A phase I study to evaluate the pharmacokinetics of axitinib (AG-13736) in healthy Chinese volunteers

International Journal of Clinical Pharmacology and Therapeutics

Volumn 49, Issue 11, 2011, Pages 679-687

  Chen, Y ^a   Jiang, J ^b   Zhang, J ^b   Tortorici, M A ^a   Pithavala, Y K ^a   Lu, L ^a   Ni, G ^a   Hu, P ^b  

^a PFIZER INC   (United States)

^b PEKING UNION MEDICAL COLLEGE HOSPITAL   (China)

Author keywords

Axitinib; Chinese; Pharmacokinetics; Tolerability; Vascular endothelial growth factor receptor inhibitor

Indexed keywords

AXITINIB;

ADULT; AREA UNDER THE CURVE; ARTICLE; CAUCASIAN; CHINESE; CLINICAL EVALUATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG MONITORING; DRUG SAFETY; DRUG TOLERABILITY; ETHNIC DIFFERENCE; FEMALE; HUMAN; HUMAN EXPERIMENT; MALE; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT;

ADULT; ANGIOGENESIS INHIBITORS; AREA UNDER CURVE; FEMALE; HUMANS; IMIDAZOLES; INDAZOLES; MALE;

EID: 80054779985     PISSN: 09461965     EISSN: None     Source Type: Journal    
DOI: 10.5414/CP201570     Document Type: Article

References (34)

1. Choueiri TK. Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. Curr Opin Investig Drugs. 2008; 9: 658-671. PubMed (Pubitemid 351777169)
2. Hu-Lowe DD, Zou HY, Grazzini ML, Hallin ME, Wickman GR, Amundson K, Chen JH, Rewolinski DA, Yamazaki S, Wu EY, McTigue MA, Murray BW, Kania RS, O'Connor P, Shalinsky DR, Bender SL. 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. doi:10.1158/1078-0432.CCR-08-0652 PubMed
3. Rixe O, Bukowski RM, Michaelson MD, Wilding G, Hudes GR, Bolte O, Motzer RJ, Bycott P, Liau KF, Freddo J, Trask PC, Kim S, Rini BI. Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. Lancet Oncol. 2007; 8: 975-984. doi:10.1016/S1470-2045(07)70285-1 PubMed (Pubitemid 47629888)
4. Rini BI, Wilding G, Hudes G, Stadler WM, Kim S, Tarazi J, Rosbrook B, Trask PC, Wood L, Dutcher JP. Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. J Clin Oncol. 2009; 27: 4462-4468. doi:10.1200/JCO.2008.21.7034 PubMed
5. Schiller JH, Larson T, Ou SHJ, Limentani S, Sandler A, Vokes E, Kim S, Liau K, Bycott P, Olszanski AJ, von Pawel J. 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. doi:10.1200/JCO.2008.20.8355 PubMed
6. Cohen EE, Rosen LS, Vokes EE, Kies MS, Forastiere AA, Worden FP, Kane MA, Sherman E, Kim S, Bycott P, Tortorici M, Shalinsky DR, Liau KF, Cohen RB. 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. doi:10.1200/JCO.2007.15.9566 PubMed
7. Rugo HS Stopeck AT, Joy AA, Chan S, Verma S, Lluch A, Liau KF, Kim S, Bycott B, Rosbrook B, Bair AH, Soulieres D. Randomized, placebo-controlled, double-blind, Phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer. J Clin Oncol. 2011; 29: 2459-2465. http://www.ncbi.nlm.nih.gov/pubmed?term= j+clin+oncol%5BJour%5D+AND+29%5Bvolume%5D+AND+2459%5Bpage%5D&cmd= detailssearch
8. Fruehauf J, Lutzky J, McDermott DF, Brown CK, Pithavala YK, Bycott PW, Shalinsky D, Liau KF, Niethammer A, Rixe O. Axitinib (AG-013736) in patients with metastatic melanoma: A phase II study. J Clin Oncol. 2008; 26: 15 (suppl; abstract 9006).
9. Kindler HL, Ioka T, Richel DJ, Bennouna J, Létourneau R, Okusaka T, Funakoshi A, Furuse J, Park YS, Ohkawa S, Springett GM, Wasan HS, Trask PC, Bycott P, Ricart AD, Kim S, Van Cutsem E. Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study. Lancet Oncol. 2011; 12: 256-262. doi:10.1016/S1470-2045(11)70004-3 PubMed
10. Sharma S, Abhyankar V, Burgess RE, Infante J, Trowbridge RC, Tarazi J, Kim S, Tortorici M, Chen Y, Robles RL. A phase I study of axitinib (AG-013736) in combination with bevacizumab plus chemotherapy or chemotherapy alone in patients with metastatic colorectal cancer and other solid tumors. Ann Oncol. 2010; 21: 297-304. doi:10.1093/annonc/mdp489 PubMed
11. Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, Pithavala YK, Reich SD, Freddo JL, Wilding G. 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. doi:10.1200/JCO.2005.04.192 PubMed
12. Tortorici M, Chen Y, Hee B, Ni G, Pithavala YK. Effect of food on the pharmacokinetics of axitinib in healthy volunteers (HVs). Presented at the European Association for Cancer Research Meeting, 2010, Oslo, Norway.
13. Pithavala YK, Tortorici M, Toh M, Garrett M, Hee B, Kuruganti U, Ni G, Klamerus KJ. Effect of rifampin on the pharmacokinetics of Axitinib (AG-013736) in Japanese and Caucasian healthy volunteers. Cancer Chemother Pharmacol. 2010; 65: 563-570. doi:10.1007/s00280-009-1065-y PubMed
14. Fujiwara Y, Kiyota N, Chayahara N, Suzuki A, Umeyama Y, Mukohara T, Minami H. Management of axitinib (AG-013736)-induced fatigue and thyroid dysfunction, and predictive biomarkers of axitinib exposure: results from phase I studies in Japanese patients. Invest New Drugs. 2011; Feb 8. [Epub ahead of print]. PubMed
15. Pithavala YK, Tong W, Mount J, Rahavendran SV, Garrett M, Hee B, Selaru P, Sarapa N, Klamerus KJ. Effect of ketoconazole on the pharmacokinetics of axitinib in healthy volunteers. Invest New Drugs. 2010; Aug 26 [Epub ahead of print].
16. Crettol S, Petrovic N, Murray M. Pharmacogenetics of phase I and phase II drug metabolism. Curr Pharm Des. 2010; 16: 204-219. doi:10.2174/ 138161210790112674 PubMed
17. Ozawa S, Soyama A, Saeki M, Fukushima-Uesaka H, Itoda M, Koyano S, Sai K, Ohno Y, Saito Y, Sawada J. Ethnic differences in genetic polymorphisms of CYP2D6, CYP2C19, CYP3As and MDR1/ABCB1. Drug Metab Pharmacokinet. 2004; 19: 83-95. doi:10.2133/dmpk.19.83 PubMed
