A phase I/II trial of PTK787/ZK 222584 (PTK/ZK), a novel, oral angiogenesis inhibitor, in combination with either temozolomide or lomustine for patients with recurrent glioblastoma multiforme (GBM)

1513 Background: VEGF-mediated signaling through VEGF receptors is integral to GBM neovascularization and therefore an attractive therapeutic target. PTK/ZK is an oral, once-daily inhibitor of all known VEGF receptors. The primary objective of this trial was to determine the safety profile and maximum tolerated dose (MTD) of oral once-daily PTK/ZK in combination with either temozolomide (TMZ) or lomustine (CCNU) in patients (pts) with GBM. Antitumor activity was also assessed. Methods: The starting dose of PTK/ZK was 500 mg/day, escalating to 1,000, 1,250, and 1,500 mg/day in cohorts of 3 to 6 pts with dose expansion at 1,500 mg/day in the TMZ treatment arm. Concurrently, pts also received either TMZ (200 mg/m2/day for 5 days every 28 days) or CCNU (130 mg/m2 every 6 weeks). Results: Among 60 pts enrolled, median age was 53 years (range, 28 - 80 years), median KPS was 90 (range, 70 - 100), and the median number of prior regimens was 1 (range, 1 - 9). In 37 pts treated with PTK/ZK + TMZ, 1 dose-limiting to...