Abstract 3604: Preclinical antitumor study of famitinib, an orally available multi-targeted kinase inhibitor of VEGFR/PDGFR/c-Kit in phase I clinical trials

Angiogenesis plays a key role in tumor progression and anti-angiogenic agents including sunitinib and sorafenib that target VEGF/VEGFR signaling pathway have been proved to an effective therapy for cancer in the clinic. However, severe side effects such as hypertension and bone marrow toxicity limit their clinical application. Thus, development of novel anti-angiogenic agents with fewer side effects is still an unmet challenge. In this study, we characterized the in vitro and in vivo antitumor activity of famitinib, an orally active multi-targeted kinase inhibitor. Famitinib inhibited the activity of c-kit, VEGFR-2, PDGFRα and PDGFRβ with IC50 values of 2.3 nM, 4.7 nM and 6.6 nM, respectively. In addition, Famitinib inhibited the VEGF-induced proliferation, migration and tubule formation of human umbilical vein endothelial cells, and micro-vessel spouting from matrigel-embedded rat aortic rings. In vivo, famitinib exhibited broad and potent anti-tumor activity, leading to regression or growth arrest of various established xenografts derived from human tumor cell lines. Moreover, famitinib significantly enhanced the efficacy of oxaliplatin or 5-fluorouracil when they were combined. In summary, famitinib has potent preclinical antitumor activity which supports its further evaluation in clinic. Famitinib is currently in phase I clinical trials in China. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3604. doi:10.1158/1538-7445.AM2011-3604