[Phase I clinical study of NK 171 (etoposide)]

A phase I clinical study of NK 171 (Etoposide), a semi-synthetic derivative of podophyllotoxin, administered by intravenous (i.v.) and oral (p.o.) routes was carried out in patients with malignant tumour who were resistant to standard therapy. As a starting dose of NK 171, 33mg/m2 (expressed as 1n) was administered for 5 consecutive days and the daily dose was increased step by step to a dose of 3.5n i.v. or 5n p.o. respectively. The dose-limiting factor of NK 171 given by the i.v. route was leukopenia and the nadir of leukopenia was observed about 2 weeks after the final day of drug administration in the case of both i.v. and p.o. routes. Recovery from leukopenia required about 3 and 2 weeks from the nadir in the case of i.v. and p.o. administration, respectively. Thrombocytopenia also occurred, but to a lower degree than that observed for leukopenia. A further side effect, alopecia, was observed in about half of the patients. From these results, it was concluded that the recommendable dose schedules of NK 171 for phase II clinical studies are 80-100mg/m2, i.v. and 110-130mg/m2, p.o., respectively, daily for 5 consecutive days and repeated every 4-5 weeks.