Springer Online Journal Archives 1860-2000
Summary VP16-213 is a semi-synthetic derivative of podophyllotoxin. Preclinical trials have indicated a marked schedule dependency in the L1210 system suggestive of an advantage to short-cycle times and divided dose regimens. Seventy-seven patients with advanced breast carcinoma were studied. All patients had failed conventional combination chemotherapy (median prior chemotherapy: 23 months). All had prior Adriamycin and more than half had prior exposure to vinca alkaloids. The patients were randomly allocated to either: 1) intermittent bolus —50–70 mg/m2/day over 1 h daily for 5 days (39 patients), or 2) infusion — 50–70 mg/m2/day as a continuous infusion for 5 days (38 patients). In the intermittent group, three patients were inevaluable (early death) and one was lost to follow-up. In the infusion group, four patients were inevaluable (early death), two were lost to follow-up and one refused further treatment. In the intermittent group of 35 evaluable patients, five (14%) achieved partial remission, three (9%) had responses less than partial, six (17%) had stable disease, and 21 (60%) had progressive disease. In the infusion group of 31 evaluable patients, one (3%) achieved complete remission, three (10%) achieved partial remission, three (10%) had responses less than partial, five (16%) had stable disease and 19 (61%) had progressive disease. Principle toxicity observed was myelosuppression, which was severe (granulocytes 〈1,000) in approximately 50% with nadirs occuring at about day 12. Recovery was rarely prolonged beyond day 20. Nausea and vomiting were moderate with the intermittent schedule and almost absent with the infusion schedule. One patient in the intermittent group developed an anaphylactoid reaction requiring discontinuation of the drug. Congestive heart failure was precipitated by the fluid load in five patients on the infusion schedule. VP16-213 has significant antitumor activity in refractory breastcarcinoma and merits further evaluation. The infusion schedule showed no advantage over the intermittent schedule of this study.
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