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

Abstract

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 hand-foot 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.

• Authors: E Van Cutsem, C Twelves, J Cassidy, D Allman, E Bajetta, M Boyer, R Bugat, M Findlay, S Frings, M Jahn, J McKendrick, B Osterwalder, G Perez-Manga, R Rosso, P Rougier, W H Schmiegel, J F Seitz, P Thompson, J M Vieitez, C Weitzel, P Harper, Xeloda Colorectal Cancer Study Group
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 19 Issue 21 Pg. 4097-106 (Nov 01 2001) ISSN: 0732-183X [Print] United States
• PMID: 11689577 (Publication Type: Clinical Trial, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adenocarcinoma (drug therapy, secondary)
• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects, therapeutic use)
• Capecitabine
• Colorectal Neoplasms (drug therapy, pathology)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage, therapeutic use)
• Humans
• Infusions, Intravenous
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Prodrugs (administration & dosage, adverse effects, therapeutic use)
• Prospective Studies
• Survival Analysis