Reduction from seven to five cycles of intensive induction chemotherapy in children with high-risk neuroblastoma Journal Article

Authors: Kushner, B. H.; Kramer, K.; LaQuaglia, M. P.; Modak, S.; Yataghene, K.; Cheung, N. K. V.
Article Title: Reduction from seven to five cycles of intensive induction chemotherapy in children with high-risk neuroblastoma
Abstract: Purpose: 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). Patients and 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/m2)/vincristine (0.15 mg/kg in the first 27 patients, 0.067 mg/kg subsequently). Cycles 3, 5, and 7 used cisplatin (200 mg/m2)/etoposide (600 mg/m2). Tumor resection followed a minimum of three cycles. The induction was eventually modified to include anti-GD2 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. Conclusion: Five cycles of this induction regimen, plus surgery, suffice to achieve CR/VGPR in ≈80% of children with high-risk NB.
Keywords: cancer chemotherapy; child; controlled study; preschool child; treatment outcome; treatment response; child, preschool; leukemia; cancer surgery; unclassified drug; major clinical study; clinical trial; cisplatin; doxorubicin; dose response; neurotoxicity; antineoplastic agent; cancer immunotherapy; multiple cycle treatment; bone marrow suppression; etoposide; mucosa inflammation; antineoplastic combined chemotherapy protocols; risk factors; combination chemotherapy; cyclophosphamide; vincristine; pathology; dose-response relationship, drug; risk factor; high risk patient; monoclonal antibody; cause of death; immunology; immunotherapy; drug distribution; infant; neuroblastoma; (3 iodobenzyl)guanidine; antibodies; granulocyte colony stimulating factor; granulocyte colony-stimulating factor; hearing disorder; antibody; bone marrow disease; gangliosides; ganglioside; ganglioside, gd2; myelodysplasia; monoclonal antibody gd2; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 22
Issue: 24
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2004-12-15
Start Page: 4888
End Page: 4892
Language: English
DOI: 10.1200/jco.2004.02.101
PROVIDER: scopus
PUBMED: 15611504
Notes: J. Clin. Oncol. -- Cited By (since 1996):43 -- Export Date: 16 June 2014 -- CODEN: JCOND -- Source: Scopus
Altmetric Score
MSK Authors
  1. Brian Kushner
    192 Kushner
  2. Nai-Kong Cheung
    447 Cheung
  3. Kim Kramer
    170 Kramer
  4. Shakeel Modak
    160 Modak