Phase II trial of oral methotrexate and dipyridamole in colorectal carcinoma

S. Wadler, M. Subar, M. D. Green, P. H. Wiernik, F. M. Muggia

Research output: Contribution to journalArticlepeer-review


We have employed a rationally designed combination attempting to biochemically modulate the cytotoxicity of methotrexate (MTX), an inhibitor of de novo purine and pyrimidine synthesis, by dipyridamole (DP), a noncytotoxic modulator which blocks cellular transport of preformed nucleosides, in the treatment of 27 patients with advanced colorectal carcinoma. Doses and schedule determined from a previous phase I pharmacokinetic study were MTX at 2.5 mg orally twice a day for 4 days to begin concurrently with DP, at 75 mg orally four times daily for 8 days. One partial response was achieved in a patients who had progressed on a previous regimen of leucovorin and 5-fluorouracil. The major toxic effects observed were myelosuppression and stomatitis. Lack of efficacy could be interpreted to reflect incomplete modulation. Therefore, studies employing continuous iv infusion of DP concurrent with or a loading schedule of DP prior to administration of MTX may be required to provide adequate evaluation of such biochemically directed strategies.

Original languageEnglish
Pages (from-to)821-824
Number of pages4
JournalCancer Treatment Reports
Issue number9
StatePublished - 1987
Externally publishedYes


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