Treatment Options Under Clinical Evaluation
Current Clinical Trials

The therapy for both children and adults with supratentorial high-grade astrocytoma includes surgery, radiation therapy, and chemotherapy. Outcome in high-grade gliomas occurring in childhood may be more favorable than that in adults, but it is not clear if this difference is caused by biologic variations in tumor characteristics, therapies used, tumor resectability, or other factors that are not presently understood.[1] The ability to obtain a complete resection is associated with a better prognosis.[2] Radiation therapy is administered to a field that widely encompasses the entire tumor. Alternatively, it can be administered to the entire brain with a cone down to the tumor volume.[3] The radiation therapy dose to the tumor bed is usually at least 54 Gy. Despite such therapy, overall survival rates remain poor. Among patients treated with surgery, radiation therapy and nitrosourea (lomustine)-based chemotherapy, 5-year progression-free survival was 19% ± 3%; survival was 40% in those who had total resections.[4] In one trial, children with glioblastoma multiforme who were treated on a prospective randomized trial with adjuvant lomustine, vincristine, and prednisone fared better than those children treated with radiation therapy alone.[5] In adults, the addition of temozolomide (Temodal) during and after radiation therapy resulted in improved 2-year event-free survival as compared to treatment with radiation therapy alone. Adult patients with glioblastoma multiforme with a methylated O⁶-methylguanine-DNA-methyltransferase (MGMT) promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not.[6,7] The role of temozolomide given concurrently with radiation therapy for children with supratentorial high-grade gliomas has not yet been demonstrated but is under clinical evaluation. Children younger than 3 years may benefit from chemotherapy to delay, modify, or, in selected cases, obviate the need for radiation therapy.[8,9] Clinical trials that evaluate chemotherapy with or without radiation therapy are ongoing. Information about ongoing clinical trials is available from the NCI Web site.

The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.

• COG-ACNS0423 : The Children's Oncology Group (COG) is conducting a pilot phase II study of adjuvant radiation therapy and temozolomide followed by maintenance temozolomide and lomustine for children with newly diagnosed disease. This is the first of a series of planned phase II studies evaluating agents during and after radiation therapy.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with childhood high-grade cerebral astrocytoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

1. Rasheed BK, McLendon RE, Herndon JE, et al.: Alterations of the TP53 gene in human gliomas. Cancer Res 54 (5): 1324-30, 1994.  [PUBMED Abstract]
   
   
2. 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 89 (1): 52-9, 1998.  [PUBMED Abstract]
   
   
3. Woo SY, Donaldson SS, Cox RS: Astrocytoma in children: 14 years' experience at Stanford University Medical Center. J Clin Oncol 6 (6): 1001-7, 1988.  [PUBMED Abstract]
   
   
4. Fouladi M, Hunt DL, Pollack IF, et al.: Outcome of children with centrally reviewed low-grade gliomas treated with chemotherapy with or without radiotherapy on Children's Cancer Group high-grade glioma study CCG-945. Cancer 98 (6): 1243-52, 2003.  [PUBMED Abstract]
   
   
5. Sposto R, Ertel IJ, Jenkin RD, et al.: The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Childrens Cancer Study Group. J Neurooncol 7 (2): 165-77, 1989.  [PUBMED Abstract]
   
   
6. Stupp R, Mason WP, van den Bent MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (10): 987-96, 2005.  [PUBMED Abstract]
   
   
7. Hegi ME, Diserens AC, Gorlia T, et al.: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352 (10): 997-1003, 2005.  [PUBMED Abstract]
   
   
8. Duffner PK, Horowitz ME, Krischer JP, et al.: Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 328 (24): 1725-31, 1993.  [PUBMED Abstract]
   
   
9. Duffner PK, Krischer JP, Burger PC, et al.: Treatment of infants with malignant gliomas: the Pediatric Oncology Group experience. J Neurooncol 28 (2-3): 245-56, 1996 May-Jun.  [PUBMED Abstract]
   
   

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