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

Overview

Randomized phase III trial to compare the effectiveness of irinotecan with that of combination chemotherapy in treating patients who have advanced colorectal cancer that has not responded to previous treatment. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective for 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.