Treatment of advanced colorectal carcinoma with oxaliplatin and capecitabine - A phase II trial

BACKGROUND. The current study was designed to evaluate the antitumor activity and toxicity of capecitabine and oxaliplatin in previously untreated patients with advanced colorectal carcinoma. The primary endpoint of the study was to determine the objective response rate, and a secondary endpoint was to measure the time to disease progression. METHODS. A 2-stage trial was planned with an accrual goal of 35 patients. The treatment included oxaliplatin given at a dose of 130 mg/m(2) on Day 1 of each 3-week cycle. Initially, capecitabine at a dose of 2000 mg/m(2)/day in 2 divided doses was given on Days 1-14 of each cycle, but this was reduced to a dose of 1500 mg/m(2)/day because of toxicity. Patients were followed by computed tomography scans every two cycles to evaluate treatment response, and toxicity was monitored. RESULTS. The first 13 patients on the trial received the higher dose of capecitabine. Although 5 responses (38.5%) were noted, 5 patients were hospitalized with diarrhea and dehydration. This toxicity led to a decrease in the dose of capecitabine to 1500 mg/m(2)/day and an additional 35 patients were treated. At the lower dose, the partial response rate was 37.1% (95% confidence interval [95% CI], 21.5-55.1%). The estimated median progression-free survival was 6.9 months (95% Cl, 4.4-8.2 months). At the lower dose, four patients were hospitalized with diarrhea/dehydration (with one death reported), one with febrile neutropenia, and one with ventricular fibrillation. Overall, Grade (according to version 2.0 of the National Cancer Institute Common Toxicity Criteria) 3-4 diarrhea was reported to develop in 20% of those patients treated at the capecitabine dose of 1500 mg/m(2)/day compared with 62% of patients treated at the dose of 2000 mg/m(2)/day. CONCLUSIONS. The combination of oxaliplatin and capecitabine is an active and convenient regimen for the treatment of patients with advanced colorectal carcinoma and should be compared with other front-line regimens as therapy for disease.