PHASE-I TRIAL OF CISPLATIN, WR-2721, AND THE MURINE MONOCLONAL-ANTIBODY R24 IN PATIENTS WITH METASTATIC MELANOMA - CLINICAL AND BIOLOGIC EFFECTS

The therapeutic and biologic effects of murine monoclonal antibodies i n patients with malignancies have been widely investigated. Attempts t o enhance results by combining these, agents with cytotoxic drugs are now under study. A Phase I trial was performed to assess the toxicity and biologic effects of escalating doses of R24 (0-40 mg/m(2)/day 1-5, 8-12), an antibody that binds to the ganglioside G(D3) present on mel anoma cells, administered in combination with cisplatin (120 mg/m(2)) and WR-2721 (740 mg/m(2)) on day 1. Twenty-three patients with metasta tic malignant melanoma were treated and are evaluable. The true maximu m tolerated dose of R24 given as part of this combination was not reac hed. The toxicity of the regimen was moderate and included fever and u rticaria, which were attributed to R24. Severe but reversible renal fa ilure was noted in six patients in subsequent (two or more) treatment cycles, but when cisplatin was administered in 3% saline, this toxicit y was not seen. Responses were seen in 2 of 19 patients receiving all three agents and in 1 of 4 patients