36 Participants n=5 Participants	122 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants	16 Participants n=4 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants	43 Participants n=7 Participants	32 Participants n=5 Participants	111 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	42 participants n=5 Participants	47 participants n=7 Participants	41 participants n=5 Participants	130 participants n=4 Participants
ECOG Performance Status 0	13 participants n=5 Participants	17 participants n=7 Participants	14 participants n=5 Participants	44 participants n=4 Participants
ECOG Performance Status 1	29 participants n=5 Participants	30 participants n=7 Participants	27 participants n=5 Participants	86 participants n=4 Participants
Stage (TMN) IIIB	5 participants n=5 Participants	8 participants n=7 Participants	3 participants n=5 Participants	16 participants n=4 Participants
Stage (TMN) IV	37 participants n=5 Participants	39 participants n=7 Participants	38 participants n=5 Participants	114 participants n=4 Participants

PRIMARY outcome

Timeframe: At 18 weeks

Outcome measures

Outcome measures
Measure	Arm I (Pemetrexed) n=42 Participants Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.	Arm II (Sunitinib) n=47 Participants Patients receive sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.	Arm III (Pemetrexed and Sunitinib) n=41 Participants Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.
18 Week Progression-free Survival (PFS) Rate	54 percentage of participants Interval 40.0 to 71.0	37 percentage of participants Interval 25.0 to 54.0	48 percentage of participants Interval 35.0 to 66.0

SECONDARY outcome

Timeframe: Time from randomization to disease progression and death of any cause, whichever comes first (up to 3 years)

PFS was defined as the time from randomization until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as in the primary outcome measure.

Outcome measures

Outcome measures
Measure	Arm I (Pemetrexed) n=42 Participants Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.	Arm II (Sunitinib) n=47 Participants Patients receive sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.	Arm III (Pemetrexed and Sunitinib) n=41 Participants Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.
PFS	4.9 months Interval 2.1 to 8.8	3.3 months Interval 2.3 to 4.2	3.7 months Interval 2.5 to 5.8

SECONDARY outcome

Timeframe: Duration of treatment (up to 3 years)

The proportion of patients who respond (completely or partially) to each combination regimen will be estimated. An exact binomial confidence interval will be computed for these estimates. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions.

Outcome measures

Outcome measures
Measure	Arm I (Pemetrexed) n=42 Participants Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.	Arm II (Sunitinib) n=47 Participants Patients receive sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.	Arm III (Pemetrexed and Sunitinib) n=41 Participants Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.
Overall Response Rate	14 percentage of participants Interval 5.0 to 29.0	17 percentage of participants Interval 8.0 to 31.0	22 percentage of participants Interval 11.0 to 38.0

SECONDARY outcome

Timeframe: Time from randomization to death (up to 3 years)

OS is defined as the time from patient randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Arm I (Pemetrexed) n=42 Participants Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.	Arm II (Sunitinib) n=47 Participants Patients receive sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.	Arm III (Pemetrexed and Sunitinib) n=41 Participants Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.
Overall Survival (OS)	10.5 months Interval 8.3 to 20.2	8.0 months Interval 6.8 to 13.5	6.7 months Interval 4.1 to 10.1

Adverse Events

Arm I (Pemetrexed)

Serious events: 13 serious events

Other events: 39 other events

Deaths: 0 deaths

Arm II (Sunitinib)

Serious events: 19 serious events

Other events: 43 other events

Deaths: 0 deaths

Arm III (Pemetrexed and Sunitinib)

Serious events: 21 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Rebecca S. Heist, MD

Massachusetts General Hospital

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Arm I (Pemetrexed) n=41 participants at risk Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.	Arm II (Sunitinib) n=44 participants at risk Patients receive sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.	Arm III (Pemetrexed and Sunitinib) n=39 participants at risk Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.
Investigations Platelet count decreased	7.3% 3/41 • Number of events 6 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	13.6% 6/44 • Number of events 6 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	30.8% 12/39 • Number of events 14 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Investigations Weight gain	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Investigations Weight loss	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Anorexia	9.8% 4/41 • Number of events 5 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	11.4% 5/44 • Number of events 7 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	20.5% 8/39 • Number of events 8 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Blood bicarbonate decreased	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Blood glucose increased	4.9% 2/41 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	17.9% 7/39 • Number of events 9 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Dehydration	2.4% 1/41 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	10.3% 4/39 • Number of events 5 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Serum albumin decreased	4.9% 2/41 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	15.9% 7/44 • Number of events 8 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	20.5% 8/39 • Number of events 9 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Serum calcium decreased	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	9.1% 4/44 • Number of events 4 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	15.4% 6/39 • Number of events 9 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Serum calcium increased	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Serum magnesium decreased	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	7.7% 3/39 • Number of events 4 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Serum phosphate decreased	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Serum potassium decreased	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	6.8% 3/44 • Number of events 3 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	10.3% 4/39 • Number of events 4 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Serum potassium increased	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Serum sodium decreased	2.4% 1/41 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	13.6% 6/44 • Number of events 6 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	12.8% 5/39 • Number of events 7 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Metabolism and nutrition disorders Serum triglycerides increased	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Musculoskeletal and connective tissue disorders Arthralgia	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 3 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	5.1% 2/39 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Musculoskeletal and connective tissue disorders Back pain	4.9% 2/41 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Musculoskeletal and connective tissue disorders Bone pain	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Musculoskeletal and connective tissue disorders Muscle weakness	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	7.7% 3/39 • Number of events 3 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	5.1% 2/39 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Nervous system disorders Ataxia	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Nervous system disorders Cognitive disturbance	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Nervous system disorders Dizziness	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Nervous system disorders Dysgeusia	4.9% 2/41 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	5.1% 2/39 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Nervous system disorders Facial nerve disorder	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Nervous system disorders Headache	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	5.1% 2/39 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Nervous system disorders Ischemia cerebrovascular	4.9% 2/41 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Nervous system disorders Neurological disorder NOS	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Nervous system disorders Peripheral motor neuropathy	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Nervous system disorders Peripheral sensory neuropathy	7.3% 3/41 • Number of events 4 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	5.1% 2/39 • Number of events 3 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Nervous system disorders Seizure	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Nervous system disorders Tremor	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Psychiatric disorders Anxiety	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Psychiatric disorders Confusion	4.9% 2/41 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Psychiatric disorders Depression	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Psychiatric disorders Insomnia	4.9% 2/41 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 3 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	5.1% 2/39 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).

