Linifanib: Current status and future potential in cancer therapy

Expert Review of Anticancer Therapy

Volumn 15, Issue 6, 2015, Pages 677-687

  Aversa, Caterina ^a   Leone, Francesco ^a   Zucchini, Giorgia ^b   Serini, Guido ^a   Geuna, Elena ^b   Milani, Andrea ^b   Valdembri, Donatella ^a   Martinello, Rossella ^a   Montemurro, Filippo ^b  

^a UNIVERSITY OF TURIN   (Italy)

^b CANDIOLO CANCER INSTITUTE   (Italy)

Author keywords

ABT 869; angiogenesis; chemotherapy; Linifanib; PDGF; VEGF

Indexed keywords

ANTHRACYCLINE DERIVATIVE; AXITINIB; BEVACIZUMAB; CABOZANTINIB; CARBOPLATIN; CISPLATIN DERIVATIVE; CYTARABINE; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; IRINOTECAN; LINIFANIB; OXALIPLATIN; PACLITAXEL; PAZOPANIB; PLACEBO; PLATELET DERIVED GROWTH FACTOR RECEPTOR; RAPAMYCIN; REGORAFENIB; SORAFENIB; SUNITINIB; TAXANE DERIVATIVE; VANDETANIB; VASCULOTROPIN RECEPTOR; ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; CARBANILAMIDE DERIVATIVE; INDAZOLE DERIVATIVE; N-(4-(3-AMINO-1H-INDAZOL-4-YL)PHENYL)-N1-(2-FLUORO-5-METHYLPHENYL)UREA; PROTEIN KINASE INHIBITOR;

ALVEOLAR SOFT PART SARCOMA; ANEMIA; ANOREXIA; ANTINEOPLASTIC ACTIVITY; ASCITES; ASTHENIA; BRAIN DISEASE; BREAST CANCER; CANCER THERAPY; CHILD PUGH SCORE; COLON CARCINOMA; COLORECTAL CANCER; CONSTIPATION; DECREASED APPETITE; DIARRHEA; DRUG ABSORPTION; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FEBRILE NEUTROPENIA; HAND FOOT SYNDROME; HUMAN; HYPERBILIRUBINEMIA; HYPERTENSION; KIDNEY CARCINOMA; LEUKOPENIA; LIVER CELL CARCINOMA; MAXIMUM PLASMA CONCENTRATION; MULTIPLE CYCLE TREATMENT; MYALGIA; NAUSEA AND VOMITING; NEUTROPENIA; NON SMALL CELL LUNG CANCER; OVERALL SURVIVAL; PHARMACODYNAMICS; PHARMACOKINETICS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROCTALGIA; PROGRESSION FREE SURVIVAL; PROTEINURIA; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SKIN TOXICITY; SOLID TUMOR; STOMATITIS; THROMBOCYTOPENIA; UNSPECIFIED SIDE EFFECT; WEIGHT REDUCTION; XEROSTOMIA; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; PATHOLOGY; VASCULARIZATION;

ANGIOGENESIS INHIBITORS; ANTINEOPLASTIC AGENTS; HUMANS; INDAZOLES; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; PHENYLUREA COMPOUNDS; PROTEIN KINASE INHIBITORS;

EID: 84930451779     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/14737140.2015.1042369     Document Type: Review

References (85)

