Combined irinotecan, oxaliplatin and 5-fluorouracil in patients with advanced colorectal cancer -: A feasibility pilot study

Objectives: To evaluate the feasibility and a possible activity range of combination irinotecan (CPT-11), oxaliplatin, and 5-FU in advanced colorectal cancer (ACC). Patients and Methods: A total of 53 patients (51 % chemoresistant) were treated. Twenty-eight received monthly intravenous oxaliplatin (120 mg/m(2)) and CPT-11 (250 Mg/M2) on day 1 and a course of 5-FU; these constituted the IR1250 group. Twenty-five received monthly intravenous oxaliplatin (120 Mg/M2), CPT-11 1 (300 Mg/M2) on day 1, and a course of 5-FU (IR1300 group). 5-FU administration was carried out as follows. Those with predominant hepatic disease (n = 32) received an intraarterial infusion of 5-FU (2,500 mg/day on days 1-4); these were the IA-FU group. The remaining 21 patients received intravenous 5-FU (2,600 Mg/M2 plus leucovorin 500 mg/m(2) on days 1 and 15); these constituted the IV-FUFOL group. Results: Intention-to-treat response rate was 54.7% (4 CR, 7.5%). Twelve patients (22.5%) had stable disease; only 4 (7.5%) progressed. Median progression-free and overall survivals were 10 and 18 months, respectively. One-year progression-free and overall survival rates were 44.3 and 67.4%, respectively. Grade 3-4 toxicities included diarrhea (45.3% of patients), neutropenia (52.8%), mucositis (13.2%), and emesis (11.3%). There were 3 treatment-related deaths (5.7%), all in the IA-FU/IRI300 subgroup. Severe adverse effects requiring chemotherapy dose adjustment were observed in 67.9% of the patients, with odds ratios 9.04-fold higher in the IA-FU/IRI300 group (95% Cl: 1.07-76.20) and 0.23-fold lower in the IV-FUFOL/IR1250 group (95% CI: 0.05-0.97). Conclusion: This combination seems to have substantial xicity was unacceptable in the with diarrhea and cytopenia constituting the dose-limiting side effects. Tolerance and efficacy profiles achieved with IV oxaliplatin (120 mg/m(2) day 1), IV CPT-11 (250 mg/m(2) day 1) and IV 5-FU 2.6 g/m(2) with IV leucovorin (500 mg/m(2) days 1 and 15) was favorable and deserves further investigation. Copyright (C) 2002 S. Karger AG, Basel.