Weekly irinotecan plus protracted venous fluorouracil infusion (WI-FI) in advanced colorectal cancer: a phase II study.

Background: Irinotecan (IRI) is a topoisomerase I inhibitor active as first- or second-line chemotherapy in advanced colorectal cancer (ACRC). Its combination with fluorouracil (FU) increases the response rate and prolongs survival. In order to identify a new effective and less toxic schedule of administration, we planned this phase II study with weekly IRI and protracted venous infusion of FU (WI-FI regimen). The primary endpoint was the objective response rate. Secondary aims were to detect toxicity, progression-free survival (PFS) and overall survival (OS) of patients (pts). Materials and Methods: On May 2000, a monoinstitutional study commenced with the following schedule of administration: IRI 80 mg/m 2 on days 1, 8, 15, 22, 29 plus a 28-day protracted venous infusion of FU 200 mg/m 2 /day. The treatment was repeated every 35 days. Cycles were administered until a maximum of 6 courses, disease progression or unacceptable toxicity. Results: By March 2005, 52 patients (30 males and 22 females) had entered the study. Their median age was 61.5 years and the median ECOG PS was 1. In total, 223 courses were administered (median 5 cycles/patient). Toxicity was low: neutropenia G3 and asthenia G3 were the most observed toxicities (5 pts each). No other grade 3-4 toxic side-effects were seen. Weekly IRI was interrupted in 11 pts, mostly related to problems with the central venous catheter. Following RECIST criteria, we observed 5 complete responses, 15 partial responses, 17 pts had stable disease, while in 15 disease progressed. The overall response rate was 38.5% and the disease control rate was 71.2%. Thirteen pts underwent surgical resection of their relapsing disease. The median PFS was 8.2 months and the median OS was 16.3 months. Conclusion: The WI-FI regimen is an active treatment with a good safety profile in patients with CRC. The low incidence of grade 3-4 toxicities justifies further evaluation of this combination.