Highly effective induction therapy for stage 4 neuroblastoma in children over 1 year of age Journal Article


Authors: Kushner, B. H.; LaQuaglia, M. P.; Bonilla, M. A.; Lindsley, K.; Rosenfield, N.; Yeh, S.; Eddy, J.; Gerald, W. L.; Heller, G.; Cheung, N. K. V.
Article Title: Highly effective induction therapy for stage 4 neuroblastoma in children over 1 year of age
Abstract: Purpose: To test the efficacy of a protocol for poor-risk neuroblastoma that builds on the following: (1) our favorable previously reported results with dose-intensive use of cyclophosphamide; (2) our retrospective analysis of neuroblastoma chemotherapy reports, which supported the value of high- dose cisplatin and etoposide (VP-16); and (3) the Goldie-Coldman hypothesis that rapid cytoreduction plus the use of non-cross-resistant chemotherapy combinations will decrease the risk of drug resistance. Patients and Methods: The N6 protocol included seven courses of high-dose chemotherapy plus surgical resection of bulk disease. Courses 1, 2, 4, and 6 consisted of 6- hour intravenous infusions of cyclophosphamide 70 mg/kg/d on days 1 and 2 (ie, 140 mg/kg per course), a 72-hour intravenous infusion of doxorubicin 75 mg/m2 and vincristine 0.1 mg/kg beginning day 1, and vincristine 1.5 mg/m2 intravenous bolus on day 9. Courses 3, 5, and 7 consisted of 2-hour intravenous infusions of VP-16 200 mg/m2/d on days 1 to 3 (ie, 600 mg/m2 per course), and 1-hour intravenous infusions of cisplatin 50 mg/m2/d on days 1 to 4 (ie, 200 mg/m2 per course). Courses were to start after neutrophil counts reached 500/μL and platelet counts reached 100,000/μL. Response was defined by international criteria. Results: Among 24 consecutive previously untreated patients diagnosed with stage 4 neuroblastoma at more than 1 year of age, 21 patients achieved a complete or very good partial remission; one patient had no evidence of disease except by iodine-131- metaiodobenzylguanidine (MIBG) scan, which was markedly improved; and one patient had resolution of extensive metastatic disease, but still had an incompletely resected primary tumor. The sole patient to have a poor response had clinical features at diagnosis that are atypical for neuroblastoma, namely, 8 years of age and an unknown primary tumor. Severe toxicities included myelosuppression, mucositis, and hearing deficits. Conclusion: The N6 approach reliably achieves significant cytoreduction against stage 4 neuroblastoma. This may eventuate in an improved cure rate, since consolidative treatments using myeloablative therapy, immunotherapy, or biologic response modifiers such as cis-retinoic acid are most likely to be effective against minimal residual disease.
Keywords: child; clinical article; cisplatin; doxorubicin; dose response; drug efficacy; cancer staging; drug megadose; bone marrow suppression; etoposide; mucosa inflammation; cyclophosphamide; vincristine; drug resistance; infant; neuroblastoma; patient compliance; thrombocyte count; reliability; (3 iodobenzyl)guanidine i 131; hearing impairment; lymphocyte count; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 12
Issue: 12
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 1994-12-01
Start Page: 2607
End Page: 2613
Language: English
DOI: 10.1200/jco.1994.12.12.2607
PROVIDER: scopus
PUBMED: 7527454
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Samuel D J Yeh
    82 Yeh
  2. Brian Kushner
    232 Kushner
  3. Glenn Heller
    354 Heller
  4. Nai-Kong Cheung
    532 Cheung
  5. Nancy S Rosen
    27 Rosen
  6. William L Gerald
    375 Gerald
  7. Mary Ann Bonilla
    20 Bonilla