Phase I/II Study of a Cisplatin-Taxol-Dacarbazine Regimen in Metastatic Melanoma

OBJECTIVE: This phase I/II study was done to evaluate the safety and efficacy of a cisplatin-paclitaxel-dacarbazine regimen in patients with metastatic melanoma. PATIENTS AND METHODS: Chemotherapy-naive patients with surgically unresectable stage III/IV melanoma who had measurable lesions, no brain metastasis, and an Eastern Oncology Cooperative Group performance status of 0 or 1 were enrolled. Cohorts of 4 patients were treated at each dose level. The starting doses of the drugs were as follows: cisplatin 20 mg/m2 IV on days 1 to 4, paclitaxel 100 mg/m2 IV on days 1 and 8, and dacarbazine 800 mg/m2 IV on day 1 only. The doses of cisplatin and paclitaxel were escalated to the next dose level, until the maximum tolerable doses were reached. The dose level without dose-limiting grade 4 toxicity was chosen for phase II part of the study. The primary end point of the phase II study was to determine the antitumor activity in terms of response rate and survival of patients. RESULTS: The optimum chemotherapy doses for phase II study were as follows: cisplatin 20 mg/m2 on days 1 to 4, paclitaxel 120 mg/m2 on days 1 and 8, and dacarbazine 800 mg/m2 on day 1. Overall, 46 patients were enrolled in the study. Two complete and 17 partial responses were seen for an overall response rate of 41%. The median overall survival time and time to tumor progression were 11.0 and 4.3 months, respectively. Median response duration was 6.2 months. Myelosuppression and neuropathy were the dose-limiting toxicities. CONCLUSION: Cisplatin-paclitaxel-dacarbazine regimen is effective in patients with advanced melanoma.