A randomized, double-blind, placebo-controlled study to evaluate the effect of repeated oral doses of pazopanib on cardiac conduction in patients with solid tumors

Cancer Chemotherapy and Pharmacology

Volumn 71, Issue 3, 2013, Pages 565-573

  Heath, Elisabeth I ^a   Infante, Jeffrey ^b   Lewis, Lionel D ^c,d   Luu, Thehang ^e   Stephenson, Joe ^f   Tan, Antoinette R ^g   Kasubhai, Saifuddin ^h   Lorusso, Patricia ^a   Ma, Bo ⁱ   Suttle, A Benjamin ⁱ   Kleha, Joseph F ⁱ   Ball, Howard A ⁱ   Dar, Mohammed M ⁱ  

^a WAYNE STATE UNIVERSITY   (United States)

^b SARAH CANNON RESEARCH INSTITUTE   (United States)

^c NORRIS COTTON CANCER CENTER   (United States)

^d DARTMOUTH MEDICAL SCHOOL   (United States)

^e CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^f Children's Hospital   (United States)

^g RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

^h Northwest Medical Specialists ^*  (United States)

ⁱ GLAXOSMITHKLINE   (United States)

Author keywords

Moxifloxacin; Pazopanib; Pharmacokinetics; QTc; Safety; Tyrosine kinase inhibitor

Indexed keywords

MOXIFLOXACIN; PAZOPANIB; PLACEBO; ANGIOGENESIS INHIBITOR; ANTIINFECTIVE AGENT; HETEROCYCLIC COMPOUND; PYRIMIDINE DERIVATIVE; QUINOLINE DERIVATIVE; SULFONAMIDE;

ADULT; ADVANCED CANCER; AGED; ARTICLE; CANCER CHEMOTHERAPY; CHOLANGITIS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DECREASED APPETITE; DIASTOLIC BLOOD PRESSURE; DISEASE ASSOCIATION; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG EFFICACY; DRUG EXPOSURE; DRUG SAFETY; DRUG SCREENING; DRUG WITHDRAWAL; ELECTROCARDIOGRAM; FATIGUE; FEMALE; FIRST DEGREE ATRIOVENTRICULAR BLOCK; HEART ARRHYTHMIA; HEART CONDUCTION; HEART RATE; HOLTER MONITORING; HUMAN; HYPERTENSION; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA; PARALLEL DESIGN; PRIORITY JOURNAL; QT INTERVAL; QT PROLONGATION; RANDOMIZED CONTROLLED TRIAL; RECOMMENDED DRUG DOSE; REPEATED DRUG DOSE; SIDE EFFECT; SINGLE DRUG DOSE; SINUS BRADYCARDIA; SOLID TUMOR; ST SEGMENT DEPRESSION; SUPRAVENTRICULAR PREMATURE BEAT; SYSTOLIC BLOOD PRESSURE; T WAVE; UPPER GASTROINTESTINAL BLEEDING; WEIGHT REDUCTION; ALGORITHM; BLOOD PRESSURE; CHEMICALLY INDUCED DISORDER; CONFIDENCE INTERVAL; CONTROLLED CLINICAL TRIAL; ELECTROCARDIOGRAPHY; HEART MUSCLE CONDUCTION SYSTEM; LONG QT SYNDROME; MIDDLE AGED; NEOPLASM; PATHOPHYSIOLOGY;

ADULT; AGED; ALGORITHMS; ANGIOGENESIS INHIBITORS; ANTI-BACTERIAL AGENTS; AZA COMPOUNDS; BLOOD PRESSURE; CONFIDENCE INTERVALS; DOUBLE-BLIND METHOD; ELECTROCARDIOGRAPHY, AMBULATORY; FEMALE; HEART CONDUCTION SYSTEM; HEART RATE; HUMANS; LONG QT SYNDROME; MALE; MIDDLE AGED; NEOPLASMS; PYRIMIDINES; QUINOLINES; SULFONAMIDES; YOUNG ADULT;