18. Monaghan G, Ryan M, Seddon R, Hume R, Burchell B. Genetic variation in bilirubin UPD-glucuronosyltransferase gene promoter and Gilbert's syndrome. Lancet. 1996; 347: 578-581. doi:10.1016/S0140-6736(96)91273-8 PubMed (Pubitemid 26070740)
19. Balram C, Sabapathy K, Fei G, Khoo KS, Lee EJ. Genetic polymorphisms of UDP-glucuronosyltrans ferase in Asians: UGT1A1*28 is a common allele in Indians. Pharmacogenetics. 2002; 12: 81-83. doi:10.1097/00008571-200201000-00012 PubMed (Pubitemid 34112247)
20. Tortorici MA, Tho M, Rahavendran SV, Labadie RR, Alvey CW, Marbury T, Fuentes E, Green M, Ni G, Hee B, Pithavala YK. Influence of mild and moderate hepatic impairment on axitinib pharmacokinetics. Invest New Drugs. 2010; Jul 2. [Epub ahead of print]
21. Sparidans RW, Iusuf D, Schinkel AH, Schellens JH, Beijnen J. H. Liquid chromatography-tandem mass spectrometric assay for the light sensitive tyrosine kinase inhibitor axitinib in human plasma. J Chromatogr A. 2009; 877: 4090-4096.
22. Mukohara T, Nakajima H, Mukai H, Nagai S, Itoh K, Umeyama Y, Hashimoto J, Minami H. 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. doi:10.1111/j.1349-7006.2009.01465.x PubMed
23. Singh BN, Malhotra BK. Effects of food on the clinical pharmacokinetics of anticancer agents: underlying mechanisms and implications for oral chemotherapy. Clin Pharmacokinet. 2004; 43: 1127-1156. doi:10.2165/00003088- 200443150-00005 PubMed (Pubitemid 40013180)
24. Lal S, Wong ZW, Jada SR, Xiang X, Chen Shu X, Ang PC, Figg WD, Lee EJ, Chowbay B. Novel SLC22A16 polymorphisms and influence on doxorubicin pharmacokinetics in Asian breast cancer patients. Pharmacogenomics. 2007; 8: 567-575. doi:10.2217/14622416.8.6.567 PubMed (Pubitemid 46939582)
25. Kim K, Johnson JA, Derendorf H. Differences in drug pharmacokinetics between East Asians and Caucasians and the role of genetic polymorphisms. J Clin Pharmacol. 2004; 44: 1083-1105. doi:10.1177/0091270004268128 PubMed (Pubitemid 39202454)
26. Hor SY, Lee SC, Wong CI, Lim YW, Lim RC, Wang LZ, Fan L, Guo JY, Lee HS, Goh BC, Tan T. PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients. Pharmacogenomics J. 2008; 8: 139-146. doi:10.1038/sj.tpj.6500478 PubMed (Pubitemid 351411550)
27. Lind JS, Dingemans AM, Groen HJ, Thunnissen FB, Bekers O, Heideman DA, Honeywell RJ, Giovannetti E, Peters GJ, Postmus PE, van Suylen RJ, Smit EF. A multicenter phase II study of erlotinib and sorafenib in chemotherapy-naive patients with advanced non-small cell lung cancer. Clin Cancer Res. 2010; 16: 3078-3087. doi:10.1158/1078-0432.CCR-09-3033 PubMed
28. van Erp NP, Eechoute K, van der Veldt AA, Haanen JB, Reyners AK, Mathijssen RH, Boven E, van der Straaten T, Baak-Pablo RF, Wessels JA, Guchelaar HJ, Gelderblom H. Pharmacogenetic pathway analysis for determination of sunitinib-induced toxicity. J Clin Oncol. 2009; 27: 4406-4412. doi:10.1200/JCO.2008.21.7679 PubMed
29. Chen L, Qin S, Xie J, Tang J, Yang L, Shen W, Zhao X, Du J, He G, Feng G, He L, Xing Q. Genetic polymorphism analysis of CYP2C19 in Chinese Han populations from different geographic areas of mainland China. Pharmacogenomics. 2008; 9: 691-702. doi:10.2217/14622416.9.6.691 PubMed
30. Karatzas A, Giannatou E, Tzortzis V, Gravas S, Aravantinos E, Moutzouris G, Melekos M, Tsezou A. Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and prostate cancer risk in Caucasian men. Cancer epidemiology. 2010; 34: 345-349.
31. Liu JY, Qu K, Sferruzza AD, Bender RA. Distribution of the UGT1A1*28 polymorphism in Caucasian and Asian populations in the US: a genomic analysis of 138 healthy individuals. Anticancer Drugs. 2007; 18: 693-696. doi:10.1097/CAD.0b013e32803a46fe PubMed (Pubitemid 47343662)
32. Shu Y, Zhou HH. Individual and ethnic differences in CYP2C19 activity in Chinese populations. Acta Pharmacol Sin. 2000; 21: 193-199. PubMed (Pubitemid 30160975)
33. Zhou YY, Lee LY, Ng SY, Hia CP, Low KT, Chong YS, Goh DL. UGT1A1 haplotype mutation among Asians in Singapore. Neonatology. 2009; 96: 150-155. doi:10.1159/000209851 PubMed
34. Garrett M, Houk BE, Myrand SP, Hee B, Mota J, Pithavala YK. A population pharmacokinetic (PK) analysis to evaluate the potential effect of the UGT1A1*28 genotype on the PK of AG-013736, an antiangiogenic agent. Presented at the American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting, 2007, Anaheim, California.