The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: A prospective randomized phase III trial

N. Petrelli, H. O. Douglas, L. Herrera, D. Russell, D. M. Stablein, H. W. Bruckner, R. J. Mayer, R. Schinella, M. D. Green, F. M. Muggia, A. Megibow, E. S. Greenwald, R. M. Bukowski, J. Harris, B. Levin, E. A. Gaynor Loutfi, M. H. Kalser, J. S. Barkin

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Abstract

A total of 343 patients with previously untreated metastatic measurable colorectal carcinoma were studied to evaluate the impact on toxicity, response, and survival of leucovorin-moculated fluorouracil (5-FU). A maximally tolerated intravenous bolus loading course regimen of 5-FU alone (500 mg/m2 x 5 days every 4 weeks with 25 mg/m2 of 5-FU with 500 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest) and with a similar low-dose leucovorin regimen (600 mg/m2 of 5-FU with 25 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest). The dose-limiting toxicity for the two 5-FU and leucovorin regimens was gastrointestinal specifically diarrhea; severe diarrhea was seen frequently, and treatment-related toxicity was implicated in the demise of 11 of the patients (5%). Significant improvements in response rates were observed with a response rate of 33 of 109 (30.3%) on the high-dose leucovorin regimen (P < .01 v control); 13 of 107 (12.1%) on the 5-FU control; and 21 of 112 (18.8%) on the low-dose leucovorin regimen. A trend toward longer survival in the 5-FU plus high-dose leucovorin regimen was observed. In this study, leucovorin was shown to significantly enhance the therapeutic effect of 5-FU in metastatic colorectal carcinoma.

Original languageEnglish (US)
Pages (from-to)1419-1426
Number of pages8
JournalJournal of Clinical Oncology
Volume7
Issue number10
DOIs
StatePublished - Jan 1 1989
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Petrelli, N., Douglas, H. O., Herrera, L., Russell, D., Stablein, D. M., Bruckner, H. W., Mayer, R. J., Schinella, R., Green, M. D., Muggia, F. M., Megibow, A., Greenwald, E. S., Bukowski, R. M., Harris, J., Levin, B., Gaynor Loutfi, E. A., Kalser, M. H., & Barkin, J. S. (1989). The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: A prospective randomized phase III trial. Journal of Clinical Oncology, 7(10), 1419-1426. https://doi.org/10.1200/JCO.1989.7.10.1419