Platinum-refractory germ cell tumors: an update on current treatment options and developments.

Abstract

In general, 50% up to 80% of metastasized germ cell tumor patients can be cured by platinum-based chemotherapy. However, 3-5% of patients will still die of platinum-refractory disease and new systemic treatment options are needed to improve treatment success in this difficult setting. This review aims to give an overview on treatment options and current developments in the field of platinum-refractory male germ cell tumors. A comprehensive literature search was conducted searching PubMed, Medline, Cochrane and Embase to identify clinical trials regarding the treatment of platinum-refractory disease. ASCO, EAU and ESMO conference proceedings were searched to identify unpublished results of relevant trials. Comprehensive review papers were hand searched for additional references. Clinicaltrials.gov was checked for ongoing clinical trials in the field of platinum-refractory germ cell tumors. Outcome of platinum-refractory disease remains poor. Single-agents with reasonable activity are gemcitabine, oxaliplatin and paclitaxel, but complete remissions resulting in long-term survival could not be achieved. The triple-combination of gemcitabine, oxaliplatin and paclitaxel followed by resection of residual masses provides the best outcomes with objective responses in 51% of patients and long-term survival in approximately 10-15%. To date, no molecularly targeted agent has shown reasonable activity. Treatment options for platinum-refractory disease are limited, but a small subset of patients may achieve long-term disease-free survival by multimodal treatment. The potential of novel targeted agents, i.e. by immune-checkpoint-inhibition remains to be defined.