Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen versus dacarbazine alone in advanced melanoma patients

This randomized phase II trial was performed to define the activity and tox icity of the combination of dacarbazine (DTIC), carmustine (BCNU), cisplati n (DDP) and tamoxifen (DBDT regimen) versus DTIC alone in patients with met astatic melanoma. Sixty patients with metastatic melanoma were randomly ass igned to receive BCNU 150 mg/m(2) intravenously (i.v.) on day 1, cisplatin 25 mg/m(2) i.v. daily on days 1 to 3, DTIC 220 mg/m(2) i.v. daily on days 1 to 3 and tamoxifen 160 mg orally daily for 7 days prior to chemotherapy (D BDT arm; arm A). Treatment cycles were repeated every 28 days, while BCNU w as given every two cycles. The DTIC arm (arm B) patients received DTIC alon e 1200 mg/m(2) i.v. on day 1, repeated every 21 days. Patients were evaluat ed every two cycles; responding patients continued the treatment for a maxi mum of 12 cycles. The overall response rate was 26% in the DBDT arm and 5% in the DTIC arm. Complete responses were 2.5% for DBDT and 0% for DTIC. The median progression-free survival and the median survival were 4 and 9 mont hs, respectively for DBDT, and 2 and 7 months for DTIC, DBDT was associated with significant haematological toxicity: 33% of the patients experienced a grade III or IV neutropenia and 28% a grade III or IV thrombocytopenia. I n conclusion, the overall response rate obtained with DBDT was greater than that obtained with DTIC alone; however, this combination increases toxicit y with limited impact on overall survival. 2001 Lippincott Williams & Wilki ns.