Phase II trial of topotecan in malignant melanoma.

Topotecan (S-9-dimethyl-10-hydroxycamptothecin hydrochloride SKF 104864-A) is a semisynthetic analog of the alkaloid camptothecin and, similar 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 damage and cell death. Since preclinical studies of topotecan suggested antitumor activity against refractory solid tumors, a phase II trial of the drug was initiated in melanoma patients with recurrent and/or metastatic disease. Topotecan 1.5 mg/m2 was given as a daily 30-min infusion for 5 days and repeated every 21-28 days. Seventeen patients were entered into the treatment program with all evaluablefor toxicity but 1 patient, inevaluable for response. There were no objective responses. Toxicity was predominantly severe myelosuppression, which occurred in 12 of 17 (70%) patients. Topotecan in this dose and schedule is inactive in malignant melanoma.