Tivozanib: Status of Development

Current Oncology Reports

Volumn 17, Issue 6, 2015, Pages 1-7

  Jamil, Muhammad Omer ^a   Hathaway, Amanda ^a   Mehta, Amitkumar ^a  

^a Heerskink School of Medicine   (United States)

Author keywords

Neuropilin 1; NRP 1; TIVO 1; Tivozanib; VEGF TKI

Indexed keywords

TIVOZANIB; VASCULOTROPIN RECEPTOR 2; ANTINEOPLASTIC AGENT; CARBANILAMIDE DERIVATIVE; PROTEIN KINASE INHIBITOR; QUINOLINE DERIVATIVE; VASCULOTROPIN RECEPTOR;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; ATAXIA; BLOOD VESSEL PERMEABILITY; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER INHIBITION; COLORECTAL CANCER; DOWN REGULATION; DRUG MECHANISM; DYSPHONIA; GROWTH INHIBITION; HUMAN; HYPERTENSION; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN PHOSPHORYLATION; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; ANTAGONISTS AND INHIBITORS; MOLECULARLY TARGETED THERAPY; NEOPLASMS; PROCEDURES;

ANTINEOPLASTIC AGENTS; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS; PHENYLUREA COMPOUNDS; PROTEIN KINASE INHIBITORS; QUINOLINES; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR;

EID: 84928397018     PISSN: 15233790     EISSN: 15346269     Source Type: Journal    
DOI: 10.1007/s11912-015-0451-3     Document Type: Review

References (32)

1. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285(21):1182–6. This article describes role of angiogenesis in tumor growth and metastasis. This article expands the understanding of tumor environment and ecosystem of tumor cells and cell producing blood vessels.
2. Muthukkaruppan VR, Kubai L, Auerbach R. Tumor-induced neovascularization in the mouse eye. J Natl Cancer Inst. 1982;69(3):699–708.
3. Holmgren L, O'Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med. 1995;1(2):149–53.
4. Parangi S, O'Reilly M, Christofori G, et al. Antiangiogenic therapy of transgenic mice impairs de novo tumor growth. Proc Natl Acad Sci U S A. 1996;93(5):2002–7.
5. Nishida N, Yano H, Nishida T, Kamura T, Kojiro M. Angiogenesis in cancer. Vasc Health Risk Manag. 2006;2(3):213–9.
6. Morabito A, Maio ED, Maio MD, Normanno N, Perrone F. Tyrosine kinase inhibitors of vascular endothelial growth factor receptors in clinical trials: current status and future directions. 2006.
7. Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature. 1993;362(6423):841–4.
8. Development of second-generation VEGFR tyrosine kinase inhibitors: cur. 2015.
9. Mehta A, Sonpavde G, Escudier B. Tivozanib for the treatment of renal cell carcinoma: results and implications of the TIVO-1 trial. Future Oncol. 2014;10(11):1819–26. This article describes one and only phase III trial of Tivozanib in renal cell cancer. The article also describes preclinical and early phase clinical trials of tivozanib in RCC.
10. Nakamura K, Taguchi E, Miura T et al. KRN951, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, has antitumor activities and affects functional vascular properties. In: Cancer Res. (United States, 2006) 9134-9142.
11. Escudier B, Gore M. Axitinib for the management of metastatic renal cell carcinoma. In: Drugs R D. (New Zealand, 2011) 113-126.
12. Gross-Goupil M, François L, Quivy A, Ravaud A. Axitinib: a review of its safety and efficacy in the treatment of adults with advanced renal cell carcinoma. Clin Med Insights Oncol. 2013;7:269–77.
13. Kumar R, Crouthamel MC, Rominger DH et al. Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors. In: Br J Cancer. (England, 2009) 1717-1723.
14. Eskens FA, de Jonge MJ, Bhargava P, et al. Biologic and clinical activity of tivozanib (AV-951, KRN-951), a selective inhibitor of VEGF receptor-1, -2, and -3 tyrosine kinases, in a 4-week-on, 2-week-off schedule in patients with advanced solid tumors. Clin Cancer Res. 2011;17(22):7156–63.
15. Fishman MN, Srinivas S, Hauke RJ, et al. Phase Ib study of tivozanib (AV-951) in combination with temsirolimus in patients with renal cell carcinoma. Eur J Cancer. 2013;49(13):2841–50.
16. Nosov DA, Esteves B, Lipatov ON, et al. Antitumor activity and safety of tivozanib (AV-951) in a phase II randomized discontinuation trial in patients with renal cell carcinoma. J Clin Oncol. 2012;30(14):1678–85.
17. Motzer RJ, Nosov D, Eisen T, et al. Tivozanib versus sorafenib as initial targeted therapy for patients with metastatic renal cell carcinoma: results from a phase III trial. J Clin Oncol. 2013;31(30):3791–9. This is actual publication of TIVO-1 trial. This paper describes details of the trial and out comes.
18. Mayer EL, Scheulen ME, Beckman J, et al. A phase I dose-escalation study of the VEGFR inhibitor tivozanib hydrochloride with weekly paclitaxel in metastatic breast cancer. Breast Cancer Res Treat. 2013;140(2):331–9.
19. Oldenhuis CN, Loos WJ, Esteves B, et al. A phase Ib study of the VEGF receptor tyrosine kinase inhibitor tivozanib and modified FOLFOX-6 in patients with advanced gastrointestinal malignancies. Clin Colorectal Cancer. 2015;14(1):18–24. e11.
20. Benson A, Bridgewater J, Kiss I, et al. 533PBATON-CRC: a phase 2 randomized trial comparing tivozanib (TIVO)+ MFOLFOX6 with bevacizumab (BEV)+ MFOLFOX6 in stage IV metastatic colorectal cancer (MCRC). Ann Oncol. 2014;25 suppl 4:iv182.
21. Wolpin BM, Ng K, Zhu AX et al. Multicenter phase Ib/II study of everolimus (RAD001) and tivozanib (AV-951) in patients with refractory, metastatic colorectal cancer. 2012.
22. Wolpin BM, Ng K, Zhu AX et al. Multicenter phase II study of tivozanib (AV-951) and everolimus (RAD001) for patients with refractory, metastatic colorectal cancer. In: Oncologist. (United States, 2013) 377-378.
23. Pal SK, Bergerot PG, Figlin RA. Tivozanib: current status and future directions in the treatment of solid tumors. Expert Opin Investig Drugs. 2012;21(12):1851–9.
24. Hepgur M, Sadeghi S, Dorff TB, Quinn DI. Tivozanib in the treatment of renal cell carcinoma. In: Biologics. 2013 139-148.
25. Cella DIC, Skaltsa K, Casamayor M, Strahs AL, Esteves B et al. Treatment benefit of tivozanib hydrochloride versus sorafenib on health-related quality of life (HRQoL) among patients (pts) with advanced/metastatic renal cell carcinoma (mRCC): TIVO-1 study results. Ed.(Eds) (ASCO Meeting Abstracts. 2013;31:355.)
26. Hutson TE ND, Harza M, Esteves B, Strahs AL, Berkenblit A et al. Rates of dose adjustment in patients treated with tivozanib versus sorafenib in the phase III TIVO-1 study. Ed.(Eds) (ASCO Meeting Abstracts. 2013;31:4564.)
27. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM351322.pdf.Ed.(Eds).
28. A subject treatment preference study of tivozanib hydrochloride versus sunitinib in subjects with metastatic renal cell carcinoma - full text view - clinicaltrials.gov. Ed.^(Eds). 2015.
29. Tivozanib hydrochloride in combination with paclitaxel versus placebo with paclitaxel in patients with locally recurrent or metastatic triple negative breast cancer - full text view - clinicaltrials.gov.Ed.^(Eds). 2015.
30. A rollover protocol to allow continued access to tivozanib (AV 951) for subjects enrolled in other tivozanib protocols - full text view - clinicaltrials.gov. Ed.^(Eds).2015.
31. A trial of tivozanib(AV-951)in combination with capecitabine(Xeloda®) in subjects with advanced solid tumors - full text view - clinicaltrials.gov. Ed.^(Eds). 2015.
32. Benson AB KA, Van Sant C et al. Neuropilin-1 as a potential biomarker of progression-free survival benefit for tivozanib plus mFOLFOX6 versus bevacizumab plus mFOLFOX6 in metastatic colorectal cancer: post-hoc biomarker analysis of BATON-CRC phase II trial. Ed.^(Eds)(Poster presented at the AACR Angiogeneis Meeting; March 6, 2015, Orlando, FL. Abstract 24). This abstract was recently published and is a proof of concept that NRP-1 (neuropilin-1) is a biomarker for Tivozanib activity.