Trial Outcomes & Findings for Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer (NCT NCT00316888)

Last Updated: 2023-06-29

Results Overview

Local failure was defined as progression/relapse of disease in the anal canal and/or regional organs and/or regional lymph nodes after completion of protocol therapy, or progression during protocol therapy. Lost to follow-up and death (regardless of cause of death) prior to 3 years were also considered as local failures. For the calculation of local failure rate at 3 years, patients were classified into two groups (ie, coded as binary variable): failure (patients with local failure events prior to 3 years) vs. no failure (patients who still alive and had no local failure at 3 years). The binomial proportion and its exact two-sided 80% confidence interval (CI) were used to estimate it.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3

Results posted on

2023-06-29

Participant Flow

This study was activated on January 19, 2007 and accrued its first patient on February 28, 2007, 28 patients were enrolled to arm I (closed to accrual on 11/3/2008) and 35 patients were enrolled to arm II (open to accrual on 8/18/2009).

Participant milestones

Participant milestones
Measure	Arm I (Closed to Accrual as of 11/3/2008) Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Arm II (Open to Accrual on 8/18/2009) Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
Overall Study STARTED	28	35
Overall Study Eligible	28	35
Overall Study Treated	28	34
Overall Study Started Induction Chemotherapy	28	0
Overall Study Started Chemo+Radiation+Cetuximab	27	34
Overall Study COMPLETED	22	27
Overall Study NOT COMPLETED	6	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Closed to Accrual as of 11/3/2008) Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Arm II (Open to Accrual on 8/18/2009) Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
Overall Study Adverse Event	4	5
Overall Study Withdrawal by Subject	2	2
Overall Study Not start protocol therapy	0	1

Baseline Characteristics

Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Closed to Accrual as of 11/3/2008) n=27 Participants Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Arm II (Open to Accrual on 8/18/2009) n=34 Participants Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Total n=61 Participants Total of all reporting groups
Age, Continuous	56 years n=5 Participants	56 years n=7 Participants	56 years n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	28 Participants n=7 Participants	49 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3

Population: eligible and treated patients

Outcome measures

Outcome measures
Measure	Arm I (Closed to Accrual as of 11/3/2008) n=27 Participants Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Arm II (Open to Accrual on 8/18/2009) n=34 Participants Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
Local Failure Rate at 3 Years	0.259 proportion of participants Interval 0.15 to 0.397	0.353 proportion of participants Interval 0.243 to 0.477

SECONDARY outcome

Timeframe: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3

Population: eligible and treated patients

Overall survival (OS) is defined as time from registration to death from any cause. Patients alive are censored at the last contact date. Kaplan-Meier method was used to estimate the 3-year OS rate.

Outcome measures

Outcome measures
Measure	Arm I (Closed to Accrual as of 11/3/2008) n=27 Participants Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Arm II (Open to Accrual on 8/18/2009) n=34 Participants Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
3-year Overall Survival Rate	0.887 proportion of participants Interval 0.69 to 0.962	0.789 proportion of participants Interval 0.606 to 0.893

SECONDARY outcome

Timeframe: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3

Population: eligible and treated patients

Progression-free survival (PFS) was defined as time from registration to disease progression, relapse or death (whichever occurred first), censoring cases without PFS events at the date of last disease assessment documenting the patient was free of progression/relapse. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier method was used to estimate the 3-year PFS rate.

Outcome measures

Outcome measures
Measure	Arm I (Closed to Accrual as of 11/3/2008) n=27 Participants Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Arm II (Open to Accrual on 8/18/2009) n=34 Participants Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
3-year Progression-free Survival Rate	0.809 proportion of participants Interval 0.6 to 0.916	0.616 proportion of participants Interval 0.432 to 0.756

SECONDARY outcome

Timeframe: Tumor assessments were made at baseline, within 4 weeks of the completion of protocol treatment, then every 6 months if patient was 1-4 years from registration, yearly if patient was 5-10 years from registration until progression/relapse using the RECIST

Population: eligible and treated patients

Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all eligible and treated patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s).

Outcome measures

Outcome measures
Measure	Arm I (Closed to Accrual as of 11/3/2008) n=27 Participants Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Arm II (Open to Accrual on 8/18/2009) n=34 Participants Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
Objective Response Rate	0.630 proportion of participants Interval 0.424 to 0.806	0.647 proportion of participants Interval 0.465 to 0.802

SECONDARY outcome

Timeframe: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3

Population: eligible and treated patients who did not have permanent colostomy at study entry

Colostomy-free survival was defined as time from registration until time of colostomy or death without colostomy, censoring cases without colostomy at the data of last disease assessment documenting the patient was free of colostomy. Kaplan-Meier method was used to estimate the 3-year colostomy-free survival rate.

Outcome measures

Outcome measures
Measure	Arm I (Closed to Accrual as of 11/3/2008) n=27 Participants Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Arm II (Open to Accrual on 8/18/2009) n=34 Participants Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
3-year Colostomy-free Survival Rate	0.849 proportion of participants Interval 0.645 to 0.94	0.657 proportion of participants Interval 0.446 to 0.804

Adverse Events

Arm I (Closed to Accrual as of 11/3/2008)

Serious events: 26 serious events

Other events: 28 other events

Deaths: 0 deaths

Arm II (Open to Accrual on 8/18/2009)

