Cisplatin and dichloromethotrexate: a pharmacologically rational combination.
Dichloromethotrexate (DCM), a dihalogenated analog of methotrexate (MTX), is a potent classic folate antagonist that is metabolized and excreted by the liver. It is not nephrotoxic nor are its pharmacokinetics significantly affected by changes in renal function. Therefore, the feasibility of administering a maximum tolerated dose of DCM in combination with high-dose ciplatin (CDDP) was investigated in patients with head and neck, bladder, or cervical cancer--three epithelial carcinomas known to be responsive to single-agent CDDP and MTX. The overall response rates in 24 evaluable patients with head and neck cancer, 21 evaluable patients with bladder cancer, and 22 evaluable patients with cervical cancer were 54%, 57%, and 50%, respectively. Complete response rates of 25%, 19%, and 36%, respectively, were observed. DCM can be administered on a weekly schedule at a maximum tolerated dose in combination with CDDP with tolerable side effects and without significant nephrotoxicity.
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
R B
RB
Natale
R H
RH
Wheeler
J A
JA
Roberts
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D002277:Carcinoma / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage*; D004341:Drug Evaluation; D005260:Female; D005493:Folic Acid Antagonists / Q000627:therapeutic use* / Q000633:toxicity; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
D005493:Folic Acid Antagonists; C004763:3',5'-dichloromethotrexate; D002945:Cisplatin; D008727:Methotrexate