Phase II study of the antifolate N10-propargyl-5,8-dideazafolic acid (CB 3717) in advanced breast cancer.
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.
Cantwell
B M
BM
University Department of Clinical Oncology, Newcastle General Hospital, Newcastle upon Tyne, U.K.
Macaulay
V
V
Harris
A L
AL
Kaye
S B
SB
Smith
I E
IE
Milsted
R A
RA
Calvert
A H
AH
D058186:Acute Kidney Injury / Q000139:chemically induced; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D056486:Chemical and Drug Induced Liver Injury; D004341:Drug Evaluation; D005260:Female; D005492:Folic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005493:Folic Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D011799:Quinazolines; C031662:CB 3717; D005492:Folic Acid; D013940:Thymidylate Synthase