Progress Report on a Phase II Trial of 5-Fluorouracil Plus Citrovorum Factor in Women with Metastatic Breast Cancer
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5-fluorouracil (FUra) has definite, albeit limited, antitumor activity against breast carcinoma (1). Inhibition of the enzyme, thymidylate synthetase (TS) by FdUMP, an active FUra metabolite, has been postulated as one biochemical mechanism for this antitumor activity (2). TS inhibition is markedly augmented by the presence of increased concentrations of the reduced folate, citrovorum factor (CF) (3). In 1985, preliminary information suggested that FUra plus CF resulted in more substantial activity against heavily pretreated metastatic breast cancer than would have been expected with FUra alone (4). This current study was designed 1) to study the antitumor activity and toxicity of FUra plus CF in metastatic breast cancer patients who had not been “heavily pretreated” with chemotherapy, 2) to examine the impact of this regimen on tumor TS activity, and 3) to correlate the degree of TS inhibition with clinical outcome. The protocol continues to accrue patients and this communication provides a progress report relating to antitumor activity and toxicity.
KeywordsMetastatic Breast Cancer Folinic Acid Metastatic Breast Cancer Patient Thymidylate Synthetase Skin Hyperpigmentation
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