The effects of liver impairment on the pharmacokinetics of brivanib, a dual inhibitor of fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases

Cancer Chemotherapy and Pharmacology

Volumn 72, Issue 1, 2013, Pages 53-64

  El Khoueiry, Anthony ^a   Posey, James A ^b   Castillo Ferrando, Juan Ramón ^c   Krishnamurthi, Smitha S ^d   Syed, Shariq ^e   Kollia, Georgia ^f   Walters, Ian ^f   Fischer, Bruce S ^f   Masson, Eric ^f  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^c HOSPITAL UNIVERSITARIO VIRGEN DEL ROCÍO   (Spain)

^d UNIVERSITY HOSPITALS OF CLEVELAND   (United States)

^e Bristol Myers Squibb ^*

^f BRISTOL MYERS SQUIBB   (United States)

Author keywords

Brivanib; Hepatocellular carcinoma; Liver impairment; Pharmacokinetics

Indexed keywords

BRIVANIB ALANINATE; DEETHYLLIDOCAINE;

ADULT; ADVERSE OUTCOME; AGED; AREA UNDER THE CURVE; ARTICLE; BILIRUBIN BLOOD LEVEL; CANCER CHEMOTHERAPY; CANCER OF THE LIVER ITALIAN PROGRAM SCORE; CHILD PUGH SCORE; CLINICAL ARTICLE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DECREASED APPETITE; DIARRHEA; DISEASE SEVERITY; DIZZINESS; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSGEUSIA; ESOPHAGUS HEMORRHAGE; FATIGUE; FEMALE; HUMAN; HYPERBILIRUBINEMIA; HYPERKALEMIA; LIVER CELL CARCINOMA; LIVER FUNCTION TEST; MALE; MAXIMUM PLASMA CONCENTRATION; MULTICENTER STUDY; NAUSEA; OUTCOME ASSESSMENT; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; SCORING SYSTEM; SIDE EFFECT; THROMBOCYTE COUNT; TIME TO MAXIMUM PLASMA CONCENTRATION;

AGED; AGED, 80 AND OVER; ALANINE; ANTINEOPLASTIC AGENTS; CARCINOMA, HEPATOCELLULAR; COHORT STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HALF-LIFE; HEPATIC INSUFFICIENCY; HUMANS; LIVER; LIVER NEOPLASMS; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; PATIENT DROPOUTS; PRODRUGS; PROTEIN KINASE INHIBITORS; RECEPTORS, FIBROBLAST GROWTH FACTOR; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; SEVERITY OF ILLNESS INDEX; TRIAZINES;

EID: 84879799535     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-013-2168-z     Document Type: Article

References (27)

