Axitinib in metastatic renal cell carcinoma: Results of a pharmacokinetic and pharmacodynamic analysis

Journal of Clinical Pharmacology

Volumn 53, Issue 5, 2013, Pages 491-504

  Rini, Brian I ^a   Garrett, May ^b   Poland, Bill ^c   Dutcher, Janice P ^d   Rixe, Olivier ^e   Wilding, George ^f   Stadler, Walter M ^g   Pithavala, Yazdi K ^h   Kim, Sinil ^h   Tarazi, Jamal ^h   Motzer, Robert J ⁱ  

^a TAUSSIG CANCER INSTITUTE   (United States)

^b PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

^c Pharsight   (United States)

^d NEW YORK MEDICAL COLLEGE   (United States)

^e MEDICAL COLLEGE OF GEORGIA   (United States)

^f UNIVERSITY OF WISCONSIN   (United States)

^g UNIVERSITY OF CHICAGO   (United States)

^h PFIZER INC   (United States)

ⁱ MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Axitinib; Diastolic blood pressure; Metastatic renal cell carcinoma; Population pharmacokinetics and pharmacodynamics; VEGF receptor inhibitor

Indexed keywords

AXITINIB; SORAFENIB;

ADULT; AGED; ANTIHYPERTENSIVE THERAPY; AREA UNDER THE CURVE; ARTICLE; BLOOD PRESSURE MEASUREMENT; BODY WEIGHT; CANCER GROWTH; CANCER PATIENT; CANCER PROGNOSIS; DIASTOLIC BLOOD PRESSURE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG TOLERABILITY; ETHNICITY; FEMALE; FIRST PASS EFFECT; HUMAN; JAPANESE; KIDNEY METASTASIS; MAJOR CLINICAL STUDY; MALE; MAXIMUM TOLERATED DOSE; MULTIPLE CYCLE TREATMENT; OVERALL SURVIVAL; PHARMACODYNAMICS; PHARMACOKINETICS; PLASMA CONCENTRATION-TIME CURVE; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SINGLE DRUG DOSE; SOLID TUMOR; TREATMENT RESPONSE;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; CARCINOMA, RENAL CELL; FEMALE; HUMANS; IMIDAZOLES; INDAZOLES; KIDNEY NEOPLASMS; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; PROTEIN KINASE INHIBITORS; RECEPTORS, VASCULAR ENDOTHELIAL GROWTH FACTOR; YOUNG ADULT;

EID: 84880157519     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1002/jcph.73     Document Type: Article

References (40)