MLCS; MLOWN;

EID: 84875848728     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-012-2030-8     Document Type: Article

References (18)

1. Hutson TE, Davis ID, Machiels JP et al (2010) Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol 28:475-480
2. Sonpavde G, Hutson TE, Sternberg CN (2008) Pazopanib, a potent orally administered small-molecule multitargeted tyrosine kinase inhibitor for renal cell carcinoma. Expert Opin Investig Drugs 17:253-261 (Pubitemid 351578205)
3. Sternberg CN, Davis ID, Mardiak J et al (2010) Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 28:1061-1068
4. Australian Government Department of Health and Ageing (2010) Drugs designated as orphan drugs: Pazopanib (PATORMA). http://www.tga.gov.au/industry/ pm-orphan-drugs.htm. Accessed 23 July 2012
5. Instituto de Salud Publica de Chile (2010) Votrient coated tablets [product registration]. http://200.68.11.21/RegistrosISP/fiFichaProducto.asp? RegistroISP=F-18018/10. Accessed 23 July 2012
6. Kidney Cancer Canada (2010) Votrient (pazopanib) approved by Health Canada for the treatment of renal cell carcinoma. http://www.kidneycancercanada. org/main.php?p=600&lan=1. Accessed 23 July 2012
7. U.S. Department of Health and Human Services Food & Drug Administration (2009) Pazopanib [approval notice]. http://www.fda.gov/AboutFDA/ CentersOffices/CDER/ucm187509.htm. Accessed 23 July 2012
8. European Medicines Agency (2010) Votrient (pazopanib) authorisation details. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/ medicines/001141/human-med-001337.jsp&murl=menus/medicines/medicines. jsp&mid=WC0b01ac058001d124&jsenabled=true. Accessed 23 July 2012
9. Bello CL, Mulay M, Huang X et al (2009) Electrocardiographic characterization of the QTc interval in patients with advanced solid tumors: pharmacokinetic-pharmacodynamic evaluation of sunitinib. Clin Cancer Res 15:7045-7052
10. Desai M, Li L, Desta Z, Malik M, Flockhart D (2003) Variability of heart rate correction methods for the QT interval. Br J Clin Pharmacol 55:511-517 (Pubitemid 36783190)
11. Malik M (2001) Problems of heart rate correction in assessment of drug-induced QT interval prolongation. J Cardiovasc Electrophysiol 12:411-420 (Pubitemid 32324653)
12. Heath EI, Chiorean EG, Sweeney CJ et al (2010) A phase I study of the pharmacokinetic and safety profiles of oral pazopanib with a high-fat or low-fat meal in patients with advanced solid tumors. Clin Pharmacol Ther 88:818-823
13. Goh BC, Reddy NJ, Dandamudi UB et al (2010) An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5 + 1 cocktail in patients with advanced solid tumors. Clin Pharmacol Ther 88:652-659
14. Tolcher AW, Appleman LJ, Shapiro GI, Mita AC, Cihon F, Mazzu A, Sundaresan PR (2011) A phase I open-label study evaluating the cardiovascular safety of sorafenib in patients with advanced cancer. Cancer Chemother Pharmacol 67:751-764
15. Houk BE, Sarapa N, Pithavala YK (2008) Effect of axitinib (AG-013736) concentration on QT interval after administration alone and in combination with ketoconazole in healthy volunteers (abstract PII-36). In: Presented at the 109th annual meeting of the American society for clinical pharmacology and therapeutics
16. U. S. Food and Drug Administration. E14 clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. October 2005, updated 05/26/2009. http://www.fda.gov/RegulatoryInformation/ Guidances/ucm129335.htm. Accessed 23 July 2012
17. Yan LK, Zhang J, Ng MJ, Dang Q (2010) Statistical characteristics of moxifloxacin-induced QTc effect. J Biopharm Stat 20:497-507
18. Chen HX, Cleck JN (2009) Adverse effects of anticancer agents that target the VEGF pathway. Nat Rev Clin Oncol 6:465-477