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Current and Future Strategies for Relapsed Neuroblastoma: Challenges on the Road to Precision Therapy

Morgenstern, Daniel A. MD, PhD; Baruchel, Sylvain MD; Irwin, Meredith S. MD

Journal of Pediatric Hematology/Oncology:
doi: 10.1097/MPH.0b013e318299d637
Invited Review Article
Abstract

More than half of the patients with high-risk neuroblastoma (NB) will relapse despite intensive multimodal therapy, with an additional 10% to 20% refractory to induction chemotherapy. Management of these patients is challenging, given disease heterogeneity, resistance, and organ toxicity including poor hematological reserve. This review will discuss the current treatment options and consider novel therapies on the horizon. Cytotoxic chemotherapy regimens for relapse and refractory NB typically center on the use of the camptothecins, topotecan and irinotecan, in combination with agents such as cyclophosphamide and temozolomide, with objective responses but poor long-term survival. 131I-meta-iodobenzylguanidine therapy is also effective for relapsed patients with meta-iodobenzylguanidine-avid disease, with objective responses in a third of cases. Immunotherapy with anti-GD2 has recently been incorporated into upfront therapy, but its role in the relapse setting remains uncertain, especially for patients with bulky disease. Future cell-based immunotherapies and other approaches may be able to overcome this limitation. Finally, many novel molecularly targeted agents are in development, some of which show specific promise for NB. Successful incorporation of these agents will require combinations with conventional cytotoxic chemotherapies, as well as the development of predictive biomarkers, to ultimately personalize approaches to patients with “targetable” molecular abnormalities.

Author Information

Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada

D.A.M. is a Sears Foundation/Garron Family Cancer Centre Fellow part funded by the Hospital for Sick Children Restracomp. M.S.I. is supported by the Canadian Cancer Society Research Institute and a Canada Research Chair in Cancer Biology. The other author declares no conflict of interest.

Reprints: Meredith S. Irwin, MD, Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8 (e-mail: meredith.irwin@sickkids.ca).

Received April 8, 2013

Accepted May 1, 2013

© 2013 by Lippincott Williams & Wilkins.