Combination Chemotherapy Followed by Stem Cell Transplant in High-risk Neuroblastoma Patients

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)

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.