|
|
Multicentre phase II study of imatinib
mesylate in patients with recurrent anaplastic oligodendroglioma
(AOD)/mixed oligoastrocytoma (MOA) and anaplastic astrocytoma (AA)/low
grade astrocytoma (LGA): An EORTC New Drug Development Group (NDDG)
and Brain Tumor Group (BTG) study
M. van den Bent, A.
Brandes, M. Frenay, P. Fumoleau, R.
Stupp, C. Dittrich, B. Coudert, P.
Clement, D. Lacombe and E. Raymond
EORTC NDDG/BTG/Data Ctr, Brussels,
Belgium
Background. Autocrine
activation of PDGFα&ß 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 in patients (pts) with histologically
proven, CT-scan or MRI documented measurable recurrent non GBM
tumors, stable/decreasing doses of steroids, no more than one
prior chemotherapy regimen given either in adjuvant or first
line treatment, 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 and 800mg in
two cohorts of pts, group1: AOD/MOA and group 2: AA/LGA.
A Fleming one sample/one stage
testing procedure was used for each cohort
independantly.
Results. G3–4
neutropenia was reported in 1 patient (pt).
Non hematological toxicity
consisted of G3 fatigue in 3 pts, G3 vomiting in 1 pt,
G2–3 liver enzyme disturbances in 6 pts, G1 palpebral
edema was reported in 3 pts and G1 lower limb edema in 2
pts.
Dose reduction: 4 pts;
dose interruption: 6 pts. 35 patients are off-treatment, one
was stable for more than 6 months.
25 are still too early to
evaluate.
The trial is closed for
accrual.
Conclusions. Imatinib
mesylate as single agent displays a good safety profile in
patients with AOD/MOD and AA/LGA.
Final results including response
rates and survival will be presented at the meeting.
|
Group 1 (N= 36)
|
Group 2 (N= 25)
|
|
Gender: M/F/missing
|
20/9/7
|
11/4/10
|
|
Median age
|
47[23-67]
|
37[19-72]
|
|
PS (0/1/2)
|
13/17/6
|
10/10/5
|
|
Prior treatment
Surgery
Radiotherapy
Adjuvant chemotherapy
First line chemotherapy
|
36
36
10
26
|
25
25
3
22
|
|