1. Folkman J, D'Amore PA. Blood vessel formation: what is its molecular basis Cell 1996;87:1153-5
2. Klagsbrun M, Moses MA. Molecular angiogenesis. Chem Biol 1999;6:217-24
3. Ferrara N, Gerber H-P, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669-76
4. Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002;29:15-18
5. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285: 1182-6
6. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005;307: 58-62
7. Folkman J, Klagsbrun M. Angiogenic factors. Science 1987;235:442-7
8. Thomas KA. Vascular endothelial growth factor, a potent and selective angiogenic agent. J Biol Chem 1996;271:603-6
9. Risau W. Mechanisms of angiogenesis. Nature 1997;386:671-4
10. Tammela T, Zarkada G, Wallgard E, et al. Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation. Nature 2008;454:656-60
11. Siekmann AF, Lawson ND. Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries. Nature 2007;445:781-4
12. Kowanetz M, Ferrara N. Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res 2006;12:5018-22
13. Wu FTH, Stefanini MO, Mac Gabhann F, et al. A systems biology perspective on sVEGFR1: its biological function, pathogenic role and therapeutic use. J Cell Mol Med 2010;14:528-52
14. Casanovas O, Hicklin DJ, Bergers G, et al. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 2005;8: 299-309
15. Mittal K, Ebos J, Rini B. Angiogenesis and the tumor microenvironment: vascular endothelial growth factor and beyond. Semin Oncol 2014;41:235-51
16. Carmeliet P. Angiogenesis in health and disease. Nat Med 2003;9:653-60
17. Song S, Ewald AJ, Stallcup W, et al. PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol 2005;7: 870-9
18. Saharinen P, Eklund L, Pulkki K, et al. VEGF and angiopoietin signaling in tumor angiogenesis and metastasis. Trends Mol Med 2011;17:347-62
19. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86: 353-64
20. Shojaei F. Anti-angiogenesis therapy in cancer: Current challenges and future perspectives. Cancer Lett 2012;320:130-7.
21. O'Farrell A-M, Abrams TJ, Yuen HA, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 2003;101:3597-605
22. Sleijfer S, Ray-Coquard I, Papai Z, et al. Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European Organisation for Research and Treatment of Cancer-soft tissue and bone sarcoma group (EORTC study 62043). J Clin Oncol 2009;27:3126-32
23. Kupsch P, Henning BF, Passarge K, et al. Results of a phase I trial of sorafenib (BAY 43-9006) in combination with oxaliplatin in patients with refractory solid tumors, including colorectal cancer. Clin Colorectal Cancer 2005;5:188-96
24. Langmuir PB, Yver A. Vandetanib for the treatment of thyroid cancer. Clin Pharmacol Ther 2012;91:71-80
25. Grüllich C. Cabozantinib: a MET, RET, and VEGFR2 tyrosine kinase inhibitor. Recent Results Cancer Res 2014;201:207-14
26. Ho TH, Jonasch E. Axitinib in the treatment of metastatic renal cell carcinoma. Future Oncol 2011;7:1247-53
27. Bergers G, Song S, Meyer-Morse N, et al. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 2003;111:1287-95
28. Erber R, Thurnher A, Katsen AD, et al. Combined inhibition of VEGF and PDGF signaling enforces tumor vessel regression by interfering with pericyte-mediated endothelial cell survival mechanisms. FASEB J 2004;18:338-40
29. Dai Y, Hartandi K, Ji Z, et al. Discovery of N-[4-[3-amino-1H-indazol-4-yl]phenyl]-N'-[2-fluoro-5-methylphenyl]urea (ABT-869), a 3-aminoindazole-based orally active multitargeted receptor tyrosine kinase inhibitor. J Med Chem 2007;50:1584-97
30. Albert DH, Tapang P, Magoc TJ, et al. Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther 2006;5: 995-1006.
31. Zhou J, Goh B-C, Albert DH, et al. ABT-869, a promising multi-targeted tyrosine kinase inhibitor: from bench to bedside. J Hematol Oncol 2009;2:33.
32. Shankar DB, Li J, Tapang et al. ABT-869, a multitargeted receptor tyrosine kinase inhibitor: inhibition of FLT3 phosphorylation and signaling in acute myeloid leukemia. Blood 2007;109: 3400-8
33. Hernandez-Davies JE, Zape JP, Landaw EM, et al. The multitargeted receptor tyrosine kinase inhibitor linifanib (ABT-869) induces apoptosis through an Akt and glycogen synthase kinase-dependent pathway. Mol Cancer Ther 2011;10:949-59
