A phase II trial of high-dose chemotherapy (HDCT) supported by hematopoietic stem-cell transplantation (HSCT) in germ-cell tumors (GCTs) patients failing cisplatin-based chemotherapy: The multicentric TAXIF II study

F. Selle, S. Wittnebel, P. Biron, G. Gravis, G. Roubaud, B. N. Bui, R. Delva, J. O. Bay, A. Fléchon, L. Geoffrois, A. Caty, D. G. Soares, T. de Revel, K. Fizazi, J. Gligorov, J. M. Micléa, C. Dubot, S. Provent, I. Temby, M. GauletE. Horn, I. Brindel, J. P. Lotz

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    Abstract

    Background: High-dose chemotherapy (HDCT) is an effective salvage treatment of germ-cell tumors (GCTs) patients. In the first salvage setting, 30%-70% of patients may achieve durable remissions. Even when HDCT is administered assubsequent salvage treatment, up to 20% of patients may still be definitively cured. However, patients with refractory/relapsed disease still have a very poor long-term prognosis, requiring earlier intervention of HDCT. Patients and methods: This phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy. Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy, nonseminomatous GCT inrelapse after first or second lines, partial remission after first line, primary mediastinal GCT in first relapse. Patients receivedtwo cycles combining Epirubicin and Paclitaxel (Epi-Tax), followed by three consecutive HDCT, one using a Paclitaxel/Thiotepa (Thio-Tax) association and two using the 5-day Ifosfamide-Carboplatin-Etoposide regimen. The main objectivewas to determine the complete response rate.cycle, 39 two HDCT cycles, 29 could receive the whole protocol. Sixteen patients did not receive the entire protocol, including eight (17.7%) for toxic side-effects. Two patients (4.4%) died of toxicities, and 17 (37.7%) of disease progression. With a median follow-up time of 26 months (range, 4-51), the final overall response rate was 48.8% (including acomplete response rate of 15.5% and a partial response/negative serum markers rate of 26.6%) in an intent-to-treat analysis. The median progression-free survival (PFS) and overall survival (OS) times were 22 months [95% confidence interval(CI) 2-not reached] and 32 months (95% CI 4-49), respectively. The 2-year PFS was a plateau setup at 50% (95% CI 32-67) and the 2-year OS was 66% (95% CI 44-81).Conclusion: The TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatinbased chemotherapy. The toxic death rate remained acceptable in the field of HDCT regimens.

    Original languageEnglish
    Pages (from-to)1775-1782
    Number of pages8
    JournalAnnals of Oncology
    Volume25
    Issue number9
    DOIs
    Publication statusPublished - 1 Jan 2014

    Keywords

    • Germ-cell tumors
    • Hematopoietic stem-cell transplantation
    • High-dose chemotherapy
    • Nonrefractory patients
    • TAXIF II trial

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