BACKGROUND: Anlotinib is a novel multi-target tyrosine kinase inhibitor that is 
designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret. We 
aimed to evaluate the safety, pharmacokinetics, and antitumor activity of 
anlotinib in patients with advanced refractory solid tumors.
METHODS: Anlotinib (5-16 mg) was orally administered in patients with solid 
tumor once a day on two schedules: (1) four consecutive weeks (4/0) or (2) 
2-week on/1-week off (2/1). Pharmacokinetic sampling was performed in all 
patients. Twenty-one patients were further enrolled in an expanded cohort study 
on the recommended dose and schedule. Preliminary tumor response was also 
assessed.
RESULTS: On the 4/0 schedule, dose-limiting toxicity (DLT) was grade 3 
hypertension at 10 mg. On the 2/1 schedule, DLT was grade 3 hypertension and 
grade 3 fatigue at 16 mg. Pharmacokinetic assessment indicated that anlotinib 
had long elimination half-lives and significant accumulation during multiple 
oral doses. The 2/1 schedule was selected, with 12 mg once daily as the maximum 
tolerated dose for the expanding study. Twenty of the 21 patients (with colon 
adenocarcinoma, non-small cell lung cancer, renal clear cell cancer, medullary 
thyroid carcinoma, and soft tissue sarcoma) were assessable for antitumor 
activity of anlotinib: 3 patients had partial response, 14 patients had stable 
disease including 12 tumor burden shrinkage, and 3 had disease progression. The 
main serious adverse effects were hypertension, triglyceride elevation, 
hand-foot skin reaction, and lipase elevation.
CONCLUSIONS: At the dose of 12 mg once daily at the 2/1 schedule, anlotinib 
displayed manageable toxicity, long circulation, and broad-spectrum antitumor 
potential, justifying the conduct of further studies.