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

• Published in: Annals of oncology Vol. 16; no. 3; pp. 411 - 418
• Main Authors: Lotz, J.-P., Bui, B., Gomez, F., Théodore, C., Caty, A., Fizazi, K., Gravis, G., Delva, R., Peny, J., Viens, P., Duclos, B., De Revel, T., Curé, H., Gligorov, J., Guillemaut, S., Ségura, C., Provent, S., Droz, J.-P., Culine, S., Biron, P.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-03-2005
• Subjects: Adolescent; Adult; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carboplatin - administration & dosage; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Epirubicin - administration & dosage; Etoposide - administration & dosage; germ-cell tumors; high-dose chemotherapy; Humans; Ifosfamide - administration & dosage; Infusions, Intravenous; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasms, Germ Cell and Embryonal - drug therapy; Neoplasms, Germ Cell and Embryonal - pathology; Paclitaxel - administration & dosage; Pharmacology. Drug treatments; Prognosis; Stem Cell Transplantation; Testicular Neoplasms - drug therapy; Testicular Neoplasms - pathology; Transplantation, Autologous; Treatment Outcome; Antineoplastic agent; germ-cell tumors; Relapse; Prognosis; Stem cell; Multicenter study; Hematopoietic cell; Germ cell tumor; Mobilization; Autograft; Chemotherapy; Treatment; Sequential; Clinical trial; High dose; high-dose chemotherapy
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdi087

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.