Since there appears to be a schedule dose relationship for VP16-213, the current dose seeking study of 5 day continuous infusion was initiated. Patients not candidates for other treatments were started at 75 mg/m2/day X 5. Eight patients had prior chemotherapy, eight had radiotherapy plus chemotherapy and one patient had prior interferon. The median age was 53 (range 23-65) and the median performance status was 60 (range 50-90). Seventeen patients received 20 courses; two at 75 mg/m2/day, seven at 100 mg/m2/day, ten at 125 mg/m2/day, and six at 150 mg/m2/day. The major toxicity was hematologic and median WBC count nadirs (ranges) were respectively: 3.5 (2.3-4.7) X 10(3)/microliters, 1.6 (0.2-3.4) X 10(3)/microliters, 2.4 (0.1-3.6) X 10(3)/microliters, 0.4 ( less than 0.1-0.7) 10(3)/microliters. Platelet count nadirs were respectively: 150, 78 (20-189), 138 (26-326), 16 (9-88) X 10(3)/microliters. The median days to WBC nadir and recovery and did not vary with dose and were 15 (9-21) and 24 (19-38) respectively. Median days to platelet count nadir were 12 (10-29) the recovery 24 (20-38) and did not vary with dose. Non-hematologic toxicities included mild nausea and vomiting, mild mucositis on six courses, diarrhea with two courses and fever during granulocytopenia during seven courses. Three patients manifested evidence of myocardial diseases two with infarction and one with congestive failure during treatment. Two patients showed objective evidence of tumor regression, one patient with seminoma and one patient with renal cell carcinoma. The latter response was short. The current studies demonstrate that high dose continuous infusion VP16-213 is tolerable with acceptable toxicity using doses up to 125 mg/m2/day (625 mg/m2 over 5 days).