Clinical and dynamic imaging results of the first phase I study of AG–013736, an oral anti-angiogenesis agent, in patients (pts) with advanced solid tumors

2503 Background: AG-013736 is a potent and selective inhibitor of VEGF and PDGF receptor tyrosine kinases with broad preclinical activity in xenograft models of solid tumors. Methods: The primary objective was to determine maximum tolerated dose (MTD) and safety. Efficacy, pharmacokinetics (PK), and tumor vascular response were also evaluated. AG–013736 was administered orally once or twice daily in 28-day cycles in escalating doses to pts with solid tumors. Results: 36 pts in 6 cohorts were treated. At least 2 cycles of data are available on the first 30. Tumor diagnoses: breast (11), thyroid (5), renal cell (5), lung (4), and other (5). The MTD was 5 mg twice daily (BID) fasted (no food or beverage within 2 hours of dose). Toxicity: Dose-limiting toxicities (DLTs) at doses >MTD (16 pts) were hypertension (HTN) (6 pts); seizures associated with HTN (2); elevated liver function tests (2); mesenteric vein thrombosis and pancreatitis (1); and stomatitis (2). One pt with a cavitating lung lesion died of hemo...