Pazopanib: Therapeutic developments

Expert Opinion on Pharmacotherapy

Volumn 10, Issue 18, 2009, Pages 3091-3102

  Limvorasak, Suwicha ^a   Posadas, Edwin M ^a  

^a UNIVERSITY OF CHICAGO   (United States)

Author keywords

Ovarian cancer; Pazopanib; Renal cell carcinoma; Soft tissue sarcoma; Tyrosine kinase inhibitor; VEGFR

Indexed keywords

CAPECITABINE; CETUXIMAB; DOCETAXEL; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; KETOCONAZOLE; LAPATINIB; OXALIPLATIN; PACLITAXEL; PAZOPANIB; PEMETREXED; PLACEBO; THALIDOMIDE; UNCLASSIFIED DRUG; VOTRIENT;

ADVANCED CANCER; ANGIOGENESIS; ANOREXIA; AREA UNDER THE CURVE; ASTHENIA; BONE MARROW SUPPRESSION; BREAST CANCER; BREAST CARCINOMA; CELL PROLIFERATION; CLINICAL TRIAL; COLORECTAL CANCER; CONFUSION; DEPIGMENTATION; DIARRHEA; DISEASE COURSE; DRUG ABSORPTION; DRUG ACTIVITY; DRUG APPROVAL; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; FOOD AND DRUG ADMINISTRATION; GLIOMA; HAIR DISEASE; HUMAN; HYPERTENSION; HYPOPIGMENTATION; IC 50; INVASIVE CARCINOMA; KIDNEY CARCINOMA; LABORATORY TEST; LEIOMYOSARCOMA; LIVER CELL CARCINOMA; LUNG NON SMALL CELL CANCER; MAXIMUM PLASMA CONCENTRATION; MELANOMA; METASTASIS; MULTIPLE MYELOMA; NASOPHARYNX CANCER; NAUSEA; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OPTIMAL DRUG DOSE; OVARY CANCER; PERITONEUM CANCER; PLEURA MESOTHELIOMA; PROSTATE CANCER; PROTEINURIA; QUALITY OF LIFE; RECURRENT CANCER; REVIEW; SIDE EFFECT; SOFT TISSUE SARCOMA; SOLID TUMOR; SYNOVIAL SARCOMA; THROMBOCYTOPENIA; UNSPECIFIED SIDE EFFECT; UROGENITAL TRACT CANCER; UTERINE CERVIX CANCER; VOMITING;

ANTINEOPLASTIC AGENTS; CARCINOMA, RENAL CELL; CLINICAL TRIALS AS TOPIC; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; HUMANS; KIDNEY NEOPLASMS; NEOPLASMS; PROTEIN-TYROSINE KINASES; PYRIMIDINES; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; SULFONAMIDES; VASCULAR ENDOTHELIAL GROWTH FACTORS;

EID: 71449106319     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656560903436493     Document Type: Review

References (76)

1. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669-676
2. Duda DG, Batchelor TT, Willett CG, et al. VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects. Trends Mol Med 2007;13:223-230
3. O'Reilly MS. Antiangiogenesis and vascular endothelial growth factor/vascular endothelial growth factor receptor targeting as part of a combined-modality approach to the treatment of cancer. Int J Radiat Oncol Biol Phys 2007;69:S64-6
4. Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2000;103:211-225
5. Presta LG, Chen H, O'Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997;57:4593-4599
6. Borgstrom P, Hillan KJ, Sriramarao P, et al. Complete inhibition of angiogenesis and growth of microtumors by anti-vascular endothelial growth factor neutralizing antibody: novel concepts of angiostatic therapy from intravital videomicroscopy. Cancer Res 1996;56:4032-4039
7. Morabito A, De Maio E, Di Maio M, et al. Tyrosine kinase inhibitors of vascular endothelial growth factor receptors in clinical trials: current status and future directions. Oncologist 2006;11:753-764
8. 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;6:2012-2021
9. Hartman GD, Fraley ME, Bilodeau MT. Kinase insert domain-containing receptor kinase inhibitors as anti-angiogenic agents. Expert Opin Investig Drugs 2002;11:737-745
10. Sloan B, Scheinfeld NS. Pazopanib, a VEGF receptor tyrosine kinase inhibitor for cancer therapy. Curr Opin Investig Drugs 2008;9:1324-1335
11. Cao Y, Liu Q. Therapeutic targets of multiple angiogenic factors for the treatment of cancer and metastasis. Adv Cancer Res 2007;97:203-224
12. Cao Y, Zhong W. Tumor-derived lymphangiogenic factors and lymphatic metastasis. Biomed Pharmacother 2007;61:534-539
13. Harris PA, Boloor A, Cheung M, et al. Discovery of 5-[[4-[(2,3-dimethyl- 2H-indazol-6-yl) methylamino]-2-pyrimidinyl]amino]-2-m ethyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. J Med Chem 2008;51:4632-4640
14. Liu DQ, Chen TK, McGuire MA, et al. Analytical control of genotoxic impurities in the pazopanib hydrochloride manufacturing process. J Pharm Biomed Anal 2009;50:144-150
15. Sorbera L, Bolos J, Serradell N. Pazopanib hydrochloride. Oncolytic, agiogenesis inhibitor, VEGFR-2 tyrosine kinase inhibitor. Drugs Future 2006;31:585-589
16. Sonpavde G, Hutson TE, Sternberg CN. Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma. Expert Opin Investig Drugs 2008;17:253-261
17. Dev IK, Dornsife RE, Hopper TM, et al. Antitumour efficacy of VEGFR2 tyrosine kinase inhibitor correlates with expression of VEGF and its receptor VEGFR2 in tumour models. Br J Cancer 2004;91:1391-1398
18. Suttle AB, Hurwitz H, Dowlati A, et al. Pharmacokinetics (PK) and tolerability og GW786034, a VEGFR tyrosine kinase inhibitor, after daily oral administration to patients with solid tumors. J Clin Oncol 2004;22(Suppl): Abstract 3054
19. Suttle B, Jones S, Dowlati A, et al. Phase I study of the safety and pharmacokinetics (PK) of paclitaxel or paclitaxel with carboplatin administered in combination with pazopanib (GW786034). J Clin Oncol 2007;25(Suppl):Abstract 14118
20. Podar K, Tonon G, Sattler M, et al. The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. Proc Natl Acad Sci USA 2006;103:19478-19483
21. Hurwitz H, Dowlati A, Savage S, et al. Safety, tolerability and pharmacokinetics of oral administration of GW786034 in patients with solid tumors. J Clin Oncol 2005;23(Suppl):Abstract 3012
22. Hurwitz HI, Dowlati A, Saini S, et al. Phase I trial of pazopanib in patients with advanced cancer. Clin Cancer Res 2009;15:4220-4227
23. Yau CC, Chen PJ, Curtis CM, et al. A phase I study of pazopanib in patients with advanced hepatocellular carcinoma. J Clin Oncol 2009;27(Suppl):Abstract 3561
24. Okita NT, Yamada Y, Takahari D, et al. Vascular endothelial growth factor receptor expression as a prognostic marker for survival in colorectal cancer. Jpn J Clin Oncol 2009;39(9):595-600
25. Brady J, Middleton M, Midgley RS, et al. A phase I study of pazopanib in combination with FOLFOX6 or capeOx in subjects with colorectal cancer. J Clin Oncol 2009;27(Suppl):Abstract 4133
26. Pander J, Gelderblom H, Guchelaar HJ. Pharmacogenetics of EGFR and VEGF inhibition. Drug Discov Today 2007;12:1054-1060
27. Pennell NA, Lynch TJ Jr. Combined inhibition of the VEGFR and EGFR signaling pathways in the treatment of NSCLC. Oncologist 2009;14:399-411
28. Tabernero J. The role of VEGF and EGFR inhibition: implications for combining anti-VEGF and anti-EGFR agents. Mol Cancer Res 2007;5:203-220
