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Fifty-two patients with progressive advanced breast cancer were treated with the novel antifolate CB 3717 (N10-propargyl-5,8-dideazofolic acid) which inhibits thymidylate synthetase. Forty-six patients were pretreated with hormones, 43 with cytotoxic chemotherapy and 39 patients with both treatments. Eight of 48 patients (16.6%) evaluable for response had partial responses (confidence limits 7.4-30.2%, 95% confidence level) following CB 3717 administration. Liver function abnormalities, reversible in most cases, were the most commonest toxicities and were frequently accompanied by malaise. Severe renal failure occurred in eight patients, five of whom had had partial responses to CB 3717. This study shows the importance of thymidylate synthetase as a target for therapy but the clinical value of CB 3717 is limited by its hepatic and renal toxicities.

Original publication

DOI

10.1016/0277-5379(88)90307-0

Type

Journal article

Journal

Eur J Cancer Clin Oncol

Publication Date

04/1988

Volume

24

Pages

733 - 736

Keywords

Acute Kidney Injury, Adult, Aged, Antineoplastic Agents, Breast Neoplasms, Chemical and Drug Induced Liver Injury, Drug Evaluation, Female, Folic Acid, Folic Acid Antagonists, Humans, Middle Aged, Quinazolines, Thymidylate Synthase