Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer

PRIMARY OBJECTIVES:

I. Determine whether in advanced colorectal carcinoma patients who have been previously treated with 5-FU, the overall survival of patients treated with OXAL + 5-FU + CF followed by CPT-11 is equivalent to the survival of patients treated with CPT-11 followed by OXAL + 5-FU + CF.

SECONDARY OBJECTIVES:

I. Evaluation of time to tumor progression, time to treatment failure, toxicity of treatment, and overall response rate in patients treated with these two regimens.

II. To compare quality-of-life measurements patients treated with these two regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (ECOG 0-1 vs 2), primary indicator lesion (hepatic vs pulmonary vs other), age (less than 65 vs at least 65 years), alkaline phosphatase (less than 2 vs at least 2 times ULN), fluorouracil failure (adjuvant vs metastatic), and membership (intergroup vs expanded participation project). Patients are randomized to one of two treatment arms.

ARM I: Patients receive irinotecan IV over 90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on days 1 and 2, and fluorouracil IV bolus followed by IV infusion over 22 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.

Patients who experience progression or toxicity on the initial regimen may crossover to the other regimen. At least 3 weeks must elapse between regimens.

Quality of life is assessed at baseline, prior to each chemotherapy course, at crossover, and at the end of the study.

Patients are followed every 6 months for 3 years or until death.

Inclusion criteria

• Histologically or cytologically confirmed locally advanced, locally recurrent,or metastatic colorectal adenocarcinoma not curable by surgery or radiotherapy
• Progressive disease following:

• One prior fluorouracil based chemotherapy regimen for metastatic disease
• Failure during or within 6 months after fluorouracil based adjuvant therapy
• Measurable or evaluable disease
• No CNS metastases or carcinomatous meningitis
• Performance status - ECOG 0-2
• At least 12 weeks
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL (transfusion allowed)
• Bilirubin no greater than 1.5 mg/dL
• AST no greater than 5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 5 times ULN
• Creatinine no greater than 1.5 times ULN
• No uncontrolled high blood pressure
• No unstable angina
• No symptomatic congestive heart failure
• No myocardial infarction with the past 6 months
• No serious uncontrolled cardiac arrhythmias
• No New York Heart Association class III or IV heart disease
• No pleural effusion or ascites that cause respiratory compromise (e.g., dyspnea grade 2 or greater)
• No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Fluent in English
• No active or uncontrolled infection
• No other prior malignancy within the past 5 years, except:
• Adequately treated basal or squamous cell skin cancer
• Adequately treated noninvasive carcinomas
• No sensory neuropathy grade 2 or greater
• No uncontrolled colonic or small bowel disorders (greater than 3 loose stools daily)
• No concurrent sargramostim (GM-CSF)
• At least 4 weeks since prior chemotherapy and recovered
• No more than 1 prior chemotherapy regimen for advanced colorectal cancer
• No prior irinotecan or other camptothecin derivative (e.g., topotecan)
• No prior oxaliplatin
• No other concurrent investigational chemotherapy agents
• At least 4 weeks since prior major radiotherapy
• No prior radiotherapy to greater than 25% of bone marrow
• At least 4 weeks since prior major surgery and recovered
• At least 2 weeks since prior minor surgery and recovered