WR-2721 and high-dose cisplatin: an active combination in the treatment of metastatic melanoma.

Cisplatin, alone or in combination with other chemotherapeutic agents, is relatively inactive against metastatic melanoma. Prior trials have demonstrated partial response (PR) rates of less than 10% with cisplatin alone. WR-2721 is an organic thiophosphate compound, which in the animal model, selectively protects normal tissues against the toxicity of cisplatin chemotherapy. During the course of a phase I trial of WR-2721 and cisplatin, objective PRs were noted in patients with far advanced metastatic melanoma. These observations led us to perform a phase II trial of WR-2721 and cisplatin. Thirty-six patients received 128 courses of WR-2721 before cisplatin (60 to 150 mg/m2). All patients had progressive disease before treatment. Objective PRs were observed in 19 of 36 evaluable patients (53%). Three additional patients had minor responses (MRs). PRs occurred in 53% of patients with prior chemotherapy (ten of 19). Sites of responding metastases were subcutaneous disease (15 of 19 patients), lymph nodes (1...