Other adverse events
Measure	Arm I (Pemetrexed) n=41 participants at risk Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive sunitinib malate as in Arm II as third-line therapy.	Arm II (Sunitinib) n=44 participants at risk Patients receive sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive pemetrexed disodium as in Arm I as third-line therapy.	Arm III (Pemetrexed and Sunitinib) n=39 participants at risk Patients receive pemetrexed disodium 500 mg/m\^2 IV over 10 minutes on day 1 and sunitinib malate at 37.5 mg PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with documented disease progression may then receive third-line therapy at the discretion of the treating physician.
Gastrointestinal disorders Abdominal pain	9.8% 4/41 • Number of events 7 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	6.8% 3/44 • Number of events 7 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	7.7% 3/39 • Number of events 6 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Anal exam abnormal	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Colonic hemorrhage	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Blood and lymphatic system disorders Anemia	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Blood and lymphatic system disorders Blood disorder	2.4% 1/41 • Number of events 4 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Blood and lymphatic system disorders Hemoglobin decreased	58.5% 24/41 • Number of events 66 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	40.9% 18/44 • Number of events 52 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	56.4% 22/39 • Number of events 66 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Blood and lymphatic system disorders Hemolysis	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Blood and lymphatic system disorders Lymphatic disorder	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Cardiac disorders Arrhythmia	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Cardiac disorders Cardiac pain	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Cardiac disorders Edema	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Cardiac disorders Myocardial ischemia	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	5.1% 2/39 • Number of events 3 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Cardiac disorders Sinus bradycardia	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Ear and labyrinth disorders Ear pain	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 12 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Ear and labyrinth disorders Hearing impaired	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Ear and labyrinth disorders Tinnitus	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Endocrine disorders Adrenal insufficiency	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Endocrine disorders Hyperthyroidism	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Endocrine disorders Hypothyroidism	4.9% 2/41 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 9 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	5.1% 2/39 • Number of events 3 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Eye disorders Blurred vision	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Eye disorders Dry eye syndrome	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 4 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Eye disorders Eye disorder	7.3% 3/41 • Number of events 3 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Eye disorders Optic nerve edema	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Eye disorders Vision blurred	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 14 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Eye disorders Watering eyes	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 13 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Abdominal distension	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Constipation	22.0% 9/41 • Number of events 21 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	13.6% 6/44 • Number of events 11 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	5.1% 2/39 • Number of events 4 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Diarrhea	24.4% 10/41 • Number of events 25 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	36.4% 16/44 • Number of events 65 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	25.6% 10/39 • Number of events 23 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Dry mouth	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	11.4% 5/44 • Number of events 27 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 4 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Dyspepsia	7.3% 3/41 • Number of events 17 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	18.2% 8/44 • Number of events 22 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	7.7% 3/39 • Number of events 4 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Dysphagia	4.9% 2/41 • Number of events 9 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	4.5% 2/44 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Ear, nose and throat examination abnormal	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Flatulence	2.4% 1/41 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 2 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Gingival pain	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.3% 1/44 • Number of events 4 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Hemorrhoids	4.9% 2/41 • Number of events 4 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.00% 0/41 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	0.00% 0/44 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	2.6% 1/39 • Number of events 1 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Mucositis oral	7.3% 3/41 • Number of events 13 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	36.4% 16/44 • Number of events 29 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	25.6% 10/39 • Number of events 15 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).
Gastrointestinal disorders Nausea	29.3% 12/41 • Number of events 54 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	40.9% 18/44 • Number of events 39 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).	41.0% 16/39 • Number of events 35 Adverse events were evaluated for 124 participants (41, 44 and 39 on Arm I, II and III, respectively).