Safety, pharmacokinetic, and antitumor activity of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors.

e13586 Background: To establish the safety, pharmacokinetics, recommended dose, and antitumor activity of anlotinib, a novel oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors. Methods: Anlotinib was given orally once a day for consecutive 4 weeks or 2 weeks on/1 week off. In consecutive dose group, 5mg/d (n = 4) and 10mg/d (n = 4) was explored; in 2 weeks on/1 week off group, 10mg/d (n = 3), 16mg/d (n = 3), and 12mg/d (n = 21) was explored. Human plasma and urine samples were analyzed by liquid chromatography-mass spectrometry. Results: Dose-limiting toxicities (DLT) at the 10mg/d for consecutive 4 weeks group was grade 3 hypertension, and significant accumulation of anlotinib was observed. For 2 weeks on/1 week off group, DLT were grade 3 hypertension and grade 3 fatigue at the dose of 16 mg/d, the maximum-tolerated doses (MTD) was 12mg/d, the plasma concentration of anlotinib was well controlled. Anlotinib reached its maximum plasma concentration with Tmax of...