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Efficacy of imatinib mesylate plus
hydroxyurea regimen in the treatment of recurrent malignant glioma:
Phase II study results
H. S. Friedman, J.
Quinn, J. Rich, J. Vredenburgh, A.
Desjardins, S. Sathornsumetee, A. Salvado,
Z. Nikolova, D. Bigner and D. Reardon
Duke Medcl Ctr, Durham, NC; Novartis
Pharm Corp, East Hanover, NJ; Duke Med, Durham, NC
In this phase 2 study we evaluated the
activity of imatinib mesylate (Gleevec), an inhibitor of
the PDGF receptor tyrosine kinase with anti-angiogenic
activity and the ability to decrease tumor interstitial
pressure, combined with hydroxyurea in the treatment of
patients with recurrent malignant glioma.
Eligibility criteria include: recurrent malignant glioma;
age > 18 years; KPS 60% or greater; less than grade 2
intratumoral hemorrhage; adequate hepatic, renal, and bone
marrow function.
Hydroxyurea is administered at 500 mg BID while Gleevec is
administered at 500 mg BID for patients on enzyme-inducing
anticonvulsants (EIAC; phenytoin, carbamazepine and
phenobarbitol) and at 400 mg QD for those not on
EIAC.
A treatment cycle lasted 28 days and evaluations for
response were performed after every other cycle.
Enrollment includes 64 patients: 32 with recurrent GBM and
32 with recurrent AA/AO.
The median age is 46 (range 21 to 68); 55% are male and 45%
are on EIAC.
All patients had prior XRT and the median number of prior
chemotherapy agents was 3 (range, 1–5) while the median
number of prior progressions was 2 (range, 1–7).
Toxicity has included grade 3 or 4 hematologic events in
20% and 5% respectively, grade 3 edema in 8% and grade 3
LFT abnormalities in 3%.
Nine percent of GBM patients achieved a radiographic
response while 35% achieved stable disease.
Median progression free survival (PFS) for patients with
recurrent AA/AO and GBM are 10.9 and 14.4 weeks respectively.
At 6 months, 26.3% of GBM patients are progression free.
Among heavily pretreated patients with recurrent GBM
enrolled on this study, the rate of radiographic response,
median PFS and 6-mth PFS rate compare favorably to results
achieved with temozolomide in first relapse indicating that
a randomized trial of imatinib mesylate plus hydroxyurea
versus temozolomide is warranted.
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