Trial Outcomes & Findings for Irinotecan and Docetaxel With or Without Cetuximab in Treating Patients With Metastatic Pancreatic Cancer (NCT NCT00042939)

Last Updated: 2023-07-06

Results Overview

Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= \>=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

94 participants

Primary outcome timeframe

Assessed every 12 weeks until progression

Results posted on

2023-07-06

Participant Flow

E8200 opened to accrual on 7/31/2003, accrued its first patient on 12/9/2003, and was suspended on 12/2/2004 for evaluation of response and toxicity. Arm B was reactivated on 7/12/2005 after meeting the response criteria; Arm A was reactivated on 11/23/2005. Arm B and Arm A closed to accrual on 4/17/2006 and 8/23/2006, respectively, after meeting the accrual goal.

Participant milestones

Participant milestones
Measure	Arm A: Irinotecan/Docetaxel Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.	Arm B: Irinotecan/Docetaxel/Cetuximab Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute. On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
Overall Study STARTED	48	46
Overall Study Treated	46	45
Overall Study Eligible and Began Protocol Therapy	44	43
Overall Study Patients With EGFR Results Available	30	31
Overall Study COMPLETED	24	25
Overall Study NOT COMPLETED	24	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Irinotecan/Docetaxel Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.	Arm B: Irinotecan/Docetaxel/Cetuximab Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute. On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
Overall Study Adverse Event	6	7
Overall Study Death	3	2
Overall Study Withdrawal by Subject	3	4
Overall Study Other disease	1	0
Overall Study Ineligible	2	2
Overall Study Deterioration of health	3	4
Overall Study QOL diminished	1	0
Overall Study Rising ca 19-9	1	0
Overall Study Patient non-compliance	1	0
Overall Study Still on treatment	1	0
Overall Study Treatment break > 4 weeks	0	1
Overall Study Did not start treatment	2	1

Baseline Characteristics

Irinotecan and Docetaxel With or Without Cetuximab in Treating Patients With Metastatic Pancreatic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Irinotecan/Docetaxel n=44 Participants Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.	Arm B: Irinotecan/Docetaxel/Cetuximab n=43 Participants Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute. On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.	Total n=87 Participants Total of all reporting groups
Age, Continuous	60.2 years n=99 Participants	60.6 years n=107 Participants	60.4 years n=206 Participants
Sex: Female, Male Female	20 Participants n=99 Participants	6 Participants n=107 Participants	26 Participants n=206 Participants
Sex: Female, Male Male	24 Participants n=99 Participants	37 Participants n=107 Participants	61 Participants n=206 Participants

PRIMARY outcome

Timeframe: Assessed every 12 weeks until progression

Population: Eligible patients who began treatment were included in the analysis.

Outcome measures

Outcome measures
Measure	Arm A: Irinotecan/Docetaxel n=44 Participants Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.	Arm B: Irinotecan/Docetaxel/Cetuximab n=43 Participants Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute. On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
Proportion of Patients With Objective Response Evaluated by RECIST (Solid Tumor Response Criteria)	0.045 Proportion of participants Interval 0.015 to 0.184	0.07 Proportion of participants Interval 0.024 to 0.198

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years and then every 6 months for 1 year

Population: Eligible patients who began treatment.

Progression-free survival was defined as the shorter of: 1. The time from registration to progression. or 2. The time from registration to death without documentation of progression given that the death occured within 4 months of the last disease assessment without progression (or registration, whichever is more recent). Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions.

Outcome measures

Outcome measures
Measure	Arm A: Irinotecan/Docetaxel n=44 Participants Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.	Arm B: Irinotecan/Docetaxel/Cetuximab n=43 Participants Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute. On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
Progression-free Survival	3.9 months Interval 2.4 to 5.0	4.5 months Interval 2.7 to 5.6

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years and then every 6 months for 1 year

Population: Eligible patients who began treatment.

Overall survival was defined as time from registration to death from any cause.

Outcome measures

Outcome measures
Measure	Arm A: Irinotecan/Docetaxel n=44 Participants Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.	Arm B: Irinotecan/Docetaxel/Cetuximab n=43 Participants Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute. On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
Overall Survival	6.5 months Interval 5.6 to 9.9	5.3 months Interval 4.5 to 9.4

SECONDARY outcome

Timeframe: Original tumor tissue samples submitted within one month of patient randomization

Population: Eligible and treated patients with EGFR stain results available.

EGFR expression was be evaluated by staining 5-micron paraffin sections of tumor biopsies with anti-EGFR clone 2-18C9 (DAKO Corporation, Carpinteria, CA) using an indirect immunoperoxidase technique according to the instructions provided by DAKO. In brief, this includes an antigen retrieval pretreatment, the blocking of endogenous peroxidase activity, incubation with anti-EGFR antibody or a negative reagent control, staining with a detection system, visualization, and coverslipping.

Outcome measures

Outcome measures
Measure	Arm A: Irinotecan/Docetaxel n=30 Participants Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.	Arm B: Irinotecan/Docetaxel/Cetuximab n=31 Participants Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute. On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
Epidermal Growth Factor Receptor (EGFR) Status Positive	29 participants	30 participants
Epidermal Growth Factor Receptor (EGFR) Status Negative	1 participants	1 participants

SECONDARY outcome

Timeframe: Assessed every 6 weeks while on treatment and for 30 days after the end of treatment

Population: Eligible and treated patients

To determine the rate of thromboembolic events in this population when prophylactic enoxaparin sodium is administered.

Outcome measures

Outcome measures
Measure	Arm A: Irinotecan/Docetaxel n=44 Participants Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.	Arm B: Irinotecan/Docetaxel/Cetuximab n=43 Participants Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute. On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
Proportion of Patients With Thromboembolic Events	0 Proportion of participants Interval 0.0 to 0.066	0.023 Proportion of participants Interval 0.001 to 0.106

Adverse Events

Arm A: Irinotecan/Docetaxel

Serious events: 35 serious events

Other events: 46 other events

Deaths: 0 deaths

Arm B: Irinotecan/Docetaxel/Cetuximab

Serious events: 36 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Statistician

ECOG Statistical Office

Phone: 617-632-3012

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A: Irinotecan/Docetaxel n=46 participants at risk Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.	Arm B: Irinotecan/Docetaxel/Cetuximab n=45 participants at risk Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute. On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
Immune system disorders Allergic Reaction	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Blood and lymphatic system disorders Anemia	8.7% 4/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	20.0% 9/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Leukopenia	26.1% 12/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	28.9% 13/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Lymphopenia	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Neutropenia	21.7% 10/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	28.9% 13/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Blood and lymphatic system disorders Transfusion: pRBCs	10.9% 5/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	4.4% 2/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Cardiac disorders Supraventricular Arrhythmias	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
General disorders Edema	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Vascular disorders Hypertension	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Vascular disorders Hypotension	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Cardiac disorders Pericardial Effusion/Pericarditis	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Vascular disorders Thrombosis/Embolism	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
General disorders Fatigue	21.7% 10/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	17.8% 8/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
General disorders Fever	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Weight Loss	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Blood and lymphatic system disorders DIC (Disseminated Intravascular Coagulation)	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Rash/Desquamation	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Skin-Other	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Anorexia	17.4% 8/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	8.9% 4/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Ascites	4.3% 2/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Constipation	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Ddhydration	8.7% 4/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	17.8% 8/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Dysphagia	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Gastritis	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Nausea	30.4% 14/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	20.0% 9/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Stomatitis	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Vomiting	13.0% 6/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	20.0% 9/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Diarrhea w/o Prior Colostomy	30.4% 14/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	46.7% 21/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders GI -Other	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Renal and urinary disorders Hematuria	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Melena/GI Bleeding	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	4.4% 2/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Alkaline Phosphatase Increased	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Bilirubin Increased	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations AST Increased	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations ALT Increased	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Blood and lymphatic system disorders Febrile Neutropenia	4.3% 2/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	4.4% 2/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Infections and infestations Infection w/ Grade 3 or 4 Neutropenia	4.3% 2/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Infections and infestations Infection w/ Unknown ANC	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Infections and infestations Infection w/o Neutropenia	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Infections and infestations Infection -Other	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyperglycemia	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	11.1% 5/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypocalcemia	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypokalemia	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyponatremia	4.3% 2/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypophosphatemia	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Muscle Weakness	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Dizziness/Lightheadedness	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Psychiatric disorders Insomnia	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Psychiatric disorders Anxiety/Agitation	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Neuropathy-Motor	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Syncope	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Eye disorders Conjunctivitis	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Abdominal Pain	4.3% 2/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	8.9% 4/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Myalgia	4.3% 2/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	0.00% 0/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
General disorders Pain-Other	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	4.4% 2/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
General disorders Syndromes-Other	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.

