Pediatric Ependymoma Medication

  • Author: Tobey MacDonald, MD; Chief Editor: Max J Coppes, MD, PhD, MBA   more...
 
Updated: Feb 29, 2012
 

Medication Summary

The role of chemotherapy in the treatment of ependymoma has not been established.

Numerous drugs have been identified with activity against ependymoma in single-agent chemotherapy regimens in phase II trials. Of these, platinum compounds have been the most active (eg, cisplatin is the most effective single agent, with a 30% response rate).

Despite these findings, combination chemotherapeutic regimens for ependymoma have yielded disappointing results. The most encouraging data have been reported in infants using postoperative therapy consisting of cisplatin, cyclophosphamide, etoposide, and vincristine, with deferred radiation (2-y survival rate of 74%).

Current trials are evaluating the benefits of this regimen in older children with postoperative residual disease. At present, no definitive conclusions can be drawn.

An example of the dosing and administration of preirradiation chemotherapeutic agents used in a recent investigational protocol for children older than 3 years with postoperative residual disease is provided below.[3]

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Antineoplastic agents

Class Summary

These agents disrupt DNA replication, which inhibits tumor growth and promotes tumor cell death. Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. After cells divide, they enter a period of growth (phase G1), followed by DNA synthesis (phase S). The next phase is a premitotic phase (G2), then finally a mitotic cell division (phase M).

The cell division rate varies for different tumors. Most common cancers increase very slowly in size compared to normal tissues, and the rate may decrease further in large tumors. This difference allows normal cells to recover more quickly than malignant ones from chemotherapy and is the rationale behind current cyclic dosage schedules.

Antineoplastic agents interfere with cell reproduction. Some agents are cell cycle specific, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not phase-specific. Cellular apoptosis (ie, programmed cell death) is also a potential mechanism of many antineoplastic agents.

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Vincristine (Oncovin)

 

Plant-derived vinca alkaloid. Acts as a mitotic inhibitor by binding tubulin. Inhibits microtubule formation in the mitotic spindle, causing metaphase arrest.

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Cisplatin (Platinol)

 

Heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation. This leads to interstrand and intrastrand DNA crosslinks and inhibition of DNA replication.

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Cyclophosphamide (Cytoxan)

 

Exerts its cytotoxic effect by alkylation of DNA, leading to interstrand and intrastrand DNA crosslinks, DNA-protein crosslinks, and inhibition of DNA replication.

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Etoposide (VePesid, VP-16)

 

Glycosidic derivative of podophyllotoxin that exerts its cytotoxic effect through stabilization of the normally transient covalent intermediates formed between DNA substrate and topoisomerase II, leading to single-stand and double-strand DNA breaks.

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Antidote, cyclophosphamide-induced hemorrhagic cystitis

Class Summary

This agent is a detoxifying agent used as a protectant against hemorrhagic cystitis induced by cyclophosphamide.

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Mesna (Mesnex)

 

In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity. Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity.

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Colony-stimulating factors

Class Summary

These agents reduce the duration of neutropenia and the associated risk of infection in patients receiving myelosuppressive chemotherapy. They act as a hematopoietic growth factor that stimulates the development of granulocytes. They are used to treat or prevent neutropenia when receiving myelosuppressive cancer chemotherapy and to reduce the period of neutropenia associated with bone marrow transplantation. These agents are also used to mobilize autologous peripheral blood progenitor cells for bone marrow transplantation and in the management of chronic neutropenia.

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Filgrastim (Neupogen, G-CSF)

 

Granulocyte colony-stimulating factor that activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils.

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Contributor Information and Disclosures
Author

Tobey MacDonald, MD  Clinical Director of Neuro-Oncology, Children's Hospital National Medical Center; Associate Professor, Department of Pediatric Hematology-Oncology, George Washington University

Tobey MacDonald, MD is a member of the following medical societies: American Association for Cancer Research, Children's Oncology Group, Pediatric Brain Tumor Consortium, and Society for Neuro-Oncology

Disclosure: Nothing to disclose.

Coauthor(s)

Roger J Packer, MD  Senior Vice President, Neuroscience and Behavioral Medicine, Director, Brain Tumor Institute, Children's National Medical CenterProfessor of Neurology and Pediatrics, The George Washington University

Roger J Packer, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Pediatric Society, Child Neurology Society, Children's Oncology Group, Neurofibromatosis Clinical Trials Consortium, Pediatric Brain Tumor Consortium, and Society for Neuro-Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Samuel Gross, MD  Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University

Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Timothy P Cripe, MD, PhD  Professor of Pediatrics, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center; Clinical Director, Musculoskeletal Tumor Program, Co-Medical Director, Office for Clinical and Translational Research, Cincinnati Children's Hospital Medical Center; Director of Pilot and Collaborative Clinical and Translational Studies Core, Center for Clinical and Translational Science and Training, University of Cincinnati College of Medicine

Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville School of Medicine

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA  Senior Vice President, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

References

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  2. Sung KW, Lim DH, Lee SH, Yoo KH, Koo HH, Kim JH, et al. Tandem high-dose chemotherapy and autologous stem cell transplantation for anaplastic ependymoma in children younger than 3 years of age. J Neurooncol. Nov 12 2011;[Medline].

  3. Bouffet E, Hawkins CE, Balloura W, Taylor MD, Bartels UK, Schoenhoff N, et al. Survival Benefit for Pediatric Patients with Recurrent Ependymoma Treated with Reirradiation. Int J Radiat Oncol Biol Phys. Jan 13 2012;[Medline].

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  7. Goldwein JW, Glauser TA, Packer RJ. Recurrent intracranial ependymomas in children. Survival, patterns of failure, and prognostic factors. - Packer RJ. Aug 1 1990;66(3):557-63. [Medline].

  8. Grundy RG, Wilne SA, Weston CL, et al. Primary postoperative chemotherapy without radiotherapy for intracranial ependymoma in children: the UKCCSG/SIOP prospective study. Lancet Oncol. Aug 2007;8(8):696-705. [Medline].

  9. Heideman RL, Packer RJ, Albright LA. Tumors of the central nervous system. In: Principles and Practice of Pediatric Oncology. 3rd ed. Raven Press; 1997:633-97.

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  17. Sandri A, Massimino M, Mastrodicasa L, et al. Treatment with oral etoposide for childhood recurrent ependymomas. J Pediatr Hematol Oncol. Sep 2005;27(9):486-90. [Medline].

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MRI showing an ependymoma of the fourth ventricle, compressing the cerebellum and brain stem.
Sagittal section of an ependymoma of the fourth ventricle.
Section displaying typical perivascular pseudorosettes of a benign ependymoma.
Section displaying high cellularity, nuclear atypia, and numerous mitoses characteristic of an anaplastic ependymoma.
 
 
 
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