A phase II study of bortezomib in the treatment of metastatic malignant melanoma

BACKGROUND: Bortezomib is a proteasome inhibitor with manageable clinical toxicity and laboratory evidence of anti-melanoma activity. Therefore, it was considered for clinical testing in patients with metastatic melanoma. METHODS: Patients with metastatic melanoma and adequate hematologic, renal, and hepatic function were treated with bortezomib (a 1.5-mg/m2 intravenous bolus twice weekly for 2 of every 3 weeks). Eligible patients were age > or = 18 years with an Eastern Cooperative Oncology Group performance status of 0-1. The primary goal of the current study was to evaluate the 18-week disease progression-free survival rate and tolerability of bortezomib in these patients. RESULTS: The current study was intended to treat 45 patients. It was closed at the planned interim analysis due to early evidence of insufficient clinical efficacy. Twenty-seven patients with a median age of 56 years (range, 32-77 years)were accrued. There were no major clinical responses to treatment. Only 6 patients (22%) achieved stable disease. Of these 6 patients, 4 were still stable after 4 cycles of treatment, but were removed from the study due to toxicity. The median time to disease progression was 1.5 months (95% confidence interval [95% CI], 1.4-1.6) with a median overall survival of 14.5 months (95% CI, 9-22). Having failed bortezomib, most patients proceeded to other clinical trials. Twenty-six patients were evaluable for toxicity. One patient was removed from the study for other reasons and could not return for the cycle evaluation and thus was never evaluated. Of the 26 patients, no Grade 4/5 treatment-related toxicities (using the National Cancer Institute Common Toxicity Criteria [version 2.0]) were reported. Eleven patients (42%) had Grade 3 toxicities (believed to be at least possibly related to treatment), including sensory neuropathy, thrombocytopenia, constipation, fatigue, ileus, abdominal pain, and infection without neutropenia. The median number of treatment cycles patients received was two (range, one to six treatment cycles). Two patients (7%) had 1 dose delay and 6 patients (22%) had dose reductions during 1 treatment cycle due to adverse events. CONCLUSIONS: Single-agent bortezomib, administered twice weekly x 2 weeks, every 3 weeks at a dose of 1.5 mg/m2, was not found to be effective in the treatment of patients with metastatic melanoma.