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.
AuthorsA Harstrick, U Vanhoefer, A Heidemann, H Druyen, H Wilke, S Seeber
JournalAnti-cancer drugs (Anticancer Drugs) Vol. 8 Issue 4 Pg. 391-5 (Apr 1997) ISSN: 0959-4973 [Print] ENGLAND
PMID9180394 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cyclobutanes
  • Organoplatinum Compounds
  • lobaplatin
  • Cisplatin
  • Fluorouracil
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Carcinoma, Non-Small-Cell Lung (drug therapy)
  • Cisplatin (administration & dosage)
  • Cyclobutanes (administration & dosage)
  • Drug Interactions
  • Drug Screening Assays, Antitumor
  • Female
  • Fluorouracil (administration & dosage)
  • Humans
  • Lung Neoplasms (drug therapy)
  • Organoplatinum Compounds (administration & dosage)
  • Ovarian Neoplasms (drug therapy)
  • Tumor Cells, Cultured

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