Accelerated BEP for advanced germ cell tumors: An Australian multicenter phase I/II trial.

Abstract

4561 Background: Standard chemotherapy for advanced germ cell tumors is BEP (bleomycin, etoposide, cisplatin). 5-year survival is > 90% in good-risk disease, but only ~80% in intermediate and ~ 60% in poor risk disease. Accelerated (dose-dense) versions of standard regimens have proven more effective in other malignancies. We aimed to determine feasibility, tolerability and activity of an accelerated version of BEP. Methods: Single arm, multi-center, phase I/II trial (n=45 recruited). Target population was patients with advanced germ cell tumours and radiologically measurable disease. Patients with elevated serum tumour markers as only evidence of disease were ineligible. Treatment was cisplatin 20mg/m2 and etoposide 100mg/m2 on days 1-5, and pegylated G-CSF 6mg on day 6, all repeated every 2 weeks for 4 cycles (3 cycles for good risk). Bleomycin was given at 30kIU weekly to a total 12 doses (9 doses for good risk). Primary endpoint was regimen feasibility. Results: Results are presented for the 1st 41 patients enrolled from February 2008 to July 2010. 10 had poor risk disease (1 female), 15 intermediate risk, 16 good risk disease. Median follow-up is 14 months (range 2 to 27). At least 36 (88%) were eligible to start a 4th cycle of BEP on schedule or with no more than 1 week delay. Adverse events are presented in table 1. 22 of 41 patients (9 of 25 patients with intermediate or poor risk, 13 of 16 patients with good risk) achieved a complete response to chemotherapy +/- surgery. 4 of 41 patients have relapsed including one death. 1 year progression-free survival is 80% for intermediate or poor risk disease, and 100% for good risk disease. 1 year overall survival is 93% for intermediate or poor risk disease, and 100% for good risk disease. Conclusions: Feasibility and adverse events appears comparable to standard BEP. Efficacy data appears promising. Results from this trial and a similar study in the UK (Williams, ASCO 2008) provide the rationale for an international trial comparing accelerated versus standard versions of BEP. Number of patients with adverse events by CTCAE v3 criteria. G1/2 G3/4 Febrile neutropenia - 5 Other infection 7 6 Anemia 19 1 Nephrotoxicity 2 0 Neurotoxicity 19 0 Hearing loss 5 0 Tinnitus 30 0 Decrease in DLCO 38 0