Pediatric Astrocytoma Medication

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

Medication Summary

Current investigational dosing chemotherapy regimens for the treatment of low-grade astrocytomas with carboplatin and vincristine and for the treatment of high-grade astrocytomas with temozolomide,[7] carmustine (BCNU), and cisplatin are provided below.

Next

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 from chemotherapy more quickly than malignant ones and is the rationale behind current cyclic dosage schedules.

Antineoplastic agents interfere with cell reproduction. Some agents are cell cycle specific, while 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.

View full drug information

Temozolomide (Temodar)

 

Prodrug that is hydrolyzed to MTIC at physiologic pH. Exerts its effect by site-specific DNA cross-linking resulting from the methylation guanine at the O6 and N7 positions. Bioavailability is 100%; approximately 35% crosses the blood-brain barrier.

View full drug information

Carboplatin (Paraplatin)

 

Analog of cisplatin. This is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA crosslinks and inhibition of DNA replication.

View full drug information

Vincristine (Oncovin)

 

Plant-derived vinca alkaloid. Acts as a mitotic inhibitor by binding tubulin.

View full drug information

Carmustine (BiCNU)

 

This DNA alkylator causes interstrand and intrastrand DNA crosslinks, resulting in damage to the DNA template and inhibition of DNA replication.

View full drug information

Cisplatin (Platinol)

 

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

Previous
Proceed to Follow-up
 
 
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

  1. Hales RK, Shokek O, Burger PC, Paynter NP, Chaichana KL, Quiñones-Hinojosa A, et al. Prognostic factors in pediatric high-grade astrocytoma: the importance of accurate pathologic diagnosis. J Neurooncol. Aug 2010;99(1):65-71. [Medline].

  2. Tihan T, Ersen A, Qaddoumi I, Sughayer MA, Tolunay S, Al-Hussaini M, et al. Pathologic characteristics of pediatric intracranial pilocytic astrocytomas and their impact on outcome in 3 countries: a multi-institutional study. Am J Surg Pathol. Jan 2012;36(1):43-55. [Medline].

  3. Belirgen M, Berrak SG, Ozdag H, Bozkurt SU, Eksioglu-Demiralp E, Ozek MM. Biologic tumor behavior in pilocytic astrocytomas. Childs Nerv Syst. Mar 2012;28(3):375-89. [Medline].

  4. Chintagumpala MM, Friedman HS, Stewart CF, et al. A phase II window trial of procarbazine and topotecan in children with high-grade glioma: a report from the children's oncology group. J Neurooncol. Apr 2006;77(2):193-8. [Medline].

  5. Geyer JR, Sposto R, Jennings M, et al. Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group. J Clin Oncol. Oct 20 2005;23(30):7621-31. [Medline].

  6. Pollack IF, Hamilton RL, Sobol RW, et al. O6-methylguanine-DNA methyltransferase expression strongly correlates with outcome in childhood malignant gliomas: results from the CCG-945 Cohort. J Clin Oncol. Jul 20 2006;24(21):3431-7. [Medline].

  7. Akyüz C, Demir HA, Varan A, Yalçin B, Kutluk T, Büyükpamukçu M. Temozolomide in relapsed pediatric brain tumors: 14 cases from a single center. Childs Nerv Syst. Jan 2012;28(1):111-5. [Medline].

  8. Bouffet E, Jakacki R, Goldman S, et al. Phase II Study of weekly vinblastine in recurrent/refractory pediatric low-grade gliomas. Neuro-Oncology. 2008;10(3):450.

  9. Bredel M, Pollack IF, Hamilton RL, James CD. Epidermal growth factor receptor expression and gene amplification in high-grade non-brainstem gliomas of childhood. Clin Cancer Res. Jul 1999;5(7):1786-92. [Medline].

  10. Cokgor I, Friedman AH, Friedman HS. Gliomas. Eur J Cancer. Nov 1998;34(12):1910-5; discussion 1916-8. [Medline].

  11. Fernandez C, Figarella-Branger D, Girard N, et al. Pilocytic astrocytomas in children: prognostic factors--a retrospective study of 80 cases. Neurosurgery. Sep 2003;53(3):544-53; discussion 554-5. [Medline].

  12. Finlay JL, Boyett JM, Yates AJ, et al. Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group. J Clin Oncol. Jan 1995;13(1):112-23. [Medline].

  13. Finlay JL, Wisoff JH. The impact of extent of resection in the management of malignant gliomas of childhood. Childs Nerv Syst. Nov 1999;15(11-12):786-8. [Medline].

  14. Gilbertson RJ, Hill DA, Hernan R, et al. ERBB1 is amplified and overexpressed in high-grade diffusely infiltrative pediatric brain stem glioma. Clin Cancer Res. Sep 1 2003;9(10 Pt 1):3620-4. [Medline].

  15. Grill J, Couanet D, Cappelli C, et al. Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma. Ann Neurol. Mar 1999;45(3):393-6. [Medline].

  16. Gururangan S, Fisher MJ, Allen JC, Herndon JE 2nd, Quinn JA, Reardon DA, et al. Temozolomide in children with progressive low-grade glioma. Neuro Oncol. Apr 2007;9(2):161-8. [Medline].

