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A phase I study of N -palmitoyl-1-β- d-arabinofuranosylcytosine (PLAC) was conducted in 88 patients; 36 with solid tumors and 52 with hematological malignancies, using 2 different schedules. Schedule 1 employed a single oral administration and Schedule 2, 5-day consecutive daily oral administration. In Schedule 1, the daily dose was initiated with 1 mg kg which was escalated up to 24 mg kg according to the modified Fibonacci's method. Side effects included nausea, vomiting and skin rashes, but myelosuppression was not seen within this dose range. In Schedule 2, the daily dose was started with 1 mg kg which was escalated up to 24 mg kg. Major side effects were nausea, vomiting and amorexia, and mild myelosuppression was noted at 12 mg kg or more. The dose-limiting toxicity was gastrointestinal toxicity, which appeared at 3.3 mg kg or more and became frequent at 7 mg kg or more. Pharmacokinetic study revealed that the plasma concentrations of PLAC and ara-C, obtained by the oral intake of 3.3 mg kg or more of PLAC, were sufficient for these compounds to exert cytotoxic effects on various human leukemia cells in vitro. Based on these observations and plausible mechanism of action of PLAC, further clinical study should be carried out in a treatment schedule of considerably prolonged administration period with 3.3-6 mg kg day of PLAC. [ABSTRACT FROM AUTHOR]