Rationale for phase I study of UFT plus leucovorin and oral JM-216

Oncology (Williston Park). 1997 Sep;11(9 Suppl 10):26-9.


Both cisplatin (Platinol) and fluorouracil (5-FU) have demonstrated single-agent clinical efficacy in a variety of solid neoplasms. The combination of these agents has revealed synergistic cytotoxicity in models in vitro and in vivo, which may explain the clinical effectiveness of 5-FU-cisplatin regimens. UFT (tegafur and uracil) and bis-aceto-ammine-dichloro-cyclohexyl-amine platinum(IV)(JM-216) are novel oral analogues of 5-FU and cisplatin, respectively. In preclinical models, JM-216 has demonstrated equivalent cytotoxicity to cisplatin, while phase I trials suggest its dose-limiting toxicity is myelosuppression. In contrast to cisplatin, JM-216 has not demonstrated significant neurotoxicity or nephrotoxicity. UFT has been used extensively in Japan, where phase II data suggest disease response rates similar to single-agent 5-FU in colorectal, gastric, and breast carcinomas. Combination studies of prolonged administration UFT and single-dose cisplatin have shown efficacy, but also significant hematologic toxicity. We propose a phase I study of UFT and JM-216 administered daily over 14 consecutive days with leucovorin (90 mg/d). Ease of administration and continuous drug exposure are potential advantages of this regimen. Several disease specific investigations may be warranted given demonstrated feasibility in this phase I study.

MeSH terms

  • Administration, Oral
  • Antidotes / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cisplatin / administration & dosage
  • Cisplatin / chemistry
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Drug Combinations
  • Drug Therapy, Combination
  • Humans
  • Leucovorin / therapeutic use*
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / chemistry
  • Tegafur / therapeutic use*
  • Uracil / therapeutic use*


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