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Multicentre phase II study
of imatinib mesylate in patients with recurrent glioblastoma: An EORTC: NDDG/BTG
Intergroup Study
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.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-002771,00.asp
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