A phase I dose escalation study of imatinib mesylate plus standard-dosed temozolomide in the treatment of patients with malignant glioma

1540 Imatinib mesylate (Gleevec), an inhibitor of the PDGF receptor tyrosine kinase with anti-angiogenic activity, has been shown to decrease tumor interstitial pressure resulting in enhanced delivery of cytotoxic therapy. The current phase I study is designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of imatinib mesylate when combined with temozolomide, a DNA methylator with established anti-glioma activity, in patients with malignant glioma. Eligibility criteria include: histologically confirmed malignant glioma; age at least 18 years; KPS of at least 60%; less than grade 2 intratumoral hemorrhage; adequate hepatic, renal, and bone marrow function and lack of prior failure or significant toxicity following treatment with either imatinib mesylate or temozolomide. Temozolomide is dosed at 200 mg/m2 on days 1–5 of each 28-day cycle. Imatinib mesylate is administered on days 1–8 of each cycle and the dose is escalated in successive cohorts of 3–6 patients via a standard ...