Efficacy of imatinib mesylate plus hydroxyurea regimen in the treatment of recurrent malignant glioma: Phase II study results

Abstract

1515 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. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis