PHASE-II TRIAL OF TOPOTECAN IN MALIGNANT-MELANOMA

Topotecan (S-9-dimethyl-10-hydroxycamptothecin hydrochloride SKF 10486 4-A) is a semisynthetic analog of the alkaloid camptothecin and, simil ar to the parent compound, a potent inhibitor of topoisomerase I. The cytotoxicity induced by topotecan appears due to interference with the normal breakage reunion reaction of topoisomerase I leading to DNA da mage and cell death. Since preclinical studies of topotecan suggested antitumor activity against refractory solid tumors, a phase II trial o f the drug was initiated in melanoma patients with recurrent and/or me tastatic disease. Topotecan 1.5 mg/m(2) was given as a daily 30-min in fusion for 5 days and repeated every 21-28 days. Seventeen patients we re entered into the treatment program with all evaluable for toxicity but 1 patient, inevaluable for response. There were no objective respo nses. Toxicity was predominantly severe myelosuppression, which occurr ed in 12 of 17 (70%) patients. Topotecan in this dose and schedule is inactive in malignant melanoma.