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 in patients with malignancies have been widely investigated. Attempts to 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 melanoma cells, administered in combination with cisplatin (120 mg/m(2)) and WR-2721 (740 mg/m(2)) on day 1. Twenty-three patients with metastatic malignant melanoma were treated and are evaluable. The true maximum tolerated dose of R24 given as part of this combination was not reached. The toxicity of the regimen was moderate and included fever and urticaria, which were attributed to R24. Severe but reversible renal failure was noted in six patients in subsequent (two or more) treatment cycles, but when cisplatin was administered in 3% saline, this toxicity was not seen. Responses were seen in 2 of 19 patients receiving all three agents and in 1 of 4 patients