A phase I study of oral uracil/ftorafur (UFT) plus leucovorin and bis-acetato-ammine-dichloro-cyclohexylamine-platinum IV (JM-216) each given over 14 days every 28 days

Cancer Chemother Pharmacol. 1999;43(5):385-8. doi: 10.1007/s002800050911.


Purpose: To determine the feasibility, maximal tolerated doses, and response rates for a combined regimen of the platinum and 5-fluorouracil oral analogues bis-acetato-ammine-dichloro-cyclohexyl-amine platinum(IV) (JM-216) and uracil/ftorafur (UFT) coadministered as a 14 consecutive-day every 28-day schedule.

Methods: Of 20 patients enrolled in this investigation, 17 on the following dose escalation scheme were evaluable for toxicity and/or response: I UFT 300 mg/day, JM-216 5 mg/day (three patients), II UFT 300 mg/day, JM-216 10 mg/day (four patients), III UFT 300 mg/day, JM-216 20 mg/day (ten patients).

Results: All 17 evaluable patients were evaluable for toxicity. At dose level III dose-limiting nausea and emesis were observed in one patient despite maximal antiemetic support. Importantly, neurotoxicity and nephrotoxicity were not observed at the JM-216 dose levels examined in this study. This observation is consistent with results seen with single agent JM-216.

Conclusion: For JM-216 and UFT administered at 20 mg/day and 300 mg/day over 14 days, nausea and emesis were observed as the principal dose-limiting toxicities. These doses are considerably below the maximally tolerated doses of single agent JM-216 and UFT. Shorter administration schedules should be explored in an attempt to increase the dose intensity and minimize the toxicity of this combination oral regimen.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Administration, Oral
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Administration Schedule
  • Drug Combinations
  • Humans
  • Leucovorin / administration & dosage
  • Leucovorin / adverse effects
  • Neoplasms / drug therapy*
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Tegafur / administration & dosage
  • Tegafur / adverse effects
  • Treatment Outcome
  • Uracil / administration & dosage
  • Uracil / adverse effects
  • Vomiting / chemically induced


  • Drug Combinations
  • Organoplatinum Compounds
  • UFT(R) drug
  • Tegafur
  • Uracil
  • satraplatin
  • Leucovorin