O Ral C Apecitabine C Ompared W Ith I Ntravenous Fluorouracil P Lus L Eucovorin I N P Atients W Ith M Etastatic Colorectal C Ancer: R Esults O F a L Arge P Hase I II S Tudy

Purpose: To compare the efficacy and safety of orally administered capecitabine (Xeloda; Roche Laboratories, Inc, Nutley, NJ), a novel fluoropyrimidine carbamate designed to mimic continuous fluorouracil (5-FU) infusion but with preferential activation at the tumor site, with that of intravenous (IV) 5-FU plus leucovorin (5-FU/LV) as first-line treatment for metastatic colorectal cancer. Patients and Methods: We prospectively randomized 602 patients to treatment with capecitabine 1,250 mg/m 2 administered twice daily days 1 to 14 every 3 weeks, or to the 4-weekly Mayo Clinic regimen (5-FU/ LV) until disease progression or unacceptable toxicity. Results: The primary objective, to demonstrate at least equivalent response rates in the two treatment groups, was met. The overall response rate was 18.9% for capecitabine and 15.0% for 5-FU/LV. In the capecitabine and 5-FU/LV groups, respectively, median time to disease progression was 5.2 and 4.7 months (log-rank P .65); median time to treatment failure was 4.2 and 4.0 months (log-rank P .89); and median overall survival was 13.2 and 12.1 months (log-rank P .33). The toxicity profiles of both treatments were typical of fluoropyrimidines. However, capecitabine led to significantly lower incidences (P < .00001) of stomatitis and alopecia, but a higher incidence of cutaneous hand-foot syndrome (P < .00001). Capecitabine also resulted in lower incidences (P < .00001) of grade 3/4 stomatitis and neutropenia, leading to a lower incidence of grade 3/4 neutropenic fever and sepsis. Only grade 3 handfoot syndrome (P < .00001) and uncomplicated grade 3/4 hyperbilirubinemia (P < .0001) were reported more frequently with capecitabine. Conclusion: Oral capecitabine achieved an at least equivalent efficacy compared with IV 5-FU/LV. Capecitabine demonstrated clinically meaningful safety advantages and the convenience of an oral agent. J Clin Oncol 19:4097-4106. © 2001 by American Society of Clinical Oncology.