A phase II study of aerosolized GM-CSF in the treatment of metastatic melanoma to the lung

Abstract

7571 Background: Metastatic malignant melanoma (MMM) remains a uniformly fatal condition. With the increasing incidence of melanoma worldwide, the need for active therapeutics is urgent. Herein we present the results of a phase II study utilizing aerosolized granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of MMM to the lung. Methods: A two-stage, multicenter, phase II clinical trial was conducted to assess the 2-month progression-free survival (PFS) rate, toxicity profile, and immuno-modulatory effects of aerosolized GM-CSF (250ug twice/day for 7 days of a 14-day treatment cycle) as treatment for MMM. Patients were at least 18 years old with histologically proven metastatic melanoma and radiographic evidence of active involvement of the lung. Results: Twenty-eight patients were accrued from 11/2000 through 9/2001. No patient was declared ineligible. Only one patient achieved a response (complete response) that lasted 12 months. The median PFS time among the 28 patients was 54 days with 8-week PFS rate of 43%. The median survival time was 223 days. Immunological studies comparing pre-treatment to post 4 weeks levels revealed little change in numbers of peripheral blood lymphocyte subsets. However, tetramer analysis of the frequency of melanoma differentiation-antigen peptide-specific cytotoxic T lymphocytes (CTL) in 3 of 4 patients studied, demonstrated evidence of increased CTL frequencies consistent with anti-tumor immunization. Conclusion: Although aerosolized GM-CSF therapy administered in the current regimen was able to demonstrate up-regulation of anti-melanoma T cell responses in 3 of 4 studied patients, beneficial clinical outcomes were not realized. In view of the low treatment-related toxicity and encouraging preliminary immunological evidence of increasing anti-melanoma T cell responses a further dose escalation study of aerosolized GM-CSF may prove more clinically/immunologically effective. No significant financial relationships to disclose.