Combination Chemotherapy Followed by Stem Cell Transplant in High-risk Neuroblastoma Patients (NB2004-HR)

Combination Chemotherapy Followed by Stem Cell Transplant and Isotretinoin in Treating Young Patients With High-risk Neuroblastoma

Improvement of event free survival of high-risk neuroblastoma patients by introduction of two additional topotecan containing chemotherapy cycles into the multimodal standard treatment (induction chemotherapy, myeloablative therapy, radiation, surgery as indicated, and consolidation therapy).

Experimental intervention (6 weeks + duration of the control intervention): 2 x N8 cycle (topotecan, cyclophosphamide, and etoposide) followed by standard arm treatment (i.e., control intervention) Control intervention (total duration 70-76 weeks): 3 x N5 cycle (cisplatin, etoposide, and vindesine) 3 x N6 cycle (vincristine, dacarbacine, ifosfamide, and doxorubicine), myeloablative chemotherapy with autologous stem cell transplantation (melphalan, carboplatin, etoposide) 9 x retinoic acid cycles (6 months, 3 months break, 3 months) supportive care (PCP/fungal prophylaxis, transfusions, antibiotics, G-CSF)

neuroblastoma, chemotherapy, autologous stem cell transplantation, radiotherapy, mIBG, tumor resection

Drug: Cycles N8, N5, and N6 Drug: topotecan, cyclophosphamide, and etoposide (N8 cycle) followed by Drug: cisplatin, etoposide, and vindesine (N5 cycle) and Drug: vincristine, dacarbacine, ifosfamide, and doxorubicine (N6 cycle) followed by myeloablative chemotherapy with autologous stem cell transplantation (melphalan, carboplatin, etoposide) and by 9 x retinoic acid cycles (6 months, 3 months break, 3 months)

Drug: Cycles N5 and N6 Drug: cisplatin, etoposide, and vindesine (N5 cycle) and Drug: vincristine, dacarbacine, ifosfamide, and doxorubicine (N6 cycle) followed by myeloablative chemotherapy with autologous stem cell transplantation (melphalan, carboplatin, etoposide) and by 9 x retinoic acid cycles (6 months, 3 months break, 3 months)

Standard arm six chemotherapy cycles (3xN5 and 3x N6) followed by myeloablative therapy with stem cell support and isotretinoin

Inclusion Criteria: neuroblastoma stage 4 neuroblastoma and age ≥1 - 21 years or MYCN amplification and age ≥6 months - 21 years informed consent obtained Exclusion Criteria: Participation in other trials Pregnancy, lactation, or insufficient contraception for girls in childbearing age, Any concomitant non-protocol anticancer therapy, Incomplete initial staging.

Berthold F, Hero B, Kremens B, Handgretinger R, Henze G, Schilling FH, Schrappe M, Simon T, Spix C. Long-term results and risk profiles of patients in five consecutive trials (1979-1997) with stage 4 neuroblastoma over 1 year of age. Cancer Lett. 2003 Jul 18;197(1-2):11-7. doi: 10.1016/s0304-3835(03)00076-4.

Berthold F, Boos J, Burdach S, Erttmann R, Henze G, Hermann J, Klingebiel T, Kremens B, Schilling FH, Schrappe M, Simon T, Hero B. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol. 2005 Sep;6(9):649-58. doi: 10.1016/S1470-2045(05)70291-6.

Langler A, Christaras A, Abshagen K, Krauth K, Hero B, Berthold F. Topotecan in the treatment of refractory neuroblastoma and other malignant tumors in childhood - a phase-II-study. Klin Padiatr. 2002 Jul-Aug;214(4):153-6. doi: 10.1055/s-2002-33175.

Berthold F, Hero B. Neuroblastoma: current drug therapy recommendations as part of the total treatment approach. Drugs. 2000 Jun;59(6):1261-77. doi: 10.2165/00003495-200059060-00006.