  17. Guthrie BL, Laws ER Jr. Supratentorial low-grade gliomas. Neurosurg Clin N Am. Jan 1990;1(1):37-48. [Medline].

  18. Huncharek M, Wheeler L, McGarry R, Geschwind JF. Chemotherapy response rates in recurrent/progressive pediatric glioma; results of a systematic review. ALYSIS. Jul-Aug 1999;19(4C):3569-74. [Medline].

  19. Jacobson DM. Gliomas of the anterior visual pathways. Neurosurg Clin N Am. Oct 1999;10(4):683-98, ix. [Medline].

  20. Khatua S, Peterson KM, Brown KM, et al. Overexpression of the EGFR/FKBP12/HIF-2alpha pathway identified in childhood astrocytomas by angiogenesis gene profiling. Cancer Res. Apr 15 2003;63(8):1865-70. [Medline].

  21. Khaw SL, Coleman LT, Downie PA, Heath JA, Ashley DM. Temozolomide in pediatric low-grade glioma. Pediatr Blood Cancer. Nov 2007;49(6):808-11. [Medline].

  22. Komotar RJ, Mocco J, Carson BS, et al. Pilomyxoid astrocytoma: a review. MedGenMed. 2004;6(4):42. [Medline].

  23. Kuo DJ, Weiner HL, Wisoff J, et al. Temozolomide is active in childhood, progressive, unresectable, low-grade gliomas. J Pediatr Hematol Oncol. May 2003;25(5):372-8. [Medline].

  24. Lafay-Cousin L, Holm S, Qaddoumi I, et al. Weekly vinblastine in pediatric low-grade glioma patients with carboplatin allergic reaction. Cancer. Jun 15 2005;103(12):2636-42. [Medline].

  25. MacDonald TJ, Arenson EB, Ater J, et al. Phase II study of high-dose chemotherapy before radiation in children with newly diagnosed high-grade astrocytoma: final analysis of Children's Cancer Group Study 9933. Cancer. Dec 15 2005;104(12):2862-71. [Medline].

  26. Nadkarni TD, Rekate HL. Pediatric intramedullary spinal cord tumors. Critical review of the literature. Childs Nerv Syst. Jan 1999;15(1):17-28. [Medline].

  27. Nicholson HS, Krailo M, Ames MM, et al. Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children's Cancer Group. J Clin Oncol. Sep 1998;16(9):3037-43. [Medline].

  28. Packer RJ. Brain tumors in children. Arch Neurol. Apr 1999;56(4):421-5. [Medline].

  29. Pencalet P, Maixner W, Sainte-Rose C, et al. Benign cerebellar astrocytomas in children. J Neurosurg. Feb 1999;90(2):265-73. [Medline].

  30. Pollack IF. The role of surgery in pediatric gliomas. J Neurooncol. May 1999;42(3):271-88. [Medline].

  31. Pollack IF, Boyett JM, Finlay JL. Chemotherapy for high-grade gliomas of childhood. Childs Nerv Syst. Oct 1999;15(10):529-44. [Medline].

  32. Pollack IF, Finkelstein SD, Woods J, et al. Expression of p53 and prognosis in children with malignant gliomas. N Engl J Med. Feb 7 2002;346(6):420-7. [Medline].

  33. Prados MD, Edwards MS, Rabbitt J, Lamborn K, Davis RL, Levin VA. Treatment of pediatric low-grade gliomas with a nitrosourea-based multiagent chemotherapy regimen. J Neurooncol. May 1997;32(3):235-41. [Medline].

  34. Reddy AT, Packer RJ. Chemotherapy for low-grade gliomas. Childs Nerv Syst. Oct 1999;15(10):506-13. [Medline].

  35. Rubin G, Michowitz S, Horev G, et al. Pediatric brain stem gliomas: an update. Childs Nerv Syst. Apr-May 1998;14(4-5):167-73. [Medline].

  36. Sharif S, Ferner R, Birch JM, et al. Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy. J Clin Oncol. Jun 1 2006;24(16):2570-5. [Medline].

  37. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. Mar 10 2005;352(10):987-96. [Medline].

  38. Thorarinsdottir HK, Rood B, Kamani N, et al. Outcome for children < 4 years of age with malignant central nervous system tumors treated with high-dose chemotherapy and autologous stem cell rescue. Pediatr Blood Cancer. Feb 2 2006;[Medline].

  39. Vredenburgh JJ, Desjardins A, Herndon JE 2nd, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. Oct 20 2007;25(30):4722-9. [Medline].

  40. Wisoff JH, Boyett JM, Berger MS, et al. Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children's Cancer Group trial no. CCG-945. J Neurosurg. Jul 1998;89(1):52-9. [Medline].

 
Previous
Next
 
This MRI shows a juvenile pilocytic astrocytoma of the cerebellum.
This MRI shows a supratentorial glioblastoma multiforme.
This section displays the typical biphasic pattern of a juvenile pilocytic astrocytoma, consisting of dense, relatively anuclear, fibrillar areas alternating with looser cystic fields.
This section displays the high cellularity, mitosis, and nuclear atypia characteristic of an anaplastic astrocytoma (grade III).
This section displays a typical field of a glioblastoma multiforme (grade IV) with pseudopalisading neovascularity, nuclear atypia, numerous mitoses, and areas of hemorrhage.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.