29. Dejonge M, Savage S, Verweij J, et al. A phase I, open-label study of the safety and pharmacokinetics (PK) of pazopanib (P) and lapatinib (L) administered concurrently. J Clin Oncol 2006;24(Suppl):Abstract 3088
30. Frentzas SN, Groves MD, Barriuso J, et al. Pazopanib and lapatinib in patients with relapsed malignant glioma: results of a phase I/II study. J Clin Oncol 2009;27(Suppl):Abstract 2040
31. Konecny GE, Meng YG, Untch M, et al. Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res 2004;10:1706-1716
32. Taylor SK, Chia S, Dent S, et al. A phase II study of GW786034 (pazopanib) in patients with recurrent or metastatic invasive breast carcinoma: results after completion of stage I: a trial of the Princess Margaret hospital phase II consortium. J Clin Oncol 2009;27(Suppl):Abstract 1133
33. Slamon DJ, Gomez HL, Kabbinavar FF. Randomized study of pazopanib + lapatinib vs. lapatinib alone in patients with HER2-positive advanced or metastatic breast cancer. J Clin Oncol 2008;26(Suppl):Abstract 1016
34. Stefanou D, Goussia AC, Arkoumani E, et al. Expression of vascular endothelial growth factor and the adhesion molecule E-cadherin in non-small cell lung cancer. Anticancer Res 2003;23:4715-4720
35. Ludovini V, Gregorc V, Pistola L, et al. Vascular endothelial growth factor, p53, Rb, Bcl-2 expression and response to chemotherapy in advanced non-small cell lung cancer. Lung Cancer 2004;46:77-85
36. Tomita M, Matsuzaki Y, Shimizu T, et al. Vascular endothelial growth factor expression in pN2 non-small cell lung cancer: lack of prognostic value. Respirology 2005;10:31-35
37. Kajita T, Ohta Y, Kimura K, et al. The expression of vascular endothelial growth factor C and its receptors in non-small cell lung cancer. Br J Cancer 2001;85:255-260 (Pubitemid 32695748)
38. Mineo TC, Ambrogi V, Baldi A, et al. Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB-IIA non-small cell lung cancer. J Clin Pathol 2004;57:591-597
39. Altorki N, Guarino M, Lee P, et al. Preoperative treatment with pazopanib (GW786034), a multikinase angiogenesis inhibitor in early-stage non-small cell lung cancer (NSCLC): a proof-of-concept phase II study. J Clin Oncol 2008;26(Suppl):Abstract 7557
40. 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;27:3126-3132
41. Sleijfer S, Papai Z, Le Cesne A. Phase II study of pazopanib (GW786034) in patients with relapsed or refractory soft tissue sarcoma (STS): EORTC 62043. J Clin Oncol 2007;25(Suppl):Abstract 10031
42. Posadas EM, Dahut WL. Angiogenesis and angiogenesis inhibitors: applications in adenocarcinoma of the prostate. In: Ross JS, Foster CS, editors, Molecular oncology of prostate cancer. 1st edition. Jones and Bartlett, Liverpool, England; 2006
43. Chi KN, Ellard SL, Hotte SJ, et al. A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer. Ann Oncol 2008;19:746-751
44. Dahut WL, Scripture C, Posadas E, et al. A phase II clinical trial of sorafenib in androgen-independent prostate cancer. Clin Cancer Res 2008;14:209-214
45. Dror Michaelson M, Regan MM, Oh WK, et al. Phase II study of sunitinib in men with advanced prostate cancer. Ann Oncol 2009;20:913-2046.
46. Steinbild S, Mross K, Frost A, et al. A clinical phase II study with sorafenib in patients with progressive hormone-refractory prostate cancer: a study of the CESAR Central European Society for Anticancer Drug Research-EWIV. Br J Cancer 2007;97:1480-1485
47. Cox MC, Dahut WL, Figg WD. The use of thalidomide in androgen-independent prostate cancer. Urol Oncol 2006;24:246-249
48. Friedlander M, Hancock KC, Benigno B, et al. Pazopanib (GW786034) is active in women with advanced epithelial ovarian, fallopian tube and peritoneal cancers: initial results of a phase II study. J Clin Oncol 2007;25(Suppl): Abstract 5561
49. Hutson TE, Bukowski RM. A phase II study of GW786034 using a randomized discontinuation design in patients with locally recurrent or metastatic clear-cell renal cell carcinoma. Clin Genitourin Cancer 2006;4:296-298
50. Vakkalanka BK, Rini BI. Targeted therapy in renal cell carcinoma. Curr Opin Urol 2008;18:481-487
51. Dietrich J, Norden AD, Wen PY. Emerging antiangiogenic treatments for gliomas - efficacy and safety issues. Curr Opin Neurol 2008;21:736-744
52. Norden AD, Drappatz J, Wen PY. Antiangiogenic therapy in malignant gliomas. Curr Opin Oncol 2008;20:652-661
53. Davids M, Charlton A, Ng SS, et al. Response to a novel multitargeted tyrosine kinase inhibitor pazopanib in metastatic merkel cell carcinoma. J Clin Oncol 2009;27:97-100
