Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: Results of a large phase III study

Purpose: To compare the efficacy and safety of orally administered capecita bine (Xeloda; Roche Laboratories, Inc, Nutley, NJ), a novel fluoropyrimidin e carbamate designed to mimic continuous fluorouracil (5-FU) infusion but w ith preferential activation at the tumor site, with that of intravenous (IV ) 5-FU plus leucovorin (5-FU/LV) as first-line treatment for metastatic col orectal cancer. Patients and Methods: We prospectively randomized 602 patients to treatment with capecitabine 1,250 mg/m(2) administered twice daily days I to 14 ever y 3 weeks, or to the 4-weekly Mayo Clinic regimen (5-FU/LV) until disease p rogression 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 ty pical of fluoropyrimidines. However, capecitabine led to significantly lowe r incidences (P < .00001) of stomatitis and alopecia, but a higher incidenc e of cutaneous hand-foot syndrome (P < .00001). Capecitabine also resulted in lower incidences (P < .00001) of grade 3/4 stomatitis and neutropenia, l eading to a lower incidence of grade 3/4 neutropenic fever and sepsis. Only grade 3 hand-foot syndrome (P < .00001) and uncomplicated grade 3/4 hyperb ilirubinemia (P < .0001) were reported more frequently with capecitabine. Conclusion: Oral capecitabine achieved an at least equivalent efficacy comp ared with IV 5-FU/LV. Capecitabine demonstrated clinically meaningful safet y advantages and the convenience of an oral agent. (C) 2001 by American Soc iety of Clinical Oncology.