Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study

J Clin Oncol. 2001 Apr 15;19(8):2282-92. doi: 10.1200/JCO.2001.19.8.2282.

Abstract

Purpose: To compare the response rate, efficacy parameters, and toxicity profile of oral capecitabine with bolus intravenous (IV) fluorouracil plus leucovorin (5-FU/LV) as first-line treatment in patients with metastatic colorectal cancer.

Patients and methods: We prospectively randomized 605 patients to treatment with oral capecitabine for 14 days every 3 weeks or 5-FU/LV by rapid IV injection daily for 5 days in 4-week cycles.

Results: The overall objective tumor response rate among all randomized patients was significantly higher in the capecitabine group (24.8%) than in the 5-FU/LV group (15.5%; P =.005). In the capecitabine and 5-FU/LV groups, median times to disease progression were 4.3 and 4.7 months (log-rank P =.72), median times to treatment failure were 4.1 and 3.1 months (P =.19), and median overall survival times were 12.5 and 13.3 months (P =.974), respectively. Capecitabine, compared with bolus 5-FU/LV treatment, produced a significantly lower incidence (P <.0002) of diarrhea, stomatitis, nausea, and alopecia. Patients treated with capecitabine also displayed lower incidences of grade 3/4 stomatitis and grade 3/4 neutropenia (P <.0001) leading to significantly less neutropenic fever/sepsis. Grade 3 hand-foot syndrome (P <.00001) and grade 3/4 hyperbilirubinemia were the only toxicities more frequently associated with capecitabine than with 5-FU/LV treatment.

Conclusion: Oral capecitabine was more active than 5-FU/LV in the induction of objective tumor responses. Time to disease progression and survival were at least equivalent for capecitabine compared with the 5-FU/LV arm. Capecitabine also demonstrated clinically meaningful benefits over bolus 5-FU/LV in terms of tolerability.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Alopecia / chemically induced
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / adverse effects
  • Capecitabine
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Deoxycytidine / administration & dosage*
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Diarrhea / chemically induced
  • Disease Progression
  • Female
  • Fluorouracil / administration & dosage*
  • Fluorouracil / adverse effects
  • Humans
  • Injections, Intravenous
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Stomatitis / chemically induced
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antimetabolites, Antineoplastic
  • Deoxycytidine
  • Capecitabine
  • Leucovorin
  • Fluorouracil