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

With the use of cisplatin-based combination chemotherapy, metastatic testic ular germ-cell tumors can be cured in 70% to 80% of patients. The combinati on of cisplatin, etoposide and bleomycine (PEB) is considered standard ther apy, Patients refractory to cisplatin-based chemotherapy have a markedly po or prognosis. Several chemotherapeutic agents have been evaluated in intens ively pre-treated or cisplatin-refractory patients. Neither the anthracycli nes nor vinorelbine, topotecan or biological agents such as suramin and ret inoic acid have demonstrated clinical activity. Paclitaxel has been evaluat ed at different doses and schedules and yielded a response rate of 21% (ran ge 11-30%), with single patients achieving complete remissions. This has le d to the inclusion of paclitaxel in salvage regimens in combination with ci splatin and/or ifosfamide, Two studies have evaluated gemcitabine in refrac tory 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 a fter previous high-dose chemotherapy plus autologous stem-cell transplantat ion. The non-hematological toxicity of weekly gemcitabine at doses of 1,000 to 1,250 mg/m(2) was tolerable, and hematological side effects included th rombocytopenia in approximately 20% of patients. Ongoing studies in refract ory germ-cell tumors performed by the German Testicular Cancer Study Group are evaluating bendamustine, an alkylating agent with activity in breast an d small-cell lung cancer, and oxaliplatin, a platinum derivative with incom plete cross-resistance to cisplatin. Future trials combining new active age nts may examine alternating treatment strategies in patients with poor-prog nostic disease or as salvage treatment. (C) 1999 Wiley-Liss, Inc.