Phase I and Pharmacokinetic Study of Daily Oral AZD2171, an Inhibitor of Vascular Endothelial Growth Factor Tyrosine Kinases, in Combination With Carboplatin and Paclitaxel in Patients With Advanced Non–Small-Cell Lung Cancer: The National Cancer Institute of Canada Clinical Trials Group

Purpose AZD2171 is a potent inhibitor of vascular endothelial growth factor receptors that showed broad antitumor activity in preclinical models. Doses of up to 45 mg/d of AZD2171 are tolerable when administered alone. This study evaluated escalating doses of AZD2171 in combination with standard chemotherapy in patients with advanced non–small-cell lung cancer. Patients and Methods Eligible patients received carboplatin targeted to an area under the concentration time curve of 6 mg · min/mL and paclitaxel 200 mg/m2, both on day 1 of a 3-week cycle; daily oral AZD2171 at either 30 mg or 45 mg commenced day 2 of cycle 1. Pharmacokinetics of all drugs were performed, and tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Results Twenty patients were enrolled. No dose-limiting toxicities were observed during cycle 1 at either dose. Fatigue, diarrhea, anorexia, and granulocytopenia were common; hypertension was manageable with a treatment algorithm designed for this protocol....