Paclitaxel-based chemotherapy for patients with refractory or relapsed nonseminomatous germ cell tumors

Germ cell tumors have been the paradigm for successful solid tumor therapy. With multimodality treatment including surgery and/or chemotherapy and/or radiation therapy 75% of all patients with germ cell tumors will be cured o f their malignancy. However, in patients who have primary refractory or rel apsed disease, the cure rate is less than 20%. Treatment strategies in this patient population have included: (1) dose intense therapies such as alter nating sequential chemotherapy with multiple active regimens given in short intervals, (2) dose dense therapy with high-dose chemotherapy and stem cel l support, (3) new agents, and (4) salvage surgery, prognostic stratificati on of patients in a salvage setting can help to determine which therapeutic modalities may provide the greatest opportunity for success. The evaluatio n of new agents has historically occurred in the salvage setting followed b y the development of combinations and then advancement to nonsalvage therap y. The introduction of paclitaxel, with its novel mechanism of action and p reclinical activity, resulted in its evaluation as a single agent in patien ts with refractory or relapsed nonseminomatous germ cell tumors. As a singl e agent, paclitaxel has an overall response rate of 13.3% in a heavily pret reated salvage population. The preclinical evaluation of the combination of paclitaxel and cisplatin allowed for the most appropriate sequencing and d osing of the two agents. In addition, preclinical evaluation suggests that these agents are synergistic as well as active in cisplatin-refractory dise ase. The combination of paclitaxel and cisplatin was evaluated clinically a nd demonstrated an overall response rate of 30%. Doxorubicin is an active a gent in germ cell tumors and has nonoverlapping toxicity with pactitaxel an d cisplatin. The majority of patients treated in a community setting have n ot had prior exposure to this agent. Therefore, the regime of doxorubicin, paclitaxel, and cisplatin (ATP) was developed and in a small number of pati ents was utilized in the salvage setting with a 25% response rate. A pilot study with ATP therapy for patients with nonseminomatous germ cell tumors w ho have disease progression during induction therapy or first and second sa lvage regimens and who have received a total of more than six courses of pr ior chemotherapy is ongoing. (C) 2000 Elsevier Science Inc. All rights rese rved.