Anne[a]
ASCO 2005 Abstract No: 1515
Imatinib Mesylate (Gleevec) Plus Hydroxyurea is an Effective Regimen in the Treatment of Recurrent Malignant Glioma. Phase 2 Study Results.
H. S. Friedman, J. Quinn, J. Rich, J. Vredenburgh, A. Desjardins, S. Sathornsumetee, A. Salvado, Z. Nikolova, D. Bigner, D. Reardon
Abstract: 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.