Measure	Arm A: Irinotecan/Docetaxel n=46 participants at risk Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. This constituted a cycle of treatment. Patients were evaluated after 2 cycles.	Arm B: Irinotecan/Docetaxel/Cetuximab n=45 participants at risk Patients received Cetuximab intravenously once a week for 6 weeks. On day 1 of cycle 1 only, an initial dose of 400 mg/m² (over 120 minutes) was administered. Thereafter, a once-a-week maintenance dose of 250 mg/m² (infused over 60 minutes), was given. The infusion rate never exceeded 5 ml/minute. On the day of the initial dose, the administration of Cetuximab was followed by the administration of docetaxel, after a 60-minute observation period. (The observation period was 30 minutes following maintenance doses.) Docetaxel was administered intravenously over 60 minutes at a dose of 35 mg/m². Docetaxel was diluted in 100-150 ml of infusion solution. After the completion of the docetaxel infusion, irinotecan was administered intravenously over 30 minutes at a dose of 50 mg/m². Chemotherapy was administered once a week (days 1, 8, 15, 22) for 4 consecutive weeks followed by 2 weeks rest. Cetuximab was administered once a week for 6 consecutive weeks. A cycle of treatment was 6 weeks.
Blood and lymphatic system disorders Anemia	87.0% 40/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	91.1% 41/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Leukopenia	71.7% 33/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	68.9% 31/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Neutropenia	52.2% 24/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	53.3% 24/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Thrombocytopenia	23.9% 11/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	13.3% 6/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
General disorders Edema	10.9% 5/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	11.1% 5/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Vascular disorders Hypotension	4.3% 2/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
General disorders Fatigue	69.6% 32/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	68.9% 31/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
General disorders Fever	13.0% 6/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	13.3% 6/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
General disorders Rigors/ Chills	15.2% 7/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Weight Loss	32.6% 15/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	35.6% 16/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Alopecia	54.3% 25/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	48.9% 22/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Dry Skin	8.7% 4/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	17.8% 8/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Nail Changes	17.4% 8/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	15.6% 7/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	8.9% 4/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Rash/Desquamation	8.7% 4/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	66.7% 30/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Skin and subcutaneous tissue disorders Skin-Other	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	22.2% 10/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Vascular disorders Hot Flashes	4.3% 2/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Anorexia	47.8% 22/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	55.6% 25/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Constipation	15.2% 7/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	20.0% 9/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Dehydration	15.2% 7/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Dyspepsia	10.9% 5/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	8.9% 4/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Mouth Dryness	8.7% 4/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	17.8% 8/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Nausea	50.0% 23/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	62.2% 28/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Stomatitis	17.4% 8/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	46.7% 21/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Taste Disturbance	13.0% 6/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	33.3% 15/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Vomiting	54.3% 25/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	44.4% 20/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Diarrhea w/o Prior Colostomy	58.7% 27/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	64.4% 29/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	15.6% 7/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Alkaline Phosphatase Increased	41.3% 19/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	46.7% 21/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Bilirubin Increased	13.0% 6/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	31.1% 14/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypoalbuminemia	8.7% 4/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	8.9% 4/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations AST Increased	13.0% 6/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	35.6% 16/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations ALT Increased	21.7% 10/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	51.1% 23/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Infections and infestations Infection w/o Neutropenia	10.9% 5/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	11.1% 5/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyperglycemia	15.2% 7/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	11.1% 5/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypocalcemia	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	11.1% 5/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypokalemia	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	8.9% 4/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	20.0% 9/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyponatremia	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	13.3% 6/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Muscle Weakness	13.0% 6/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Dizziness/Lightheadedness	4.3% 2/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	13.3% 6/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Psychiatric disorders Insomnia	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Psychiatric disorders Depression	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	6.7% 3/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Neuropathy-Motor	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	4.4% 2/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Neuropathy-Sensory	15.2% 7/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	26.7% 12/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Eye disorders Tearing	10.9% 5/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	4.4% 2/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Abdominal Pain	23.9% 11/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	15.6% 7/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Nervous system disorders Headache	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	4.4% 2/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Myalgia	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	2.2% 1/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.5% 3/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	20.0% 9/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Respiratory, thoracic and mediastinal disorders Hiccoughs	2.2% 1/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	11.1% 5/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.
Investigations Creatinine Increased	8.7% 4/46 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.	11.1% 5/45 • Assessed every 6 weeks while on treatment and for 30 days after the end of treatment.