A phase II study of oxaliplatin, docetaxel, and GM-CSF in patients with previously treated advanced melanoma.

PURPOSE: 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 the study of oxaliplatin, docetaxel, and GM-CSF in patients with advanced melanoma.
METHODS: Eligibility included adequate organ function, PS<or=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 75 mg/m2, then oxaliplatin on day 2 at 85 mg/m2. GM-CSF (250 mcg/m2) was administered s.c. days 3-12. Cycles were 21 days in length, and disease reevaluation was performed every two cycles by RECIST criteria.
RESULTS: Nineteen patients received at least one cycle, eight with one prior systemic therapy, five with two prior systemic therapies. Five patients did not complete two cycles and were not formally evaluable for response. Five patients had stable disease (SD), including one who failed two prior therapies and went on to receive ten cycles. The remaining nine patients displayed progressive disease (PD) after two cycles. Notable toxicities included seven cases (37%) of grade III/IV neutropenia and two (11%) 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-naïve patients may still be warranted.