Abstract
4549 Background: Tivozanib, a potent and selective oral small molecule tyrosine kinase inhibitor (TKI) of VEGFR-1, -2, and -3, has demonstrated antitumor activity in a phase II study in RCC. Temsirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is approved for treatment of advanced RCC. This phase Ib open-label study examined combination tivozanib and temsirolimus therapy in pts with advanced RCC to determine the safety and tolerability, maximum tolerated dose (MTD), and clinical activity. Methods: Pts with advanced RCC (with clear cell component) who had failed up to 1 prior VEGF-targeted therapy received daily oral tivozanib (3 wks on, 1 wk off = 1 cycle) and intravenous temsirolimus (once weekly). A standard 3+3 dose escalation design was used at four levels: 0.5 mg/d and 15 mg/wk; 1.0 mg/d and 15 mg/wk; 1.5 mg/d and 15 mg/wk; and 1.5 mg/day and 25 mg/wk of tivozanib and temsirolimus, respectively. Results: As of 1/24/11, 28 pts had been treated and accrual was closed. Demographic features were: 26 male/2 female; 89% Caucasian; median age 62 years (range, 43-71); Karnofsky Performance Status of 100/90/80 for 16, 7, and 4 pts, respectively (1 pt missing data). Twenty of 28 pts (71%) had received prior VEGF-targeted therapy. Median duration of treatment was 21.1 wks (range, 0.3-94.0). Treatment-related adverse events seen in ≥10% of pts were (number of pts with all grades/grade 3 toxicity): fatigue (20/4), decreased appetite (14/0), stomatitis (13/2), thrombocytopenia (10/4), diarrhea (16/2), nausea (13/1), constipation (10/1), and dypsnea (10/1). There were no grade 4 events. The MTD for the combination of tivozanib and temsirolimus was 1.5 mg/day and 25 mg/week, respectively. No dose limiting toxicities were observed. Clinical activity included: 28% PR, 64% SD and DCR (PR and SD>24weeks) of 48% in pts who had failed VEGF targeted therapies. Conclusions: Tivozanib is the first VEGFR TKI that can be combined with temsirolimus at full dose and schedule of both agents. The combination of tivozanib with temsirolimus was well tolerated and showed encouraging clinical activity in patients with advanced RCC.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
