Sequential administration of 5-fluorouracil (5FU)/leucovorin (LV) followed by irinotecan (CPT-11) at relapse versus CPT-11 followed by 5-FU/LV in advanced colorectal carcinoma - A phase III randomized study

Purpose: The purpose of the present study was to evaluate the differences in the sequence of administration of 5-fluorouracil (5-FU)/leucovorin (LV) followed by irinotecan (CPT-11), or CPT-11 followed by 5-FU/LV in advanced colorectal cancer (ACC). Patients and Methods: Chemotherapy-naive patients with ACC were allocated to the following treatment groups: group A, a bolus of 20 mg/m(2) LV and 425 mg/m(2) 5-FU for 5 days until progression/relapse, and upon progression treatment with weekly CPT-11 (100 mg/m(2)), and group B, CPT-11 followed at progression/relapse by 5-FU/LV at the same doses and schedules as in group A. Results: 120 patients were randomized to receive one of the two treatment sequences and their pretreatment characteristics were equally balanced between treatment arms. No statistically significant difference was found in the objective response rate to CPT-11 (p = 0.45); partial response (PR) was 23.3% for group A patients and 33.3% for group B. Following documented progression and second line treatment there was a significant difference between the response rate in group A (23.3%) and group B where no patients were found to respond to second-line treatment with 5-FU/LV (p = 0.024). The median overall survival was 42.0 weeks (range, 36.6-47.4 weeks) for group A and 32.0 weeks (range, 28.2-35.8 weeks) for group B. The median time to progression for patients in group A following first-line 5-FU/LV was 18 weeks (range, 10-36 weeks) and 12 weeks (range, 10-16 weeks) for group B following first-line CPT-11 (p = 0.0005). Toxicity, according to WHO, was similar between groups. Conclusions: Treating patients with CPT-11 upon progression to 5-FU/LV treatment seems to be superior to the opposite sequence. We used these treatments as sequential monotherapies (at progression/relapse), and the best results are gained when 5-FU/LV is followed by CPT-11 at disease progression or relapse. Copyright (C) 2007 S. Karger AG, Basel.