Phase II clinical trial of oxaliplatin and bevacizumab in refractory metastatic germ cell tumors (GCT).

Abstract

4579 Background: Salvage chemotherapy with Ifosfamide based regimen or high dose chemotherapy (HDCT) has curative potential in GCTs. We still need novel therapies for patients where cure is not possible. Oxaliplatin has single agent activity in refractory GCTs. Bevacizumab in combination with chemotherapy has activity in many solid tumors but has not been studied in GCTs. This is the first study of bevacizumab in refractory GCT patients. Methods: Patients with serologically or histologically proven metastatic GCT who have failed cisplatin based combination chemotherapy and progressed on salvage therapy were eligible. Prior HDCT and paclitaxel plus gemcitabine were required unless late relapse or primary mediastinal non-seminomatous GCT (NSGCT). Oxaliplatin was given 85 mg/m2 and bevacizumab 10 mg/kg every 2 weeks with a maximum of 14 cycles. Results: 25 total patients have been enrolled with 24 evaluable and 1 too early to evaluate. 9 were late relapses and 5 with primary mediastinal NSGCT. Median number of previous chemotherapies was 4 including 13 with prior HDCT. Median number of cycles administered was 5. There were 7 (29%) objective responders. Median duration of response was 6 months (range 4 to 22 months). Of these 7 patients 3 had normalization of HCG and/or AFP. One additional patient had serologic response (>1 log reduction in HCG) for 5 months with stable radiographic lesions. Median survival was 8 months (range 2 to 40 months). Four patients had Grade 3 adverse events (peripheral neuropathy, hypertension, seizures and DVT). Conclusions: Oxaliplatin plus bevacizumab has promising activity in heavily pretreated GCTs with manageable toxicity.