1. 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: 7272-7283.
2. KellyRJ, RixeO. Axitinib - a selective inhibitor of the vascular endothelial growth factor(VEGF) receptor.TargetOncol.2009;4:297-305.
3. Choueiri TK. Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. Curr Opin Invest Drugs. 2008;9: 658-671. (Pubitemid 351777169)
4. Tomita Y, Uemura H, Fujimoto H, et al. Key predictive factors of axitinib (AG-013736)-induced proteinuria and efficacy: a phase II study in Japanese patients with cytokine-refractory metastatic renal cell cancer. Eur J Cancer. 2011;47:2592-2602.
5. Rixe O, Bukowski RM, Michaelson MD, et al. Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol. 2007;8:975-984. (Pubitemid 47629888)
6. Rini BI, Wilding G, Hudes G, et al. Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. J Clin Oncol. 2009;27:4462-4468.
7. Cohen EE, Rosen LS, Vokes EE, et al. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: results from a phase II study. J Clin Oncol. 2008;26:4708-4713.
8. Schiller JH, Larson T, Ou SH, et al. Efficacy and safety of axitinib in patients with advanced non-small-cell lung cancer: results from a phase II study. J Clin Oncol. 2009;27:3836-3841.
9. Fruehauf JP, Lutzky J, McDermott DF, et al. Multicenter, phase II study of axitinib, a selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 3, in patients with metastatic melanoma. Clin Cancer Res. 2011;17:7462-7469.
10. 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. 2011;378:1931-1939.
11. Rugo HS, Herbst RS, Liu G, et al. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol. 2005;23:5474- 5483.
12. Larson RA, Druker BJ, Guilhot F, et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood. 2008;111:4022-4028.
13. Houk BE, Bello CL, Poland B, Rosen LS, Demetri GD, Motzer RJ. Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis. Cancer Chemother Pharmacol. 2010;66:357-371.
14. Maitland ML, Kasza KE, Karrison T, et al. Ambulatory monitoring detects sorafenib-induced blood pressure elevations on the first day of treatment. Clin Cancer Res. 2009;15:6250-6257.
15. Rixe O, Billemont B, Izzedine H. Hypertension as a predictive factor of sunitinib activity. Ann Oncol. 2007;18:1117. (Pubitemid 47050505)
16. Scartozzi M, Galizia E, Chiorrini S, et al. Arterial hypertension correlates with clinical outcome in colorectal cancer patients treated with first-line bevacizumab. Ann Oncol. 2009;20:227- 230.
17. Rini BI, Schiller JH, Fruehauf JP, et al. Diastolic blood pressure as a biomarker of axitinib efficacy in solid tumors. Clin Cancer Res. 2011;17:3841-3849.
18. Mukohara T, Nakajima H, Mukai H, et al. Effect of axitinib (AG- 013736) on fatigue, thyroid-stimulating hormone, and biomarkers: a phase I study in Japanese patients. Cancer Sci. 2010;101:963- 968.
19. Rousseau A, Leger F, Le Meur Y, et al. Population pharmacokinetic modeling of oral cyclosporin using NONMEM: comparison of absorption pharmacokinetic models and design of a Bayesian estimator. Ther Drug Monit. 2004;26:23-30. (Pubitemid 38140906)
20. Duval V, Karlsson MO. Impact of omission or replacement of data below the limit of quantification on parameter estimates in a twocompartment model. Pharm Res. 2002;19:1835-1840. (Pubitemid 36016030)
21. Garrett M, Amantea MA, Pithavala Y, Ruiz-Garcia A. Evaluation of the impact of omitting drug concentration data below the lower limit of quantification (LLOQ) on the pharmacokinetics of axitinib (AG-013736), an anti-angiogenic agent. Presented at the 2010 Annual Meeting of the American Society Clinical Pharmacology Therapeutics (ASCPT); March 17-20, 2010; Atlanta, GA.
22. Motzer RJ, Bacik J, Schwartz LH, et al. Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol. 2004;22:454-463. (Pubitemid 41079774)
23. Liu G, Rugo HS, Wilding G, et al. Dynamic contrast-enhanced magnetic resonance imaging as a pharmacodynamic measure of response after acute dosing of AG-013736, an oral angiogenesis inhibitor, in patients with advanced solid tumors: results from a phase I study. J Clin Oncol. 2005;23:5464-5473.
24. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206- 1252. (Pubitemid 37553153)
25. Savic RM, Karlsson MO. Importance of shrinkage in Empirical Bayes estimates for diagnostics: problems solutions. AAPS J. 2009;11:558-569.
26. Ichimaru K, Toyoshima S, Uyama Y. Effective global drug development strategy for obtaining regulatory approval in Japan in the context of ethnicity-related drug response factors. Clin Pharmacol Ther. 2010;87:362-366.
27. Rixe O, Dutcher J, Motzer R, et al. Diastolic blood pressure (dBP) and pharmacokinetics (PK) as predictors of axitinib efficacy in metastatic renal cell cancer (mRCC). J Clin Oncol. 2009;27(15s): abstract 5045.
28. Pithavala YK, Chen Y, Toh M, et al. Evaluation of the effect of food on the pharmacokinetics of axitinib in healthy volunteers. Cancer Chemother Pharmacol. 2012;70:103-112.
29. Pithavala YK, Tortorici M, Toh M, et al. Effect of rifampin on the pharmacokinetics of axitinib (AG-013736) in Japanese and Caucasian healthy volunteers. Cancer Chemother Pharmacol. 2010;65:563-570.
30. Tortorici MA, Toh M, Rahavendran SV, et al. Influence of mild and moderate hepatic impairment on axitinib pharmacokinetics. Invest New Drugs. 2011;29:1370-1380.
31. Zhu X, Wu S, Dahut WL, Parikh CR. Risks of proteinuria and hypertension with bevacizumab, an antibody against vascular endothelial growth factor: systematic review and meta-analysis. Am J Kidney Dis. 2007;49:186-193. (Pubitemid 46178407)
32. Wu S, Chen JJ, Kudelka A, Lu J, Zhu X. Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis. Lancet Oncol. 2008;9:117-123.
33. Zhu X, Stergiopoulos K, Wu S. Risk of hypertension and renal dysfunction with an angiogenesis inhibitor sunitinib: systematic review and meta-analysis. Acta Oncol. 2009;48:9-17.
34. 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.
35. Veronese ML, Mosenkis A, Flaherty KT, et al. Mechanisms of hypertension associated with BAY 43-9006. J Clin Oncol. 2006;24:1363-1369. (Pubitemid 46621999)
36. Kamba T, McDonald DM. Mechanisms of adverse effects of anti- VEGF therapy for cancer. Br J Cancer. 2007;96:1788-1795. (Pubitemid 46912024)
37. Mourad JJ, des Guetz G, Debbabi H, Levy BI. Blood pressure rise following angiogenesis inhibition by bevacizumab.A crucial role for microcirculation. Ann Oncol. 2008;19:927-934. (Pubitemid 351627309)
38. Azizi M, Chedid A, Oudard S. Home blood-pressure monitoring in patients receiving sunitinib. N Engl J Med. 2008;358: 95-97.
39. Pithavala YK, Tong W, Mount J, et al. Effect of ketoconazole on the pharmacokinetics of axitinib in healthy volunteers. Invest New Drugs. 2012;30:273-281.
40. Chen Y, Jiang J, Zhang J, et al. A Phase I study to evaluate the pharmacokinetics of axitinib (AG-13736) in healthy Chinese volunteers. Int J Clin Pharmacol Ther. 2011;49:679-687.