Preliminary results of a phase II trial for the treatment of metastatic breast cancer with 5-fluorouracil and leucovorin

C. J. Allegra, B. A. Chabner, P. W. Sholar, C. Bagley, J. C. Drake, Marc E Lippman

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Scopus citations

Abstract

The active metabolite of FUra, 5-fluorodeoxyuridine monophosphate (5-FdUMP), requires the presence of reduced folates to form a covalent ternary complex with the target enzyme thymidylate synthase (TS). In vitro and in vivo studies have demonstrated a potentiation of the cytotoxic effects of FUra when combined with the reduced folate, leucovorin. We have applied this concept to the treatment of metastatic breast cancer in a phase II trial, as recent clinical studies on patients with colorectal carcinoma have suggested an enhanced efficacy for the combination of FUra plus leucovorin. Patients entered on the present study are undergoing treatment with a 5-day daily regimen of leucovorin (500 mg/m2, iv) followed by FUra (375 mg/m2, iv). Toxicity and response data are currently being collected on patients who have failed 'standard' combination regimens that included FUra. In patients with accessible tumor, serial biopsies are being obtained during treatment with the combination of FUra and leucovorin and during therapy with FUra alone to assess the degree of 5-FdUMP binding to the target enzyme, TS, in the presence and absence of exogenously administered leucovorin. Preliminary results from the biochemical studies suggest an enhanced saturation of TS by the fluorinated pyrimidine when administered with leucovorin.

Original languageEnglish
Title of host publicationNCI Monographs
Pages199-202
Number of pages4
Edition5
StatePublished - Dec 1 1987
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research

Cite this

Allegra, C. J., Chabner, B. A., Sholar, P. W., Bagley, C., Drake, J. C., & Lippman, M. E. (1987). Preliminary results of a phase II trial for the treatment of metastatic breast cancer with 5-fluorouracil and leucovorin. In NCI Monographs (5 ed., pp. 199-202)