Activity and safety of oxaliplatin with weekly 5-fluorouracil bolus and low-dose leucovorin as first-line treatment for advanced colorectal cancer.

This study was designed to evaluate the safety and tolerability of oxaliplatin combined with weekly boluses of 5-fluorouracil (5-FU) and low doses of leucovorin (LV) and to determine objective response, progression-free survival, and overall survival of patients with previously untreated advanced colorectal cancer. Seventy-nine patients enrolled in an observational, multicenter, prospective, open-label phase II study received intravenous (I.V.) infusions of oxaliplatin 85 mg/m2 over the course of 2 hours on days 1 and 14 and LV 20 mg/m2 over the course of 2 hours and 5-FU 500 mg/m2 as a bolus on days 1, 7, and 14 every 4 weeks until disease progression or unacceptable toxicity occurred. Seventy-nine patients were evaluable for safety, and data from 70 patients were used for efficacy analysis. The objective response rate was 51.4%. Complete responses occurred in 7 patients (10%), and partial responses occurred in 29 patients (41.4%). Disease control, defined as response or stable disease, was obtained in 56 of 70 patients (80%). The median duration of response was 8.34 weeks (range, 7.3-11.5 weeks). The median time to progression was 7.13 months (range, 6.28-7.72 months), and median overall survival time was 15 months (range, 12.32-18.37 months). Acute dose-limiting toxicities were grade 3/4 diarrhea and neutropenia, which occurred in 10.5% and 3.9% of patients, respectively. Among the 70 patients who experienced neurosensory toxicity, it was estimated that only 1.3% had grade 3 symptoms. Preliminary data showed that the regimen is at least as active as other regimens combining oxaliplatin and infusional schedules of 5-FU and might be more convenient for patients because it avoids the need for I.V. catheter implantation.