Reduction from seven to five cycles of intensive induction chemotherapy in children with high-risk neuroblastoma.
OBJECTIVE
We previously reported a high response rate with a dose-intensive chemotherapy regimen in 24 children with high-risk neuroblastoma (NB). We now describe similar results with changes that reduce toxicity (fewer cycles, less vincristine, use of granulocyte colony-stimulating factor).


METHODS
Eighty-seven consecutive newly diagnosed children with high-risk NB underwent induction that initially had seven cycles (57 patients) but was later limited to five (30 patients). Cycles 1, 2, 4, and 6 used cyclophosphamide (140 mg/kg)/doxorubicin (75 mg/m(2))/vincristine (0.15 mg/kg in the first 27 patients, 0.067 mg/kg subsequently). Cycles 3, 5, and 7 used cisplatin (200 mg/m(2))/etoposide (600 mg/m(2)). Tumor resection followed a minimum of three cycles. The induction was eventually modified to include anti-G(D2) immunotherapy after each of the last three cycles (38 patients).


RESULTS
Bone marrow disease resolved in 70 (91%) of 77 patients and was not detected pre- and postinduction in 10 patients. After cycle 3 or 4, 86% of primary tumors were more than 50% smaller. Postinduction metaiodobenzylguanidine scans showed normal radiotracer distribution in metastatic sites in 74 (87%) of 85 patients. Overall results were: 68 (79%) complete/very good partial responses (CR/VGPR); 14 (16%) partial responses (PR); three (3%) less than PR; one (1%) death from infection; and one patient not assessable for response. Five cycles yielded a CR/VGPR rate of 83%, compared with a 77% rate from seven cycles. Side effects were myelosuppression, mucositis, and hearing deficits; neurotoxicity was insignificant with the lower vincristine dosage. Four patients (each received seven cycles) developed myelodysplasia/leukemia.


CONCLUSIONS
Five cycles of this induction regimen, plus surgery, suffice to achieve CR/VGPR in approximately 80% of children with high-risk NB.
Kushner
Brian H
BH
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. kushnerb@mskcc.org
Kramer
Kim
K
LaQuaglia
Michael P
MP
Modak
Shakeel
S
Yataghene
Karima
K
Cheung
Nai-Kong V
NK
D000906:Antibodies / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005732:Gangliosides / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007167:Immunotherapy; D007223:Infant; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology*; D012307:Risk Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D000906:Antibodies; D005732:Gangliosides; D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; C019403:ganglioside, GD2; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin