Treatment of patients with cisplatin-refractory testicular germ-cell cancer

Abstract

With the use of cisplatin-based combination chemotherapy, metastatic testicular germ-cell tumors can be cured in 70% to 80% of patients. The combination of cisplatin, etoposide and bleomycine (PEB) is considered standard therapy. Patients refractory to cisplatin-based chemotherapy have a markedly poor prognosis. Several chemotherapeutic agents have been evaluated in intensively pre-treated or cisplatin-refractory patients. Neither the anthracyclines nor vinorelbine, topotecan or biological agents such as suramin and retinoic acid have demonstrated clinical activity. Paclitaxel has been evaluated at different doses and schedules and yielded a response rate of 21% (range 11-30%), with single patients achieving complete remissions. This has led to the inclusion of paclitaxel in salvage regimens in combination with cisplatin and/or ifosfamide. Two studies have evaluated gemcitabine in refractory germ-cell tumors and demonstrated a response rate of 17% (95% CI 7-28%) in 52 intensively pre-treated patients, two-thirds of whom had relapsed after previous high-dose chemotherapy plus autologous stem-cell transplantation. The non-hematological toxicity of weekly gemcitabine at doses of 1,000 to 1,250 mg/m2 was tolerable, and hematological side effects included thrombocytopenia in approximately 20% of patients. Ongoing studies in refractory germ-cell tumors performed by the German Testicular Cancer Study Group are evaluating bendamustine, an alkylating agent with activity in breast and small-cell lung cancer, and oxaliplatin, a platinum derivative with incomplete cross-resistance to cisplatin. Future trials combining new active agents may examine alternating treatment strategies in patients with poor-prognostic disease or as salvage treatment.