Phase I study of the combination of docetaxel, temozolomide and cisplatin in patients with metastatic melanoma

Purpose  In a search for more effective combination chemotherapy for the treatment of metastatic melanoma, we conducted a phase I trial of a novel combination of docetaxel, temozolomide, and cisplatin. Methods  Patients with inoperable or recurrent metastatic melanoma with a Zubrod performance status of 2 or less and adequate organ function were eligible. The dose of docetaxel was escalated between cohorts of patients, and the doses of temozolomide and cisplatin were fixed. A standard 3 + 3 dose escalation design was used to determine the maximum tolerated dose (MTD). Results  Among 23 patients who were enrolled, 21 were evaluable for toxicity. Eighteen patients (78%) had stage IV-M1c disease. The dose-limiting toxicities were myelosuppression and pulmonary embolism. The MTD was 30 mg/m² docetaxel on days 1, 8, and 15 when given with 150 mg/m² temozolomide on days 1–5, and 20 mg/m² cisplatin on days 1–4, repeating every 4 weeks. Among 19 patients evaluated for response, 6 (32%) had partial responses and 5 (26%) had stable disease. Among 14 chemo-naive patients, 6 (43%) had a partial response and 4 (29%) had stable disease. Nine patients developed brain metastases by the time of the last follow-up evaluation, and the median time to brain metastases for all 19 evaluable patients has not been reached. Conclusions  This combination was well tolerated and appears to be a promising treatment for patient with metastatic melanoma. This study was supported by Sanofi-Aventis.