54. Chappelow AV, Kaiser PK. Neovascular age-related macular degeneration: potential therapies. Drugs 2008;68:1029-1036
55. Takahashi K, Saishin Y, King AG, et al. Suppression and regression of choroidal neovascularization by the multitargeted kinase inhibitor pazopanib. Arch Ophthalmol 2009;127:494-499
56. Podar K, Tonon G, Abtahi D, et al. In vitro and in vivo activity of the VEGF receptor inhibitor pazopanib (GW786034) in multiple myeloma: therapeutic implications. Proc Am Assoc Cancer Res 2006;47:Abstract 5658
57. Podar K, Catley LP, Tai YT, et al. GW654652, the pan-inhibitor of VEGF receptors, blocks the growth and migration of multiple myeloma cells in the bone marrow microenvironment. Blood 2004;103:3474-3479
58. Prince HM, Honemann D, Spencer A, et al. Vascular endothelial growth factor inhibition is not an effective therapeutic strategy for relapsed or refractory multiple myeloma: a phase 2 study of pazopanib (GW786034). Blood 2009;113:4819-4820
59. Hideshima T, Chauhan D, Podar K, et al. Novel therapies targeting the myeloma cell and its bone marrow microenvironment. Semin Oncol 2001;28:607-612
60. Bible KC, Smallridge RC, Maples WJ, et al. Phase II trial of pazopanib in progressive, metastatic, iodine-insensitive differentiated thyroid cancers. J Clin Oncol 2009;27(Suppl):Abstract 3521
61. Sternberg CN, Szczylik C, Lee E, et al. A randomized, double-blind phase III study of pazopanib in treatment naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC). J Clin Oncol 2009;27(Suppl):Abstract 5021
62. Bhargava P. VEGF kinase inhibitors: how do they cause hypertension? Am J Physiol Regul Integr Comp Physiol 2009;297:R1-5
63. Facemire CS, Nixon AB, Griffiths R, et al. Vascular endothelial growth factor receptor 2 controls blood pressure by regulating nitric oxide synthase expression. Hypertension 2009;54:652-658
64. Rosenbaum SE, Wu S, Newman MA, et al. Dermatological reactions to the multitargeted tyrosine kinase inhibitor sunitinib. Support Care Cancer 2008;16:557-566
65. Azad NS, Aragon-Ching JB, Dahut WL, et al. Hand-foot skin reaction increases with cumulative sorafenib dose and with combination anti-vascular endothelial growth factor therapy. Clin Cancer Res 2009;15:1411-1416
66. Robert C, Spatz A, Faivre S, et al. Tyrosine kinase inhibition and grey hair. Lancet 2003;361:1056
67. Routhouska S, Gilliam AC, Mirmirani P. Hair depigmentation during chemotherapy with a class III/V receptor tyrosine kinase inhibitor. Arch Dermatol 2006;142:1477-1479
68. Widakowich C, de Castro G Jr, De Azambuja E, et al. Review: side effects of approved molecular targeted therapies in solid cancers. Oncologist 2007;12:1443-1455
69. Robert C, Soria JC, Spatz A, et al. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol 2005;6:491-500
70. Botchkareva NV, Khlgatian M, Longley BJ, et al. SCF/c-kit signaling is required for cyclic regeneration of the hair pigmentation unit. FASEB J 2001;15:645-658
71. Ryan CW, Von Mehren M, Rankin CJ, et al. Phase II intergroup study of sorafenib (S) in advanced soft tissue sarcomas (STS): SWOG 0505. J Clin Oncol 2008;26(Suppl):Abstract 10532
72. Keohan ML, Morgan JA, D'Adamo DR, et al. Continuous daily dosing (CDD) of sunitinib (SU) in patients with metastatic soft tissue sarcomas (STS) other than GIST: results of a phase II trial. J Clin Oncol 2008;26(Suppl):Abstract 10533
73. Matei D, Sill MW, Degeest K, Bristow RE. Phase II trial of sorafenib in persistent or recurrent epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC): a gynecologic oncology group (GOG) study. J Clin Oncol 2008;26(Suppl):Abstract 5537
74. Biagi JJ, Oza AM, Grimshaw R, et al. A phase II study of sunitinib (SU11248) in patients (pts) with recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma - NCIC CTG IND 185. J Clin Oncol 2008;26(Suppl):Abstract 5522
75. Deprimo SE, Friece C, Smeraglia J, et al. Effect of treatment with sunitinib malate, a multitargeted tyrosine kinase inhibitor, on circulating plasma levels of VEGF, soluble VEGF receptors 2 and 3, and soluble KIT patients with metastatic breast cancer. ASCO Annual Meeting Proceedings Part 1. J Clin Oncol 2006;24(18S):57876.
76. Aspitia AM, Morton RF, Hillman DW, et al. Phase II trial of sorafenib in patients with metastatic breast cancer previously exposed to anthracycline or taxanes: North central cancer treatment group and Mayo Clinic trial N0336. J Clin Oncol 2009;27:11-15