Drug interactions of 5-fluorouracil with either cisplatin or lobaplatin--a new, clinically active platinum analog in established human cancer cell lines.
Lobaplatin [1,2-diaminomethylcyclobutane platinum(II)-lactate] is a new platinum compound which appears to possess incomplete cross-resistance to cisplatin and might have a favorable pattern of side effects. Since lobaplatin has activity in esophageal cancer, combination protocols with 5-fluorouracil (5-FU) are evaluated. In order to assess the mode of action of lobaplatin when combined with 5-FU, two human cancer cell lines were treated with various combinations of 5-FU given for either 2 or 24h and lobaplatin. Drug interactions were evaluated by isobologram analysis. Lobaplatin showed basically the same interaction pattern when combined with 5-FU as cisplatin. The combination of either platinum analog with a 24 h exposure to 5-FU was superior to a short-term 5-FU exposure. Furthermore, when 5-FU was given for 24 h, no additional effect of folinic acid was seen. From these data we conclude that cisplatin and lobaplatin show similar interactions with 5-FU. Protracted infusion schedules of 5-FU appear to be more active than bolus application.
Harstrick
A
A
Department of Internal Medicine, West German Cancer Center, Essen.
Vanhoefer
U
U
Heidemann
A
A
Druyen
H
H
Wilke
H
H
Seeber
S
S
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003503:Cyclobutanes / Q000008:administration & dosage; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D003503:Cyclobutanes; D009944:Organoplatinum Compounds; C066228:lobaplatin; D002945:Cisplatin; D005472:Fluorouracil