Phase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumors

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dc.contributor.authorSyed, Shariq
dc.date.accessioned2014-12-22T05:44:41Z
dc.date.available2014-12-22T05:44:41Z
dc.date.issued2011
dc.description.abstractBackground: This study was designed to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of brivanib in patients with advanced/metastatic solid tumors. Patients and methods: Ninety patients enrolled in this two-part, phase I open-label study of oral brivanib alaninate. The primary objectives of this study were (in part A) dose-limiting toxicity, maximum tolerated dose (MTD) and the lowest biologically active dose level and (in part B) the optimal dose/dose range. The secondary objectives of this study were preliminary evidence of antitumor activity, PK and PD. Results: Across part A (open-label dose escalation and MTD) and part B (open-label dose optimization), 68 patients received brivanib alaninate. Brivanib demonstrated a manageable toxicity profile at doses of 180–800 mg. Most toxic effects were mild. Systemic exposure of the active moiety brivanib increased linearly £1000 mg/day. The MTD was 800 mg/day. Forty-four patients were treated at the MTD: 20 with 800 mg continuously, 11 with 800 mg intermittently and 13 with 400 mg b.i.d. doses. Partial responses were confirmed in two patients receiving brivanib ‡600 mg. Dynamic contrast-enhanced magnetic resonance imaging demonstrated statistically significant decreases in parameters reflecting tumor vascularity and permeability after multiple doses in the 800-mg continuous q.d. and 400-mg b.i.d. dose cohorts. Conclusion: In patients with advanced/metastatic cancer, brivanib demonstrates promising antiangiogenic and antitumor activity and manageable toxicity at doses £800 mg orally q.d., the recommended phase II study dose. Key words: antiangiogenesis, brivanib, fibroblast growth factor, vascular endothelial growth factoren_US
dc.identifier.citationAnnals of Oncology 22: 1413–1419, 2011en_US
dc.identifier.otherdoi:10.1093/annonc/mdq599
dc.identifier.urihttp://hdl.handle.net/123456789/1122
dc.language.isoenen_US
dc.publisherAnnals of Oncologyen_US
dc.subjectStaff Publication - SoPen_US
dc.titlePhase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumorsen_US
dc.typeArticleen_US
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