ZENIPLATIN IN ADVANCED MALIGNANT-MELANOMA AND RENAL-CANCER - PHASE-IISTUDIES WITH UNEXPECTED NEPHROTOXICITY

The antitumor activity of zeniplatin, a third-generation, water-solubl e platinum compound that has shown broad preclinical antitumor activit y and no significant nephrotoxicity in phase I trials, was tested in p atients with advanced malignant melanoma and advanced renal cancer. Pa tients who had not previously been treated, except with local limb per fusion and immunotherapy, were given zeniplatin as bolus injections at 125 mg/m(2) every 3 weeks. The main hematological toxicity was leukop enia (7/30 patients, WHO grade greater than or equal to 3) and the mai n nonhematological toxicity was nausea and vomiting (21/30 patients, W HO grade greater than or equal to 2). Serious nephrotoxicity was obser ved early in the renal cancer study and, later, also in the melanoma s tudy. Hyperhydration did not prevent the nephrotoxicity, and the studi es were stopped after 6 renal cancer patients and 24 malignant melanom a patients had been included. Zeniplatin gave objective responses in 3 of the 21 evaluable malignant melanoma patients [2 complete responses (CRs) in patients with lymph-node metastases lasted 5 and 14 months, respectively; 1 partial response (PR) in a patient with lymph-node and liver metastases lasted 6 months]. In the renal cancer study, only fo ur patients were evaluable for response and none responded. The result s show that zeniplatin has some activity (14%) in patients with advanc ed malignant melanoma, but no conclusion can be drawn regarding the ac tivity of zeniplatin in renal cancer as the number of patients was too low. The main toxicities were leukopenia and nausea and vomiting. Une xpected and serious nephrotoxicity was observed, and for this reason t he studies were terminated before the planned number of patients had b een included. A possible explanation for the nephrotoxicity may be dru g interactions, but no firm conclusion can yet be drawn.