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.

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.

• Authors: P M Hoff, R Ansari, G Batist, J Cox, W Kocha, M Kuperminc, J Maroun, D Walde, C Weaver, E Harrison, H U Burger, B Osterwalder, A O Wong, R Wong
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 19 Issue 8 Pg. 2282-92 (Apr 15 2001) ISSN: 0732-183X [Print] United States
• PMID: 11304782 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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