Sequential high-dose chemotherapy protocol for relapsed poor prognosis germ cell tumors combining two mobilization and cytoreductive treatments followed by three high-dose chemotherapy regimens supported by autologous stem cell transplantation. Results of the phase II multicentric TAXIF trial

Background: High-dose chemotherapy (HD-CT) is able to circumvent platinum resistance of resistant/refractory germ-cell tumors (GCTs), but expectancy of cure remains low. New strategies are needed with new drugs and a sequential approach. Materials and methods: Patients with relapsed poor-prognosis GCTs were scheduled to receive two cycles combining epirubicin and paclitaxel (Taxol) followed by three consecutive HD-CT supported by stem cell transplantation [one course combining cyclophosphamide, 3 g/m2 + thiotepa, 400 mg/m2, followed by two ICE regimens (ifosfamide, 10 g/m2, carboplatin, AUC 20, etoposide, 1500 mg/m2)]. Results: From March 1998 to September 2001 (median follow-up, 31.8 months), 45 patients (median age, 28 years) were enrolled in this phase II study. Twenty-two patients received the complete course. Twenty-five patients died from progression and five from toxicity. The overall response rate was 37.7%, including an 8.9% complete response rate. The median overall survival was 11.8 months. The 3-year survival and progression-free survival rate was 23.5%. The ‘Beyer’ prognostic score predicted the outcome after HD-CT. Conclusion: Although our results warrant further studies on HD-CT in relapsed poor prognosis GCTs, patients with a Beyer score >2 did not benefit from this approach and should not be enrolled in HD-CT trials. Better selection criteria have to be fulfilled in forthcoming studies.