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 resection and 2100 cGy hyperfractionated radiotherapy for local control, and for consolidation, targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m2).


METHODS
The chemotherapy consists of: cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2, for courses 1, 2, 4, and 6; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3, for courses 3, 5, and 7. 131I-3F8 is dosed at 20 mCi/kg, which is myeloablative and therefore necessitates stem-cell support.


RESULTS
Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis, 22 were stage 4 and two were unresectable stage 3 with MYCN amplification. Chemotherapy achieved CR/VGPR in 21 of 24 patients. Twenty patients to date have completed treatment with 131I-3F8, and 15 patients have completed all treatment. With a median follow-up of 19 months, 18 of 24 patients remain progression-free.


CONCLUSIONS
Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy, and self-limited pain and urticaria during antibody treatment. Late effects include hearing deficits and hypothyroidism.
Cheung
N K
NK
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. Cheungn@MSKCC.org
Kushner
B H
BH
LaQuaglia
M
M
Kramer
K
K
Gollamudi
S
S
Heller
G
G
Gerald
W
W
Yeh
S
S
Finn
R
R
Larson
S M
SM
Wuest
D
D
Byrnes
M
M
Dantis
E
E
Mora
J
J
Cheung
I Y
IY
Rosenfield
N
N
Abramson
S
S
O'Reilly
R J
RJ
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001855:Bone Marrow Diseases / Q000139:chemically induced; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology; D007116:Immunization, Passive; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D009363:Neoplasm Proteins / Q000097:blood; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D016499:Radioimmunotherapy / Q000009:adverse effects; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
C419226:3F8 antibody; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D018796:Immunoconjugates; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin