TY - JOUR
T1 - A phase II window trial of procarbazine and topotecan in children with high-grade glioma
T2 - A report from the children's oncology group
AU - Chintagumpala, Murali M.
AU - Friedman, Henry S.
AU - Stewart, Clinton F.
AU - Kepner, James
AU - McLendon, Roger E.
AU - Modrich, Paul L.
AU - McCluggage, Charles
AU - Burger, Peter
AU - Holmes, Emi
AU - Thompson, Stephen
AU - Rutka, James
AU - Michalski, Jeff
AU - Woo, Shiao
AU - Blaney, Susan M.
AU - Kun, Larry E.
AU - Horowitz, Marc E.
PY - 2006/4
Y1 - 2006/4
N2 - The role of chemotherapy in the treatment of high-grade gliomas in children is unclear. Early reports were suggestive of improved outcome in children with high-grade glioma with the addition of chemotherapy after surgery and radiation therapy. Subsequent studies did not show similar favorable contribution of chemotherapy to the outcome of these children. Further efforts to identify active chemotherapy agents in children include use of agents that have shown efficacy in adult patients with high-grade glioma and agents that have shown promise in mice bearing human xenografts of brain tumors. A Pediatric Oncology Group (POG 9431) trial tested the activity of two such agents, procarbazine and topotecan in newly diagnosed patients with high-grade glioma who had measurable disease after diagnostic surgery. Neither agent showed efficacy within the confines of the statistical design of the study. This study showed that children with high-grade glioma have an innate resistance to alkylating agents based on mismatch repair deficiency and high levels of alkyguanine transferase (AGT). Future trials should consider strategies to overcome the resistance mechanisms in children with high-grade glioma.
AB - The role of chemotherapy in the treatment of high-grade gliomas in children is unclear. Early reports were suggestive of improved outcome in children with high-grade glioma with the addition of chemotherapy after surgery and radiation therapy. Subsequent studies did not show similar favorable contribution of chemotherapy to the outcome of these children. Further efforts to identify active chemotherapy agents in children include use of agents that have shown efficacy in adult patients with high-grade glioma and agents that have shown promise in mice bearing human xenografts of brain tumors. A Pediatric Oncology Group (POG 9431) trial tested the activity of two such agents, procarbazine and topotecan in newly diagnosed patients with high-grade glioma who had measurable disease after diagnostic surgery. Neither agent showed efficacy within the confines of the statistical design of the study. This study showed that children with high-grade glioma have an innate resistance to alkylating agents based on mismatch repair deficiency and high levels of alkyguanine transferase (AGT). Future trials should consider strategies to overcome the resistance mechanisms in children with high-grade glioma.
KW - AGT activity in high-grade glioma in children
KW - High-grade glioma in children
KW - Mismatch repair proteins in high-grade glioma in children
KW - Phase II window therapy in high-grade glioma in children
KW - Procarbazine in high-grade glioma in children
KW - Resistance mechanisms in high-grade glioma in children
KW - Topotecan in high-grade glioma in children
UR - http://www.scopus.com/inward/record.url?scp=33747815410&partnerID=8YFLogxK
U2 - 10.1007/s11060-005-9024-x
DO - 10.1007/s11060-005-9024-x
M3 - Article
C2 - 16314955
AN - SCOPUS:33747815410
SN - 0167-594X
VL - 77
SP - 193
EP - 198
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 2
ER -