The antitumor activity of
zeniplatin, a third-generation, water-soluble
platinum compound that has shown broad preclinical antitumor activity and no significant nephrotoxicity in phase I trials, was tested in patients with advanced
malignant melanoma and advanced
renal cancer. Patients who had not previously been treated, except with local limb perfusion and
immunotherapy, were given
zeniplatin as bolus
injections at 125 mg/m2 every 3 weeks. The main hematological toxicity was
leukopenia (7/30 patients, WHO grade > or = 3) and the main nonhematological toxicity was
nausea and
vomiting (21/30 patients, WHO grade > or = 2). Serious nephrotoxicity was observed early in the
renal cancer study and, later, also in the
melanoma study.
Hyperhydration did not prevent the nephrotoxicity, and the studies were stopped after 6
renal cancer patients and 24
malignant melanoma 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 four patients were evaluable for response and none responded. The results show that
zeniplatin has some activity (14%) in patients with advanced
malignant melanoma, but no conclusion can be drawn regarding the activity of
zeniplatin in
renal cancer as the number of patients was too low. The main toxicities were
leukopenia and
nausea and
vomiting. Unexpected and serious nephrotoxicity was observed, and for this reason the studies were terminated before the planned number of patients had been included. A possible explanation for the nephrotoxicity may be drug interactions, but no firm conclusion can yet be drawn.