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Targeted immunotherapy for high-risk neuroblastoma--the role of monoclonal antibodies.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Parsons, Kerry Bernhardt, Brooke Strickland, Brandy
Spatial Coverage	United States
Description	Country affiliation: United States Author Affiliation: Parsons K ( Department of Pharmacy, Children's of Alabama, Birmingham, AL, USA. kerry.parsons@childrensal.org)
Abstract	OBJECTIVE: To systematically review clinical trials evaluating anti-disialoganglioside (GD2) antibodies in treating high-risk neuroblastoma in children. DATA SOURCES: A literature search was conducted in PubMed/MEDLINE, International Pharmaceutical Abstracts, and Cumulative Index of Nursing and Allied Health Literature (all searches 1990-August 2012) using the terms neuroblastoma, immunotherapy, 3F8, ch14.18, and hu14.18. Meeting abstracts presented between 1990 and 2012 from the American Society of Clinical Oncology, European Society for Medical Oncology, the American Society of Pediatric Hematology Oncology, Society of Surgical Oncology, and the American Society of Hematology were also evaluated. STUDY SELECTION AND DATA EXTRACTION: All completed and ongoing clinical trials of anti-GD2 antibodies in neuroblastoma were included. References from selected articles were also reviewed to identify additional citations. DATA SYNTHESIS: In 1999, the results of a Children's Cancer Group trial established that consolidation therapy after induction, surgery, and radiation should include purged autologous stem cell rescue followed by maintenance with isotretinoin. Overall survival at 7 years with this regimen remains below 30%. Over the following decade, antibodies targeting GD2, a surface antigen found on the surface of neuroblastoma cells, have emerged as a major therapeutic development for high-risk neuroblastoma. Anti-GD2 antibodies incite immune-mediated cytotoxicity toward neuroblastoma cells when given as monotherapy or in combination with cytokines such as sargramostim (granulocyte-macrophage colony-stimulating factor) or aldesleukin (interleukin-2). Responses to anti-GD2 agents appear most notable in patients with minimal residual disease following standard therapy. A chimeric preparation, ch14.18, is the only anti-GD2 antibody to be evaluated in a large controlled clinical trial, in which it demonstrated overall survival of 86% at 2 years in patients with high-risk neuroblastoma. Older nonrandomized studies of ch14.18 monotherapy and 3F8, a murine antibody, suggest this survival rate remains between 50 and 85% at 5 years posttreatment. CONCLUSIONS: Multiple GD2-specific monoclonal antibodies have been researched over the last decade in patients diagnosed with high-risk neuroblastoma. One anti-GD2 antibody, ch14.18, was found to significantly improve event-free and overall survival of high-risk neuroblastoma. Therefore, the standard approach to treating high-risk neuroblastoma is likely to undergo a major shift once an anti-GD2 antibody becomes commercially available.
File Format	HTM / HTML
ISSN	10600280
Issue Number	2
Volume Number	47
e-ISSN	15426270
Journal	Annals of Pharmacotherapy
Language	English
Publisher	SAGE Publications
Publisher Date	2013-02-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmaceutical Science Antibodies, Monoclonal Therapeutic Use Antineoplastic Agents Drugs, Investigational Gangliosides Antagonists & Inhibitors Neuroblastoma Drug Therapy Animals Administration & Dosage Adverse Effects Pharmacology Antibodies, Monoclonal, Humanized Antineoplastic Combined Chemotherapy Protocols Child Clinical Trials As Topic Metabolism Humans Risk United States Journal Article Review
Content Type	Text
Resource Type	Article
Subject	Pharmacology (medical)

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