Capecitabine, an oral fluoropyrimidine carbamate with substantial activityin advanced colorectal cancer: Results of a randomized phase II study

Purpose: to evaluate in patients with advanced colorectal cancer (CRC) thre e treatment regimens of oral capecitabine in order to select the most appro priate regimen for resting in phase III. Patients and Methods: Three capecitabine schedules were evaluated in a rand omized phase II design: arm A, 1,331 mg/m(2)/d bid continuously; arm B, 2,5 10 mg/m(2)/d bid intermittently (2 weeks on/1 week off); and arm C, 1,657 m g/m(2)/d plus oral leucovorin 60 mg/d bid intermittently (2 weeks on/1 week off). Results: One hundred nine patients were randomized; 39 patients were assess able for efficacy in arm A, 34 in arm B, and 35 in arm C, Patient character istics were balanced in the arms. Confirmed tumor responses (partial respon se [PR] + complete response [CR]) were reported for eight patients with two CRs (21%; 95% confidence interval [CI], 9% to 36%) in arm A, eight patient s with one CR (24%; 95% CI, 11% to 41%) in arm B, and eight patients with t wo CRs (23%; 95% CI, 10% to 40%) in arm C. Median times to progression (TTP ) in arms A, B, and C were 127, 230, and 165 days, respectively. Overall, m ore toxicity was seen with capecitabine plus leucovorin, particularly diarr hea and hand-foot syndrome. There was no grade 3 or 4 marrow toxicity, Conclusion: Capecitabine offers a new, effective treatment option as an ora l single agent in advanced CRC, Promising overall response rates were repor ted for all three regimens. The addition of leucovorin to the intermittent regimen had no marked effect on tumor response or median TTP. The intermitt ent single-agent capecitabine schedule is proposed for phase III evaluation , based on considerations of toxicity, dose-intensity, response rate, and T TP, (C) 2000 by American Society of Clinical Oncology.