[Phase I study of an oral administration of VP 16-213]

A phase I study of VP-16-213 oral capsule was performed in 25 patients with various malignant tumors refractory to standard treatments. Doses were escalated from 50 mg/d to 300 mg/d by a 5-day administration. Leukopenia was dose-related and nadirs at 200 mg/d, 250 mg/d and 300 mg/d were 2,000, 1,600 and 700/cmm respectively, reaching in about 2 weeks and approximately one week was required for recovery. Thrombocytopenia was also dose-related but generally less frequent and milder than leukopenia. Gastrointestinal toxicities such as anorexia, nausea and vomiting occurred in about 20% of patients but well tolerated; alopecia was observed in 40%. The result indicated that an optimal dose of oral VP-16-213 for phase II study was daily 200 mg/d (approximately 130 mg/m2) for 5 consecutive administration in 3-week intervals.