34. Jiang F, Albert DH, Luo Y, et al. ABT-869, a multitargeted receptor tyrosine kinase inhibitor, reduces tumor microvascularity and improves vascular wall integrity in preclinical tumor models. J Pharmacol Exp Ther 2011;338:134-42
35. Jasinghe VJ, Xie Z, Zhou J, et al. ABT-869, a multi-targeted tyrosine kinase inhibitor, in combination with rapamycin is effective for subcutaneous hepatocellular carcinoma xenograft. J Hepatol 2008;49:985-97
36. Donawho C, Hickson J, Wang Y-C, et al. The RTK inhibitor ABT-869, alone and in combination with paclitaxel and/or zoledronic acid, demonstrates significant reduction in the development of both osteoblastic [LuCap 23.1] and osteolytic [PC3-M-Luciferase] tumors intratibially. AACR Meet Abstr 2007;C204
37. Zhou J, Pan M, Xie Z, et al. Synergistic antileukemic effects between ABT-869 and chemotherapy involve downregulation of cell cycle-regulated genes and c-Mos-mediated MAPK pathway. Leukemia 2008;22:138-46
38. Wang ES, Yee K, Koh LP, et al. Phase 1 trial of linifanib (ABT-869) in patients with refractory or relapsed acute myeloid leukemia. Leuk Lymphoma 2012;53:1543-51
39. Wong C-I, Koh T-S, Soo R, et al. Phase I and biomarker study of ABT-869, a multiple receptor tyrosine kinase inhibitor, in patients with refractory solid malignancies. J Clin Oncol 2009;27: 4718-26.
40. Chiu Y-L, Carlson DM, Pradhan RS, et al. Exposure-response (safety) analysis to identify linifanib dose for a phase III study in patients with hepatocellular carcinoma. Clin Ther 2013;35:1770-7
41. Gupta N, Yan Z, LoRusso P, et al. Abstract B53: Assessment of the effect of food on the oral bioavailability and assessment of diurnal variation in the pharmacokinetics of linifanib. Mol Cancer Ther 2009;8:B53
42. Salem AH, Koenig D, Carlson D. Pooled Population pharmacokinetic analysis of Phase I, II and III studies of Linifanib in cancer patients. Clin Pharmacokinet 2014;53:347-59
43. Xiong H, Chiu Y-L, Ricker JL, et al. Results of a phase 1, randomized study evaluating the effects of food and diurnal variation on the pharmacokinetics of linifanib. Cancer Chemother Pharmacol 2014;74:55-61
44. A Phase 1 Study of ABT-869 in Subjects With Solid Tumors. Available from: https://clinicaltrials.gov/ct2/show/NCT00718380
45. Asahina H, Tamura Y, Nokihara H, et al. An open-label, phase 1 study evaluating safety, tolerability, and pharmacokinetics of linifanib (ABT-869) in Japanese patients with solid tumors. Cancer Chemother Pharmacol 2012;69:1477-86.
46. A Study of Linifanib (ABT-869) in Combination With Carboplatin/Paclitaxel in Japanese Subjects With Non-Small Cell Lung Cancer (NSCLC). Available from: https://clinicaltrials.gov/ct2/show/NCT01225302
47. Horinouchi H, Yamamoto N, Nokihara H, et al. A phase 1 study of linifanib in combination with carboplatin/paclitaxel as first-line treatment of Japanese patients with advanced or metastatic non-small cell lung cancer (NSCLC). Cancer Chemother Pharmacol 2014;74:37-43
48. Strumberg D, Clark JW, Awada A, et al. Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors. Oncologist 2007;12: 426-37
49. Faivre S, Bouattour M, Raymond E. Novel molecular therapies in hepatocellular carcinoma. Liver Int 2011;31(Suppl 1): 151-60
50. Phase 2 Study of ABT-869 in Combination With Paclitaxel Versus Paclitaxel Alone to Treat Metastatic Breast Cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT00645177
51. Rugo H, Lopez-Hernandez J, Gomez-Villanueva A, et al. ABT-869 in Combination with Paclitaxel (P) as First-Line Treatment in Patients (Pts) with Advanced Breast Cancer. Cancer Res 2009; 69(24 Suppl):5076
52. Takahashi Y, Kitadai Y, Bucana CD, et al. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. Cancer Res 1995;55: 3964-8
53. Phase 2 Study of ABT-869 in Combination With mFOLFOX6 Versus Bevacizumab in Combination With mFOLFOX6 to Treat Advanced Colorectal Cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT00707889
54. O'Neil BH, Cainap C, Van Cutsem E, et al. Randomized phase II open-label study of mFOLFOX6 in combination with linifanib or bevacizumab for metastatic colorectal cancer. Clin Colorectal Cancer 2014;13:156-63.e2
55. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-90
56. Cheng A-L, Kang Y-K, Chen Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009;10:25-34
