Pilot study of high-dose, concurrent biochemotherapy for advanced melanoma

BACKGROUND. Durable complete response rates ranging from 5% to 20% have been reported in association with biochemotherapy for patients with metastatic melanoma, with response rates on the low end of this range being observed in trials that used lower doses and less intense treatment schedules. In the current study, the authors addressed the feasibility of increasing the doses of agents used in concurrent biochemotherapy. METHODS. Three patients with metastatic melanoma were enrolled at each of six concurrent biochemotherapy dose levels. The doses were as follows: dacarbazine 800 mg/m(2) or 1000 mg/m(2) (Day 1); cisplatin 25 mg/m(2) or 30 mg/m(2) (Days 1-4); vinblastine 1.6 mg/m(2) or 1.8 mg/m(2) (Days 1-5); interleukin-2 9 million units (MU) per m(2) or 12 MU/m(2) as a 24-hour continuous infusion (Days 1-4); and interferon-alpha-2b 5 MU/m(2), 10 MU/m(2), or 15 MU/m(2) (Days 1-5) and 5 MU/m(2) (Days 7, 9, and 11) administered subcutaneously. RESULTS. Of the 19 patients who were enrolled, 18 were evaluable for toxicity and response. Sixty-nine treatment courses were administered in total (median, 4 courses per patient; range, 1-6 courses per patient), with reduction of the dose of at least 1 agent being required in 7 courses (10%). Twenty-six courses were delayed by a median of 7 days (range, 3-29 days), with interferon-alpha-2b administration frequently omitted because of thrombocytopenia, most often after Day 5. Blood product support was required in 40 courses. Dose-limiting toxic effects included global encephalopathy, renal and hepatic dysfunction, pancreatitis, and ileus. There was 1 complete response, and there were 10 partial responses. The median time to disease progression was 6.9 months, and the median survival duration was 12.2 months. CONCLUSIONS. Although dose intensification can be achieved safely in patients with advanced melanoma, other strategies should be pursued to enhance the clinical activity of biochemotherapy as a response induction regimen. (C) 2004 American Cancer Society.