BACKGROUND: Hypothalamic-chiasmatic gliomas (HCG) account for up to 20% of tumors in patients under the age of 3 years. While most children respond to chemotherapy, alternative treatment approaches are needed for those with progressive disease refractory to chemotherapy. PROCEDURE: Six patients (median age: 5.5 years) with progressive HCG were treated with imatinib for 3-29 months at a median daily oral dose of 270 mg/m(2). All patients initially presented with extensive tumors during infancy and had undergone two to three surgical resections and two to three prior chemotherapies with multiple agents. RESULTS: The best response achieved was stable disease in all six patients. Disease control lasted from 5 to 46 months and was sustained longer in comparison to their last prior chemotherapy. Toxicities possibly related to imatinib included edema, elevated liver enzymes and bowel problems. Immunohistochemistry in our patients' tumor cells revealed focal expression of arg and PDGFR-alpha in one patient, in the remaining five patients no expression of any of the five known targets of imatinib could be detected. Expression of PDGFR-alpha and PDGFR-beta was detected in endothelial cells of tumor capillaries of all six patients. CONCLUSIONS: We conclude that imatinib has possible activity in progressive HCG and may present an additional therapeutic option for patients who are too young or whose tumor is too extensive to receive radiotherapy. However, the optimal use of imatinib in this disease, its mechanism of action, and possible long-term effects remain unclear and will require additional study. Copyright 2008 Wiley-Liss, Inc.
BACKGROUND:Hypothalamic-chiasmatic gliomas (HCG) account for up to 20% of tumors in patients under the age of 3 years. While most children respond to chemotherapy, alternative treatment approaches are needed for those with progressive disease refractory to chemotherapy. PROCEDURE: Six patients (median age: 5.5 years) with progressive HCG were treated with imatinib for 3-29 months at a median daily oral dose of 270 mg/m(2). All patients initially presented with extensive tumors during infancy and had undergone two to three surgical resections and two to three prior chemotherapies with multiple agents. RESULTS: The best response achieved was stable disease in all six patients. Disease control lasted from 5 to 46 months and was sustained longer in comparison to their last prior chemotherapy. Toxicities possibly related to imatinib included edema, elevated liver enzymes and bowel problems. Immunohistochemistry in our patients' tumor cells revealed focal expression of arg and PDGFR-alpha in one patient, in the remaining five patients no expression of any of the five known targets of imatinib could be detected. Expression of PDGFR-alpha and PDGFR-beta was detected in endothelial cells of tumor capillaries of all six patients. CONCLUSIONS: We conclude that imatinib has possible activity in progressive HCG and may present an additional therapeutic option for patients who are too young or whose tumor is too extensive to receive radiotherapy. However, the optimal use of imatinib in this disease, its mechanism of action, and possible long-term effects remain unclear and will require additional study. Copyright 2008 Wiley-Liss, Inc.