Phase II study of oxaliplatin, docetaxel, and sargramostim (GM-CSF) in patients with previously treated advanced melanoma

Abstract

8570 Background: Although much focus has been placed on immunotherapy for melanoma, further development of chemotherapy approaches is needed. Melanoma is responsive to platinum compounds and taxanes, but there is limited experience with combinations of these agents. Oxaliplatin has been reported to have detectable activity in melanoma, and a phase I study has identified a tolerable dose and schedule of oxaliplatin in combination with docetaxel and hematopoietic growth factor support. GM-CSF has a theoretical advantage of immune potentiation. These considerations supported study of oxaliplatin, docetaxel, and GM-CSF in patients with advanced melanoma. Methods: Eligibility included intact organ function, PS=2, at most one prior chemotherapy and one prior immunotherapy, no prior treatment with oxaliplatin or taxanes, and no chremophor allergy. After premedication, docetaxel was administered day 1 at 85 mg/m2, then oxaliplatin on day 2 at 85 mg/m2. GM-CSF (5 μg/kg) was administered s.c. days 3–12. Cycles were 21 days in length, and disease reevaluation was performed every 2 cycles by RECIST criteria. Results: 20 patients were enrolled, 13 with 1 prior therapy, 5 with 2 prior therapies, and 2 previously untreated. Six patients did not complete 2 cycles and were not formally evaluable for response. One patient who failed 2 prior treatment regimens experienced a minor response and received 10 cycles of therapy, and 4 patients had stable disease. The rest showed PD after 2 cycles. Notable toxicities included 7 cases of grade III/IV neutropenia and 2 hypersensitivity reactions. Conclusions: This combination of oxaliplatin, docetaxel, and GM-CSF has limited clinical activity in previously treated patients with advanced melanoma. Exploration in treatment-naive patients may still be warranted. No significant financial relationships to disclose.