Serious events: 29 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

ECOG-ACRIN statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Arm I (Closed to Accrual as of 11/3/2008) n=28 participants at risk Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Arm II (Open to Accrual on 8/18/2009) n=34 participants at risk Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Immune system disorders Allergic reaction	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Ear and labyrinth disorders Tinnitus	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Blood and lymphatic system disorders Anemia	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	14.7% 5/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations Leukocytes decreased	25.0% 7/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	41.2% 14/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations Lymphopenia	10.7% 3/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	17.6% 6/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations Neutrophils decreased	21.4% 6/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	50.0% 17/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations Platelets decreased	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	11.8% 4/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Cardiac disorders Left ventricular systolic dysfunction	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
General disorders Fatigue	21.4% 6/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	20.6% 7/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations Weight loss	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations INR increased	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations Activated partial thromboplastin time prolonged	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Skin and subcutaneous tissue disorders Rash/desquamation	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	5.9% 2/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Injury, poisoning and procedural complications Chemoradiation dermatitis	14.3% 4/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Injury, poisoning and procedural complications Radiation dermatitis	10.7% 3/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Skin and subcutaneous tissue disorders Ulceration	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Metabolism and nutrition disorders Anorexia	10.7% 3/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	20.6% 7/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Metabolism and nutrition disorders Dehydration	32.1% 9/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	32.4% 11/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Diarrhea w/o prior colostomy	53.6% 15/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	67.6% 23/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Dry mouth	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Malabsorption	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	8.8% 3/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Muco/stomatitis (symptom) esophagus	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Muco/stomatitis (symptom) oral cavity	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Respiratory, thoracic and mediastinal disorders Muco/stomatitis (symptom) pharynx	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Muco/stomatitis (symptom) rectum	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Nausea	25.0% 7/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	32.4% 11/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Vomiting	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	14.7% 5/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Rectum, hemorrhage	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Infections and infestations Infection w/ gr3-4 neut, lung	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Infections and infestations Infection Gr0-2 neut, bladder	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	5.9% 2/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Infections and infestations Infection Gr0-2 neut, rectum	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Infections and infestations Infection Gr0-2 neut, blood	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Infections and infestations Infection w/ unk ANC blood	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Metabolism and nutrition disorders Acidosis	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Metabolism and nutrition disorders Hypoalbuminemia	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	8.8% 3/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	5.9% 2/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.

Other adverse events
Measure	Arm I (Closed to Accrual as of 11/3/2008) n=28 participants at risk Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks	Arm II (Open to Accrual on 8/18/2009) n=34 participants at risk Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV cisplatin: Given IV fluorouracil: Given IV radiation therapy: Given once daily 5 days a week for 5 weeks
Ear and labyrinth disorders Tinnitus	10.7% 3/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Blood and lymphatic system disorders Anemia	39.3% 11/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	35.3% 12/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations Leukocytes decreased	53.6% 15/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	32.4% 11/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations Lymphopenia	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations Neutrophils decreased	39.3% 11/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	20.6% 7/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations Platelets decreased	39.3% 11/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	41.2% 14/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Cardiac disorders Sinus tachycardia	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	5.9% 2/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Vascular disorders Hypertension	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	8.8% 3/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Vascular disorders Hypotension	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	5.9% 2/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
General disorders Fatigue	82.1% 23/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	67.6% 23/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
General disorders Fever w/o neutropenia	14.3% 4/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	17.6% 6/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Psychiatric disorders Insomnia	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	11.8% 4/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations Weight loss	39.3% 11/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	73.5% 25/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Injury, poisoning and procedural complications Burn	14.3% 4/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	14.7% 5/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Skin and subcutaneous tissue disorders Dry skin	32.1% 9/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	20.6% 7/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Skin and subcutaneous tissue disorders Alopecia	32.1% 9/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	14.7% 5/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Skin and subcutaneous tissue disorders Pruritus/itching	10.7% 3/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	5.9% 2/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Skin and subcutaneous tissue disorders Rash/desquamation	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	5.9% 2/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	53.6% 15/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	55.9% 19/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Injury, poisoning and procedural complications Chemoradiation dermatitis	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	2.9% 1/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Injury, poisoning and procedural complications Radiation dermatitis	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	11.8% 4/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Skin and subcutaneous tissue disorders Hand-foot reaction	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Skin and subcutaneous tissue disorders Ulceration	14.3% 4/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	5.9% 2/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Metabolism and nutrition disorders Anorexia	53.6% 15/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	38.2% 13/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Constipation	25.0% 7/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	20.6% 7/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Metabolism and nutrition disorders Dehydration	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	14.7% 5/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Diarrhea w/o prior colostomy	53.6% 15/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	26.5% 9/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Dysphagia	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Dyspepsia	17.9% 5/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Muco/stomatitis by exam, oral cavity	42.9% 12/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	26.5% 9/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Respiratory, thoracic and mediastinal disorders Muco/stomatitis by exam, pharynx	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	5.9% 2/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Muco/stomatitis (symptom) oral cavity	32.1% 9/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	29.4% 10/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Nausea	82.1% 23/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	55.9% 19/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Proctitis	0.00% 0/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	5.9% 2/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Nervous system disorders Taste disturbance	28.6% 8/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	14.7% 5/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Vomiting	60.7% 17/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	38.2% 13/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Gastrointestinal disorders Rectum, hemorrhage	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	5.9% 2/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
General disorders Edema limb	7.1% 2/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	0.00% 0/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Metabolism and nutrition disorders Hypoalbuminemia	14.3% 4/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	26.5% 9/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
Investigations Alkaline phosphatase increased	3.6% 1/28 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.	11.8% 4/34 • Adverse events were assessed every cycle (1 cycle=28 days) while on treatment and for 30 days after the end of treatment. After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.