Cisplatin, dacarbazine, and fotemustine plus interferon α in patients with advanced malignant melanoma: A multicenter phase II study of the Southern Italy Cooperative Oncology Group

BACKGROUND. In a previous study, the authors tested the combination of fotemustine (FM) 100 mg/m² intravenously (i.v.) on Day 1, dacarbazine (DTIC) 250 mg/m² i.v. on Days 2-5, and interferon α (IFNα) 3 MIU intramuscularly three times per week in 43 patients with advanced melanoma. An overall response rate of 40% and a median survival of 40 weeks were obtained. To evaluate whether the addition of cisplatin (CDDP) to this regimen could improve these results, the authors conducted a preliminary Phase I study and concluded that CDDP 25 mg/m² i.v. for 2 days can be combined safely with DTIC, FM, and IFNα. Herein, the authors report the results of a Phase II trial with this regimen. METHODS. From June 1996 to February 1999, 64 patients with metastatic melanoma who were not amenable to surgery were enrolled in this study. Sixty eligible patients (32 males and 28 females; median age, 53 years) were treated with a combination of FM 100 mg/m² i.v. on Day 1, DTIC 300 mg/m² i.v. on Days 2-4, and CDDP 25 mg/m² i.v. on Days 3 and 4 recycled every 3 weeks. IFN α2b was administered at a dose of 3 MIU intramuscularly 3 times per week until disease progression. RESULTS. A total of 189 courses were administered, with a median number of 3 courses per patient (range, 1-8 courses per patient). Eleven complete responses and 12 partial responses were observed, for an overall response rate of 38.3% (95% exact confidence interval, 26.1-51.8%). The median survival was 36 weeks. Neutropenia and thrombocytopenia affected 85% of patients and 68% patients and was World Health Organization Grade 3-4 in 40% and 50%, respectively. The side effects attributable to IFN α2b were mild and manageable. The other side effects were moderate and well controlled by supportive therapy. CONCLUSIONS. The schedule used in this study demonstrated significant activity in patients with advanced, untreated melanoma. The addition of CDDP in the management of the patients in this series seemed to increase significantly both the proportion of patients who achieved a complete response and the probability of long term survival compared with a previous series of patients who were treated by the authors. However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed.