Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study.
OBJECTIVE
To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas.


METHODS
This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging. Three different histologic groups were studied: glioblastomas (GBM), pure/mixed (anaplastic) oligodendrogliomas (OD), and low-grade or anaplastic astrocytomas (A). Imatinib was started at a dose of 600 mg/d with dose escalation to 800 mg in case of no toxicity; during the trial this dose was increased to 800 mg/d with escalation to 1,000 mg/d. Trial design was one-stage Fleming; both an objective response and 6 months of progression-free survival (PFS) were considered a successful outcome to treatment.


RESULTS
A total of 112 patients (51 patients with GBM, 25 patients with A, and 36 patients with OD) were enrolled. Imatinib was in general well tolerated. The median number of cycles was 2.0 (range, 1 to 43 cycles). Five patients had an objective partial response, including three patients with GBM; all had 6 months of PFS. The 6-month PFS rate was 16% (95% CI, 8.0% to 34.0%) in GBM, 4.0% (95% CI, 0.3% to 15.0%) in OD, and 9% (95% CI, 2.0% to 25.0%) in A. The exposure to imatinib was significantly lower in patients using enzyme-inducing antiepileptic drugs. The presence of ABCG2 point mutations were not correlated with pharmacokinetic findings. No somatic activating mutations of KIT or platelet-derived growth factor receptor-A or -B were found.


CONCLUSIONS
In the dose range of 600 to 1,000 mg/d, single-agent imatinib is well tolerated but has limited antitumor activity in patients with recurrent gliomas.
Raymond
Eric
E
Service Inter Hospitalier de Cancérologie, Beaujon University Hospital, Clichy.
Brandes
Alba A
AA
Dittrich
Christian
C
Fumoleau
Pierre
P
Coudert
Bruno
B
Clement
Paul M J
PM
Frenay
Marc
M
Rampling
Roy
R
Stupp
Roger
R
Kros
Johan M
JM
Heinrich
Michael C
MC
Gorlia
Thierry
T
Lacombe
Denis
D
van den Bent
Martin J
MJ
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D000068877:Imatinib Mesylate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate