Antitumor activity of three second-line treatment combinations in patients with metastatic colorectal cancer after optimal 5-FU regimen failure: A randomised, multicentre phase II study

Background: We have investigated the efficacy, safety and quality of life profiles of three therapeutic combinations [irinotecan + leucovorin (LV)/5-fluorouracil (5-FU), oxaliplatin + LV/5-FU and irinotecan +oxaliplatin] in patients with metastatic colorectal cancer after failure of a 5-FU-based regimen, or whose disease had progressed within 6 months of the end of treatment. Patients and Methods: One hundred and one patients were randomised to receive either: (i) irinotecan 180 mg/m² on day 1 followed by an LV 200 mg/m² infusion, before a 5-FU 400 mg/m² bolus followed by a 5-FU 600 mg/m² infusion (LV5FU2 regimen), on days 1 and 2 every 2 weeks; (ii) oxaliplatin 85 mg/m² on day 1 followed by the LV5FU2 regimen on days 1 and 2 every 2 weeks; or (iii) oxaliplatin 85 mg/m² followed by irinotecan 200 mg/m², both on day 1 every 3 weeks. The primary end point was overall response rate (ORR). Results: The intention-to-treat ORRs were 11.4% [95% confidence interval (CI) 3.2-26.7), 21.2% (95% CI 9.0-38.9) and 15.2% (95% CI 5.1-31.9), respectively, in the three arms. Tumour growth control was ≥60% for all three combinations and overall survivals were 12.2 months (95% CI 9.2-16.0), 11.5 months (95% CI 9.0-14.1) and 11.0 months (95% CI 8.1-12.2), respectively. All patients were evaluable for safety. Main grade 3-4 toxicity was neutropenia (33 to 39% of patients). Conclusions: Thus, second-line treatment with irinotecan/LV5FU2, oxaliplatin/LV5FU2 or irinotecan/oxaliplatin, provides good tumour growth control and survival coupled with an acceptable safety profile.