Imatinib (STI 571) is active in patients (PTS) with high-grade gliomas progressing on standard therapy

Katz, Artur; Barrios, Carlos H.; Abramoff, Roberto; Simon, Sérgio Daniel; Tabacof, Jacques; Gansl, Rene Claúdio

doi:10.1200/jco.2004.22.14_suppl.1542

Cited by 7 publications

(2 citation statements)

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“…Similar to the current study, these reports noted a small, but intriguing, incidence of objective responses, which were observed in 4 of 52 patients and 4 of 15 patients, respectively, in the two studies that administered imatinib alone (Katz et al, 2004;Raymond et al, 2004), and 5 of 26 patients who received imatinib with hydroxyurea (Dresemann et al, 2004). However, given the phase I nature of the current study, no conclusions can be made regarding efficacy.…”

Section: Discussionsupporting

confidence: 71%

“…Of note, several preliminary studies conducted in Europe for adults with recurrent malignant gliomas, in which imatinib was administered either alone (Katz et al, 2004;Raymond et al, 2004) or with hydroxyurea (Dresemann et al, 2004), noted a low incidence of symptomatic hemorrhages. Similar to the current study, these reports noted a small, but intriguing, incidence of objective responses, which were observed in 4 of 52 patients and 4 of 15 patients, respectively, in the two studies that administered imatinib alone (Katz et al, 2004;Raymond et al, 2004), and 5 of 26 patients who received imatinib with hydroxyurea (Dresemann et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

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Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: A Pediatric Brain Tumor Consortium report1

et al. 2007

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This study estimated the maximum tolerated dose (MTD) of imatinib with irradiation in children with newly diagnosed brainstem gliomas, and those with recurrent malignant intracranial gliomas, stratified according to use of enzyme-inducing anticonvulsant drugs (EIACDs). In the brainstem glioma stratum, imatinib was initially administered twice daily during irradiation, but because of possible association with intratumoral hemorrhage (ITH) was subsequently started two weeks after irradiation. The protocol was also amended to exclude children with prior hemorrhage. Twenty-four evaluable patients received therapy before the amendment, and three of six with a brainstem tumor experienced dose-limiting toxicity (DLT): one had asymptomatic ITH, one had grade 4 neutropenia and, one had renal insufficiency. None of 18 patients with recurrent glioma experienced DLT. After protocol amendment, 3 of 16 patients with brainstem glioma and 2 of 11 patients with recurrent glioma who were not receiving EIACDs experienced ITH DLTs, with three patients being symptomatic. In addition to the six patients with hemorrhages during the DLT monitoring period, 10 experienced ITH (eight patients were symptomatic) thereafter. The recommended phase II dose for brainstem gliomas was 265 mg/m(2). Three of 27 patients with brainstem gliomas with imaging before and after irradiation, prior to receiving imatinib, had new hemorrhage, excluding their receiving imatinib. The MTD for recurrent high-grade gliomas without EIACDs was 465 mg/m(2), but the MTD was not established with EIACDs, with no DLTs at 800 mg/m(2). In summary, recommended phase II imatinib doses were determined for children with newly diagnosed brainstem glioma and recurrent high-grade glioma who were not receiving EIACDs. Imatinib may increase the risk of ITH, although the incidence of spontaneous hemorrhages in brainstem glioma is sufficiently high that this should be considered in studies of agents in which hemorrhage is a concern.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: A Pediatric Brain Tumor Consortium report1

et al. 2007

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Molecularly Targeted Therapy for Pediatric Brain Tumors

2005

J Neurooncol

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Treatment of pediatric brain tumors remains a challenge because of the toxicity associated with conventional treatment and the relative resistance of tumors at the time of recurrence. The traditional approach of administering cytotoxic agents at the maximum tolerated dose is being supplanted by the development of molecularly targeted agents aimed at critical cellular changes that are responsible for the growth and spread of cancer cells. These agents theoretically should be more specific for tumor cells and less toxic to normal cells. While the idea of targeted therapy has generated much excitement in the oncology community, the degree of benefit to patients with central nervous system (CNS) tumors remains unclear. Numerous challenges remain in the development of these agents, including identification of meaningful targets, delivery of agents in sufficient quantity at the target site, and determination of any biologic response to these agents. This article discusses the rationale behind several of these agents and their use in pediatric patients with brain tumors.

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