Structure, development, preclinical and clinical efficacy of tivozanib (KRN-951, AV-951)

Future Oncology

Volumn 9, Issue 1, 2013, Pages 13-20

  Haberkorn, Brigitte C M ^a   Eskens, Ferry A L M ^a  

^a ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

angiogenesis; renal cell cancer; tivozanib; VEGFR tyrosine kinase inhibitor

Indexed keywords

ALPHA INTERFERON; AXITINIB; EVEROLIMUS; FLUOROURACIL; FOLINIC ACID; OXALIPLATIN; PAZOPANIB; SORAFENIB; SUNITINIB; TIVOZANIB;

ANOREXIA; ATAXIA; CONTINUOUS INFUSION; DEHYDRATION; DIARRHEA; DRUG DOSE REDUCTION; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEVER; GASTROINTESTINAL STROMAL TUMOR; HAIR DISCOLORATION; HAND FOOT SYNDROME; HEADACHE; HOARSENESS; HUMAN; HYPERGLYCEMIA; HYPERTENSION; HYPERTRANSAMINASEMIA; HYPOPHOSPHATEMIA; KIDNEY CARCINOMA; LIVER DYSFUNCTION; LUNG EMBOLISM; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; NONHUMAN; PRIORITY JOURNAL; PROTEINURIA; REVIEW; SEIZURE; VERTIGO; VOMITING;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, RENAL CELL; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; DRUG EVALUATION, PRECLINICAL; HUMANS; KIDNEY NEOPLASMS; PHENYLUREA COMPOUNDS; QUINOLINES;

EID: 84871430607     PISSN: 14796694     EISSN: 17448301     Source Type: Journal    
DOI: 10.2217/fon.12.167     Document Type: Review

References (39)

1. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat. Med. 9(6), 669-676 (2003). (Pubitemid 36749215)
2. Harris AL. Hypoxia Y a key regulatory factor in tumour growth. Nat. Rev. Cancer 2(1), 38-47 (2002). (Pubitemid 37328806)
3. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 13(1), 9-22 (1999). (Pubitemid 29038270)
4. Zhan P, Wang J, Lv XJ et al. Prognostic value of vascular endothelial growth factor expression in patients with lung cancer: A systematic review with meta-analysis. J. Thorac. Oncol. 4(9), 1094-1103 (2009).
5. Schoenleber SJ, Kurtz DM, Talwalkar JA, Roberts LR, Gores GJ. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: Systematic review and meta-analysis. Br. J. Cancer 100(9), 1385-1392 (2009).
6. Shih T, Lindley C. Bevacizumab: An angiogenesis inhibitor for the treatment of solid malignancies. Clin. Ther. 28(11), 1779-1802 (2006). (Pubitemid 46038527)
7. Spratlin JL, Mulder KE, Mackey Jr. Ramucirumab (IMC-1121B): A novel attack on angiogenesis. Future Oncol. 6(7), 1085-1094 (2010).
8. Wells SA Jr, Robinson BG, Gagel RF et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: A randomized, double-blind Phase III trial. J. Clin. Oncol. 30(2), 134-141 (2012).
9. 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. Cancer Res. 66, 9134-9142 (2006). (Pubitemid 44521133)
10. Taguchi E, Nakamura K, Miura T, Shibuya M, Isoe T. Anti-tumor activity and tumor vessel normalization by the vascular endothelial growth factor receptor tyrosine kinase inhibitor KRN951 in a rat peritoneal disseminated tumor model. Cancer Sci. 99, 623-630 (2008). (Pubitemid 351228583)
11. Wilhelm SM, Carter C, Tang L et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/ MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64(19), 7099-7109 (2004). (Pubitemid 39331023)
12. Mendel DB, Laird AD, Xin X et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: Determination of a pharmacokinetic/pharmacodynamic relationship. Clin. Cancer Res. 9, 327-337 (2003). (Pubitemid 36109749)
13. Patyna S, Laird AD, Mendel DB et al. SU14813: A novel multiple receptor tyrosine kinase inhibitor with potent antiangiogenic and antitumor activity. Mol. Cancer Ther. 5(7), 1774-1782 (2006). (Pubitemid 44323245)
14. Kumar R, Knick VB, Rudolph SK et al. PharmacokineticYpharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol. Cancer Ther. 6, 2012-2021 (2007). (Pubitemid 47052491)
15. Hu-Lowe DD, Zou HY, Grazzini ML et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin. Cancer Res. 14(22), 7272-7283 (2008).
16. Wood JM, Bold G, Buchdunger E et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res. 60(8), 2178-2189 (2000). (Pubitemid 30225181)
17. Wedge SR, Ogilvie DJ, Dukes M et al. ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration. Cancer Res. 62(16), 4645-4655 (2002).
18. Wedge SR, Kendrew J, Hennequin LF et al. AZD2171: A highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 65, 4389-4400 (2005). (Pubitemid 40775678)
19. Polverino A, Coxon A, Starnes C. AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts. Cancer Res. 66(17), 8715-8721 (2006). (Pubitemid 44449188)
20. Traxler P, Allegrini PR, Brandt R et al. AEE788: A dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res. 64, 4931-4941 (2004). (Pubitemid 38924540)
21. Eskens FALM, 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. 17, 7156-7163 (2011).
22. 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. 30, 1678-1685 (2012).
23. Motzer RJ, Nosov D, Eisen T et al. Tivozanib versus sorafenib as initial targeted therapy for patients with advanced renal cell carcinoma: Results from a Phase 3 randomized, open-label, multicenter trial. J. Clin. Oncol. 30, 4501 (Abstract) (2012).
24. Motzer RJ, Hutson TE, Tomczak P et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 27(22), 3584-3590 (2009).
25. Sternberg CN, Davis ID, Mardiak J et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: Results of a randomized Phase III trial. J. Clin. Oncol. 28(6), 1061-1068 (2010).
26. Rini BI, Escudier B, Tomczak P et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): A randomised Phase 3 trial. Lancet 378(9807), 1931-1939 (2011).
27. Escudier B, Eisen T, Stadler WM et al. Sorafenib for treatment of renal cell carcinoma: Final efficacy and safety results of the Phase III treatment approaches in renal cancer global evaluation trial. J. Clin. Oncol. 27(20), 3312-3318 (2009).
28. Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 356(2), 125-134 (2007). (Pubitemid 46089673)
29. Ryan CW, Goldman BH, Lara PN Jr et al. Sorafenib with interferon alfa-2b as first-line treatment of advanced renal cell carcinoma: A Phase II study of the Southwest Oncology Group. J. Clin. Oncol. 25(22), 3296-3301 (2007). (Pubitemid 47325615)
30. Azad NS, Posadas EM, Kwitkowski VE et al. Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J. Clin. Oncol. 26(22), 3709-3714 (2008).
31. Patel PH, Senico PL, Curiel RE, Motzer RJ. Phase I study combining treatment with temsirolimus and sunitinib malate in patients with advanced renal cell carcinoma. Clin. Genitourin. Cancer 7(1), 24-27 (2009).
32. Negrier S, Gravis G, Perol D et al. Temsirolimus and bevacizumab, or sunitinib, or interferon alfa and bevacizumab for patients with advanced renal cell carcinoma (TORAVA): A randomised Phase 2 trial. Lancet Oncol. 12(7), 673-680 (2011).
33. Miller K, Wang M, Gralow J et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N. Engl. J. Med. 357(26), 2666-2676 (2007).
34. Feldman DR, Baum MS, Ginsberg MS et al. Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 27(9), 1432-1439 (2009).
35. Molina AM, Feldman DR, Voss MH et al. Phase 1 trial of everolimus plus sunitinib in patients with metastatic renal cell carcinoma. Cancer 118(7), 1868-1876 (2012).
36. Kabbinavar FF, Srinivas S, Hauke RJ et al. A Phase I trial of combined tivozanib (AV-951) and temsirolimus therapy in patients with renal cell carcinoma (RCC).J. Clin. Oncol. 29, 330 (Abstract) (2011).
37. Mayer EL, Scheulen ME, Beckman J et al. Combination of tivozanib (AV-951) with weekly paclitaxel for metastatic breast cancer: Results of a Phase I study. J. Clin. Oncol. 29, 1092 (Abstract) (2011).
38. 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. J. Clin. Oncol. 30, 560 (Abstract) (2012).
39. Eskens F, Oldenhuis CN, Bhargava P et al. A Phase Ib, open-label, dose-escalation study of tivozanib and FOLFOX6 in patients (pts) with advanced gastrointestinal (GI) tumors. J. Clin. Oncol. 29, 549 (Abstract) (2011).