1. Korc M, Friesel RE (2009) The role of fibroblast growth factors in tumor growth. Curr Cancer Drug Targets 9(5):639-651
2. Turner N, Grose R (2010) Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer 10(2):116-129
3. Bergers G, Hanahan D (2008) Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 8(8):592-603
4. Tsunoda S, Nakamura T, Sakurai H, Saiki I (2007) Fibroblast growth factor-2-induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A-dependent neovascularization. Cancer Sci 98(4):541-548
5. Giavazzi R, Sennino B, Coltrini D, Garofalo A, Dossi R, Ronca R, Tosatti MP, Presta M (2003) Distinct role of fibroblast growth factor-2 and vascular endothelial growth factor on tumor growth and angiogenesis. Am J Pathol 162(6):1913-1926
6. Casanovas O, Hicklin DJ, Bergers G, Hanahan D (2005) Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 8:299-309
7. Marathe PH, Kamath AV, Zhang Y, D'Arienzo C, Bhide R, Fargnoli J (2009) Preclinical pharmacokinetics and in vitro metabolism of brivanib (BMS-540215), a potent VEGFR2 inhibitor and its alanine ester prodrug brivanib alaninate. Cancer Chemother Pharmacol 65(1):55-66
8. Bhide RS, Cai ZW, Zhang YZ, Qian L, Wei D, Barbosa S, Lombardo LJ, Borzilleri RM, Zheng X, Wu LI, Barrish JC, Kim SH, Leavitt K, Mathur A, Leith L, Chao S, Wautlet B, Mortillo S, Jeyaseelan R Sr, Kukral D, Hunt JT, Kamath A, Fura A, Vyas V, Marathe P, D'Arienzo C, Derbin G, Fargnoli J (2006) Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor. J Med Chem 49(7):2143-2146
9. Huynh H, Ngo VC, Fargnoli J, Ayers M, Soo KC, Koong HN, Thng CH, Ong HS, Chung A, Chow P, Pollock P, Byron S, Tran E (2008) Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma. Clin Cancer Res 14(19):6146-6153
10. Bhide RS, Lombardo LJ, Hunt JT, Cai ZW, Barrish JC, Galbraith S, Jeyaseelan R Sr, Mortillo S, Wautlet BS, Krishnan B, Kukral D, Malone H, Lewin AC, Henley BJ, Fargnoli J (2010) The antiangiogenic activity in xenograft models of brivanib alaninate, a dual inhibitor of VEGFR-2 and FGFR-1 kinases. Mol Cancer Ther 9:369-378
11. Park JW, Finn RS, Kim JS, Karwal M, Li RK, Ismail F, Thomas M, Harris R, Baudelet C, Walters I, Raoul JL (2011) Phase II, open-label study of brivanib as first-line therapy in patients with advanced hepatocellular carcinoma. Clin Cancer Res 17(7):1973-1983
12. Finn RS, Kang YK, Mulcahy M, Polite BN, Lim HY, Walters I, Baudelet C, Manekas D, Park JW (2012) Phase II, open-label study of brivanib as second-line therapy in patients with advanced hepatocellular carcinoma. Clin Cancer Res 18(7):2090-2098
13. Llovet JM, Decaens T, Raoul J-L et al. (2012) Brivanib versus placebo in patients with advanced hepatocellular carcinoma (HCC) who failed or were intolerant to sorafenib: results from the phase 3 BRISK-PS study. Presented at: International Liver Congress™ 2012 - 47th annual meeting of the European Association for the Study of the Liver (EASL); Barcelona, Spain; April 18-22, 2012. Abstract number: A-455-0000-02937
14. National Heart, Lung, and Blood Institute (NHLBI) (2009) A randomized, double-blind, multi-center phase III study of brivanib versus sorafenib as first-line treatment in patients with advanced hepatocellular carcinoma. In: ClinicalTrials.gov [Internet]. National Library of Medicine (US), Bethesda (MD). http://clinicaltrials.gov/ct2/show/NCT00858871
15. BRISK-FL study with investigational compound brivanib in hepatocellular carcinoma does not meet overall survival primary endpoint [news release]. Bristol-Myers Squibb Company. http://news.bms.com/press-release/rd-news/brisk- fl-study-investigational-compound-brivanib-hepatocellular-carcinoma-does. Accessed 17 August 2012
16. Mekhail T, Masson E, Fischer BS, Gong J, Iyer R, Gan J, Pursley J, Patricia D, Williams D, Ganapathi R (2010) Metabolism, excretion, and pharmacokinetics of oral brivanib in patients with advanced or metastatic solid tumors. Drug Metab Dispos 38(11):1962-1966
17. Gong J, Gan J, Iyer RA (2012) Identification of the oxidative and conjugative enzymes involved in the biotransformation of brivanib. Drug Metab Dispos 40(1):219-226
18. Sangiovanni A, Del Ninno E, Fasani P, De Fazio C, Ronchi G, Romeo R, Morabito A, De Franchis R, Colombo M (2004) Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastroenterology 126(4):1005-1014
19. Fattovich G, Stroffolini T, Zagni I, Donato F (2004) Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 127(5 Suppl 1):S35-S50
20. Forner A, Reig ME, de Lope CR, Bruix J (2010) Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis 30(1):61-74
21. The Cancer of Liver Italian Program (CLIP) Investigators (1998) A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients. Hepatology 28(3):751-755
22. US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) (2003) Center for Biologics Evaluation and Research (CBER). Guidance for industry: pharmacokinetics in patients with impaired hepatic function - study design, data analysis and impact on dosing and labeling
23. Testa R, Caglieris S, Risso D, Arzani L, Campo N, Alvarez S, Giannini E, Lantieri PB, Celle G (1997) Monoethylglycinexylidide formation measurement as a hepatic function test to assess severity of chronic liver disease. Am J Gastroenterol 92(12):2268-2273
24. Gong J, Gan J, Caceres-Cortes J, Christopher LJ, Arora V, Masson E, Williams D, Pursley J, Allentoff A, Lago M, Tran SB, Iyer RA (2011) Metabolism and disposition of [14C]brivanib alaninate after oral administration to rats, monkeys, and humans. Drug Metab Dispos 39(5):891-903
25. Hartmann JT, Haap M, Kopp HG, Lipp HP (2009) Tyrosine kinase inhibitors - a review on pharmacology, metabolism and side effects. Curr Drug Metab 10(5):470-481
26. Nexavar [package insert] (2011) Bayer HealthCare Pharmaceuticals Inc., Wayne
27. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J, SHARP Investigators Study Group (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359(4):378-390