N7: A novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age

Background. The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy (as in N6 protocol [Kushner et al.:J Clin Oncol 12:2607-2613, 1994] but with lower dosing of vincristine) for induction, surgical resect ion and 2100 cGy hyperfractionated radiotherapy for local control, and for consolidation, targeted radioimmunotherapy with I-131-labeled anti-G(D2) 3F 8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m(2)). Procedure. The chemotherapy consists of: cyclophosphamide 70 mg/k g/d x2 and a 72-hr infusion of doxorubicin 75 mg/m(2) plus vincristine 2 mg /m(2), for courses 1, 2, 4, and 6; and cisplatin 50 mg/m(2)/d x4 and etopos ide 200 mg/m(2)/d x 3, for courses 3, 5, and 7. I-131-3F8 is dosed at 20 mC i/kg, which is myeloablative and therefore necessitates stem-cell support. Results. Of the first 24 consecutive previously untreated patients more tha n 1 year old at diagnosis, 22 were stage 4 and two were unresectable stage 3 with MYCN amplification. Chemotherapy achieved CRr/VGPR in 21 of 24 patie nts. Twenty patients to date have completed treatment with I-131-3F8, and 1 5 patients have completed all treatment. With a median follow-up of 19 mont hs, 18 of 24 patients remain progression-free. Conclusions. Major toxicitie s were grade 4 myelosuppression and mucositis during chemotherapy, and self -limited pain and urticaria during antibody treatment. Late effects include hearing deficits and hypothyroidism. Med. Pediatr. Oncol. 36:227-230, 2001 . (C) 2001 Wiley-Liss, Inc.