Thema: News: Gleevec in patients with recurrent glioblastoma
News: Gleevec in patients with recurrent glioblastoma
Karen[a]
08.06.2004 22:29:43
Multicentre phase II study of imatinib mesylate in patients with recurrent glioblastoma: An EORTC: NDDG/BTG Intergroup Study.
Abstract No: 1501
Author(s): E. Raymond, A. Brandes, A. Van Oosterom, C. Dittrich, P. Fumoleau, B. Coudert, C. Twelves, C. De Balincourt, D. Lacombe, M. Van Den Bent; EORTC, Brussels, Belgium
Background:
Autocrine activation of PDGFα&β receptors yields strong mitogenic effects and activates tumor angiogenesis in malignant gliomas. Preclinical data showed tumor growth inhibition of ras and v-sis transformed BALB/c, 3T3U87 and U343 human glioma xenografts in mice using imatinib mesylate.
Methods:
To assess the antitumor activity (measured by response and 6-month PFS) and the safety of imatinib mesylate (Glivec) in patients (pts) with histologically proven, CT-scan or MRI documented measurable recurrent glioblastoma, stable/decreasing doses of steroids, no more than one prior chemotherapy regimen, and no surgery or radiotherapy within 3 months prior to enrollment were entered. Imatinib mesylate was given until tumor progression at the daily dose of 600mg (group A) and 800mg (group B) in two cohorts of pts. A Fleming one sample/one stage testing procedure was used.
Results:
A total of 51 pts (M/F: 26/25; median age: 54, range: 27-68; PS 0/1/2: 18/26/7) were entered. 33 pts had been exposed to chemotherapy, 50 to radiotherapy, and 45 had prior resection. 19 pts were entered in group A (70 cycles) and 32 in group B (113 cycles). Grade 3-4 neutropenia was reported in 5 pts (1 in group A and 4 in group B) and was associated with fever in 3 pts. Dose reduction:5 pts (4 in group A, 1 in group B); dose interruption: 21 pts (11 in group A, 10 in group B) pts. Grade 3-4 non hematological toxicity consisted of edema (1 pt), skin rash (2 pts), and reversible ALT elevation (4 pts). One patient presented an intratumoral hemorrhage associated with a documented tumor progression (considered not related to treatment). Three pts (2 in group A and 1 in group B) experienced confirmed partial responses that lasted 10, 10, and 12+ months. Responses slowly occurred after 3, 6 and 7 months of drug exposure. Prolonged >6-months tumor stabilizations were reported in 5 pts (1 in group A and 4 in group B).
Conclusion; Imatinib mesylate as single agent displays promising antitumor activity and good safety profile in patients with recurrent glioblastoma. This study is currently extended to patients with malignant oligodendroglioma and anaplastic astrocytoma.
Event: 2004 ASCO Annual Meeting
Presenter: Eric Raymond, MD, PhD
Abstract No: 1501
Author(s): E. Raymond, A. Brandes, A. Van Oosterom, C. Dittrich, P. Fumoleau, B. Coudert, C. Twelves, C. De Balincourt, D. Lacombe, M. Van Den Bent; EORTC, Brussels, Belgium
Background:
Autocrine activation of PDGFα&β receptors yields strong mitogenic effects and activates tumor angiogenesis in malignant gliomas. Preclinical data showed tumor growth inhibition of ras and v-sis transformed BALB/c, 3T3U87 and U343 human glioma xenografts in mice using imatinib mesylate.
Methods:
To assess the antitumor activity (measured by response and 6-month PFS) and the safety of imatinib mesylate (Glivec) in patients (pts) with histologically proven, CT-scan or MRI documented measurable recurrent glioblastoma, stable/decreasing doses of steroids, no more than one prior chemotherapy regimen, and no surgery or radiotherapy within 3 months prior to enrollment were entered. Imatinib mesylate was given until tumor progression at the daily dose of 600mg (group A) and 800mg (group B) in two cohorts of pts. A Fleming one sample/one stage testing procedure was used.
Results:
A total of 51 pts (M/F: 26/25; median age: 54, range: 27-68; PS 0/1/2: 18/26/7) were entered. 33 pts had been exposed to chemotherapy, 50 to radiotherapy, and 45 had prior resection. 19 pts were entered in group A (70 cycles) and 32 in group B (113 cycles). Grade 3-4 neutropenia was reported in 5 pts (1 in group A and 4 in group B) and was associated with fever in 3 pts. Dose reduction:5 pts (4 in group A, 1 in group B); dose interruption: 21 pts (11 in group A, 10 in group B) pts. Grade 3-4 non hematological toxicity consisted of edema (1 pt), skin rash (2 pts), and reversible ALT elevation (4 pts). One patient presented an intratumoral hemorrhage associated with a documented tumor progression (considered not related to treatment). Three pts (2 in group A and 1 in group B) experienced confirmed partial responses that lasted 10, 10, and 12+ months. Responses slowly occurred after 3, 6 and 7 months of drug exposure. Prolonged >6-months tumor stabilizations were reported in 5 pts (1 in group A and 4 in group B).
Conclusion; Imatinib mesylate as single agent displays promising antitumor activity and good safety profile in patients with recurrent glioblastoma. This study is currently extended to patients with malignant oligodendroglioma and anaplastic astrocytoma.
Event: 2004 ASCO Annual Meeting
Presenter: Eric Raymond, MD, PhD
Karen[a]
