RESUMEN
PURPOSE: The objective of this study was to further investigate the efficacy and safety of low-dose outpatient chemobiotherapy in patients with unresectable metastatic melanoma. PATIENTS AND METHODS: Thirty-one patients with histologically confirmed unresectable measurable metastatic melanoma were enrolled onto an open-label, multicenter phase II study. The treatment regimen consisted of oral temozolomide followed by subcutaneous biotherapy with granulocyte macrophage colony-stimulating factor, interferon-alfa, and recombinant interleukin-2 (rIL-2). RESULTS: Twenty-eight patients (90%) had M1c disease, and 58% had three or more sites of metastasis. Four patients (13%), all with M1c disease, had a complete response, and four patients had a partial response. The median progression-free survival was 4.9 months and the median overall survival was 13.1 months. Two patients (6%) developed CNS metastasis as the first site of disease progression, and 7 (23%) of 30 experienced CNS progression after receiving chemobiotherapy. A total of 112 cycles of therapy were administered. Toxicity occurred in 78% of the cycles and was grade 1 or 2 in the majority of cases and easily managed. Grade 4 toxicity occurred in 3% of the cycles. CONCLUSION: This low-dose chemobiotherapy combination produces clinical responses in patients with metastatic melanoma, even in those with M1c disease, is well tolerated, and allows home dosing. It offers a reasonable alternative to high-dose regimens, such as high-dose biochemotherapy or rIL-2 requiring prolonged periods of hospitalization, or single agent outpatient regimens, such as dacarbazine, which is usually not effective in patients with M1c disease. Furthermore, it may protect against the development of brain metastases.