57. Phase 2 Study of ABT-869 in Advanced Hepatocellular Carcinoma (HCC). Available from: https://clinicaltrials.gov/ct2/show/NCT00517920
58. Toh HC, Chen P-J, Carr BI, et al. Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma. Cancer 2013;119: 380-7.
59. Herbst RS, Onn A, Sandler A. Angiogenesis and Lung Cancer: Prognostic and Therapeutic Implications. J Clin Oncol 2005;23:3243-56
60. Study of ABT-869 in Subjects With Advanced Non-small Cell Lung Cancer (NSCLC). Available from: https://clinicaltrials.gov/ct2/show/NCT00517790
61. Tan E-H, Goss GD, Salgia R, et al. Phase 2 trial of Linifanib (ABT-869) in patients with advanced non-small cell lung cancer. J Thorac Oncol 2011;6:1418-25
62. Study of Carboplatin/Paclitaxel in Combination With ABT-869 in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC). Available from: https://clinicaltrials.gov/ct2/show/NCT00716534
63. Ramalingam SS, Shtivelband M, Soo RA, et al. Randomized Phase II study of carboplatin and paclitaxel with either linifanib or placebo for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 2015;33:433-41
64. Posadas EM, Limvorasak S, Sharma S, et al. Targeting angiogenesis in renal cell carcinoma. Expert Opin Pharmacother 2013;14:2221-36
65. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356:115-24
66. Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007;356:2271-81
67. Study of ABT-869 in Subjects With Advanced Renal Cell Carcinoma Who Have Previously Received Treatment With Sunitinib. Available from: https://clinicaltrials.gov/ct2/show/NCT00486538
68. Tannir NM, Wong Y-N, Kollmannsberger CK, et al. Phase 2 trial of linifanib (ABT-869) in patients with advanced renal cell cancer after sunitinib failure. Eur J Cancer 2011;47:2706-14
69. Efficacy and Tolerability of ABT-869 Versus Sorafenib in Advanced Hepatocellular Carcinoma (HCC). Available from: https://clinicaltrials.gov/ct2/show/NCT01009593
70. Cainap C, Qin S, Huang W-T, et al. Linifanib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: Results of a Randomized Phase III Trial. J Clin Oncol 2015;33:172-9.
71. Scagliotti G, Novello S, von Pawel J, et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol 2010;28:1835-42
72. Laurie SA, Solomon BJ, Seymour L, et al. Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29. Eur J Cancer 50:706-12
73. Scagliotti GV, Vynnychenko I, Park K, et al. International, randomized, placebo-controlled, double-blind phase III study of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous non-small-cell lung cancer: MONET1. J Clin Oncol 2012;30:2829-36
74. Cheng A-L, Kang Y-K, Lin D-Y, et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 2013;31:4067-75
75. Johnson PJ, Qin S, Park J-W, et al. Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL study. J Clin Oncol 2013;31:3517-24
76. Llovet JM, Hernandez-Gea V. Hepatocellular Carcinoma: Reasons for Phase III Failure and Novel Perspectives on Trial Design. Clin Cancer Res 2014;20(8): 2072-9
77. Wehland M, Bauer J, Magnusson ME, et al. Biomarkers for anti-angiogenic therapy in cancer. Int J Mol Sci 2013;14:9338-64.
78. 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 2004;64:7099-109
79. 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 [Internet]. Available from: http://clincancerres.aacrjournals.org [cited February 14, 2015]
80. Abrams TJ, Lee LB, Murray LJ, et al. SU11248 inhibits KIT and platelet-derived growth factor receptor b in preclinical models of human small cell lung cancer. Mol Cancer Ther 2003;2:471-8
81. Murray LJ, Abrams TJ, Long KR, et al. SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. Clin Exp Metastasis 2003;20:757-66
82. Kumar R, Knick VB, Rudolph SK, et al. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol Cancer Ther 2007;6:2012-21
83. Yakes FM, Chen J, Tan J, et al. Cabozantinib (XL184), a Novel MET and VEGFR2 Inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth [Internet]. Available from: http://mct.aacrjournals.org [cited February 14, 2015].
84. 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 2008;14:7272-83
85. Wedge SR, Ogilvie DJ, Dukes M, et al. ZD6474 Inhibits Vascular Endothelial Growth Factor Signaling, Angiogenesis, and Tumor Growth following Oral Administration. Cancer Res 2002;62: 4645-55