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Biologic and immune modulating agents in the treatment of childhood brain tumors
R J Packer1, E D Kramer, J A Ryan
1Department of Neurology, Children's National Medical Center, Washington, DC.
Abstract:
The data on the utility of biologic response modifiers are quite sketchy. Although no true home-runs have been hit, there is evidence that some patients will benefit from these immunologic agents. The majority of studies for central nervous system tumors have been done in adults with highly aggressive anaplastic gliomas. Many of these patients had extensive disease at the time of treatment and determination of benefit is difficult. Few pediatric trials have been attempted. The evidence for efficacy for most agents is lacking, although there are encouraging responses in children with isolated leptomeningeal spread to radiolabeled monoclonal antibodies and for patients with progressive intracranial mass lesions to one form of beta-interferon. Given the limited alternatives for many of these patients, and the neurotoxicity of other means of therapy, future studies are clearly indicated in children with malignant brain tumors. The lack of evidence of efficacy in adult glioblastoma trials cannot be used as direct evidence for the nonutility of these agents for childhood brain tumors. By and large, children tend to tolerate higher doses of biologic response modifiers than adults, again raising the hope of greater utility of these drugs for pediatric patients. From the information available, it seems unlikely that these immunomodulating agents, in themselves, will be effective in the treatment of the majority of patients with brain tumors. But in combination with aggressive surgery, radiation, and possibly chemotherapy, these agents may in time add to the armamentarium available for the treatment of childhood brain tumors.
Insights
Biologic response modifiers show limited efficacy alone for brain tumors. However, these immunologic agents may benefit some pediatric patients when combined with standard treatments.
Area of Science:
- Neuro-oncology
- Immunotherapy
Background:
- Limited data exists on the efficacy of biologic response modifiers (BRMs) for brain tumors.
- Most studies focus on adult anaplastic gliomas, with difficult benefit determination due to extensive disease.
- Pediatric trials are scarce, hindering understanding of BRM utility in children.
Purpose of the Study:
- To review the current evidence on the utility of biologic response modifiers in treating central nervous system tumors, particularly in pediatric populations.
- To assess the potential role of BRMs in pediatric brain tumor treatment given limited alternatives and treatment toxicities.
Main Methods:
- Review of existing literature on biologic response modifiers and their application in central nervous system tumors.
- Analysis of data from adult and pediatric clinical trials, focusing on efficacy and tolerability.
Main Results:
- Evidence for BRM efficacy is generally lacking, with some exceptions like radiolabeled monoclonal antibodies for leptomeningeal spread and beta-interferon for progressive lesions in children.
- Adult glioblastoma trials show limited efficacy, but this cannot be extrapolated to pediatric brain tumors.
- Children may tolerate higher doses of BRMs than adults, suggesting potential for greater utility.
Conclusions:
- BRMs are unlikely to be effective as monotherapy for most brain tumors.
- BRMs may offer future therapeutic benefits for childhood brain tumors when used in conjunction with surgery, radiation, and chemotherapy.
- Further studies are warranted to explore the role of BRMs in pediatric malignant brain tumors.