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

Purpose: To determine the feasibility, maximal tolerated doses. and respons e rates for a combined regimen of the platinum and 5-fluorouracil oral anal ogues bis-acetato-ammine-dichloro-cyclohexyl-platinum(IV) (JM-216) and urac il/ftorafur (UFT) coadministered as a 14 consecutive-day every 28-day sched ule. Methods: Of 20 patients enrolled in this investigation, 17 on the foll owing 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-21 6 10 mg/day (four patients), III UFT 300 mg/day, JM-216 20 mg/day (ten pati ents). Rt str(ts: All 17 evalu able patients were evaluable for toxicity. A t dose level III, dose-limiting nausea and emesis were observed in one pati ent despite maximal antiemetic support. Importantly, neurotoxicity and neph rotoxicity were not observed at the JM-216 dose levels examined in this stu dy. This observation is consistent with results seen with single agent JM-2 16. 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 hose-limiti ng toxicities. These doses are considerably below the maximally tolerated d oses of single agent JM-216 and UFT. Shorter administration schedules shoul d be explored in an attempt to increase the dose intensity and minimize the toxicity of this combination oral regimen.