A single-dose placebo- and moxifloxacin-controlled study of the effects of temsirolimus on cardiac repolarization in healthy adults

Cancer Chemotherapy and Pharmacology

Volumn 69, Issue 6, 2012, Pages 1433-1442

  Boni, Joseph P ^a   Leister, Cathie ^a   Hug, Bruce ^a   Burns, Jaime ^a   Sonnichsen, Daryl ^a  

^a PFIZER INC   (United States)

Author keywords

Cardiac arrhythmia; Drug safety; MTOR; Renal cell carcinoma; Targeted therapy; Temsirolimus

Indexed keywords

MOXIFLOXACIN; PLACEBO; RAPAMYCIN; TEMSIROLIMUS;

ACNE; ADULT; APHTHOUS STOMATITIS; APPLICATION SITE REACTION; AREA UNDER THE CURVE; ARTICLE; CARDIOVASCULAR EFFECT; CONTACT DERMATITIS; CONTROLLED STUDY; CROSSOVER PROCEDURE; DRUG BLOOD LEVEL; DRUG ERUPTION; DRUG EXPOSURE; DRUG INDUCED HEADACHE; DRUG INFUSION; DRUG SAFETY; ELECTROCARDIOGRAM; FEMALE; HEART RATE; HEART REPOLARIZATION; HEART VENTRICLE FIBRILLATION; HEART VENTRICLE FLUTTER; HUMAN; HUMAN EXPERIMENT; LIQUID CHROMATOGRAPHY; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; OPEN STUDY; PHARMACODYNAMICS; PRIORITY JOURNAL; QT INTERVAL; QT PROLONGATION; RECOMMENDED DRUG DOSE; SEIZURE; SENSITIVITY ANALYSIS; SIDE EFFECT; SINGLE BLIND PROCEDURE; SINGLE DRUG DOSE; STOMATITIS; SYNCOPE; TANDEM MASS SPECTROMETRY; TIME TO MAXIMUM PLASMA CONCENTRATION; TORSADE DES POINTES;

ADOLESCENT; ADULT; ANTI-INFECTIVE AGENTS; ANTINEOPLASTIC AGENTS; AZA COMPOUNDS; CROSS-OVER STUDIES; CYTOCHROME P-450 CYP3A; ELECTROCARDIOGRAPHY; FEMALE; HUMANS; MALE; MIDDLE AGED; PLACEBOS; PROTEIN KINASE INHIBITORS; QUINOLINES; SINGLE-BLIND METHOD; SIROLIMUS;

EID: 84863791392     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-012-1845-7     Document Type: Article

References (27)

1. Farkas AS, Nattel S (2010) Minimizing repolarization-related proarrhythmic risk in drug development and clinical practice. Drugs 70:573-603
2. Salvi V, Karnad DR, Panicker GK, Kothari S (2010) Update on the evaluation of a new drug for effects on cardiac repolarization in humans: issues in early drug development. Br J Pharmacol 159:34-48
3. Shah RR (2002) The significance of QT interval in drug development. Br J Clin Pharmacol 54:188-202
4. Abraham RT, Gibbons JJ (2007) The mammalian target of rapamycin signaling pathway: twists and turns in the road to cancer therapy. Clin Cancer Res 13:3109-3114
5. Boni JP, Hug B, Leister C, Sonichsen D (2009) Intravenous temsirolimus in cancer patients: clinical pharmacology and dosing considerations. Semin Oncol 36:S18-S25
6. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A, Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt-Wolf I, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer R, Global ARCC Trial (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271-2281
7. Food and Drug Administration (2005) International Conference on Harmonisation; guidance on E14 clinical evaluation of QT/ QTc interval prolongation and proarrhythmic potential for nonantiarrhythmic drug. Fed Regist 70:61134-61135
8. Hug B, Abbas R, Leister C, Burns J, Sonnichsen D (2010) A single-dose, crossover, placebo- and moxifloxacin-controlled study to assess the effects of neratinib (HKI-272) on cardiac repolarization in healthy adult subjects. Clin Cancer Res 16: 4016-4023
9. Boni J, Leister C, Burns J, Cincotta M, Hug B, Moore L (2007) Pharmacokinetic profile of temsirolimus with concomitant administration of cytochrome P450-inducing medications. J Clin Pharmacol 47:1430-1439
10. Boni J, Abbas R, Leister C, Burns J, Jordan R, Hoffmann M, DeMaio W, Hug B (2009) Disposition of desipramine, a sensitive cytochrome P450 2D6 substrate, when coadministered with intravenous temsirolimus. Cancer Chemother Pharmacol 64: 263-270
11. Torisel [package insert] (2011) Pfizer Inc, Philadelphia
12. Avelox [package insert] (2008) Bayer HealthCare Pharmaceuticals, Wayne
13. Punt CJ, Boni J, Bruntsch U, Peters M, Thielert C (2003) Phase I and pharmacokinetic study of CCI-779, a novel cytostatic cellcycle inhibitor, in combination with 5-fluorouracil and leucovorin in patients with advanced solid tumors. Ann Oncol 14:931-937
14. Evans WE, Schentag JJ, Jusko WJ (eds) (1992) Applied pharmacokinetics: principles of therapeutic drug monitoring. Lippincott Williams & Wilkins, New York
15. Zareba W, Moss AJ, Rosero SZ, Hajj-Ali R, Konecki J, Andrews M (1997) Electrocardiographic findings in patients with diphenhydramine overdose. Am J Cardiol 80:1168-1173
16. Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, Hudes GR, Park Y, Liou SH, Marshall B, Boni JP, Dukart G, Sherman ML (2004) Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol 22:909-918
17. Boni JP, Leister C, Burns J, Hug B (2008) Differential effects of ketoconazole on exposure to temsirolimus following intravenous infusion of temsirolimus. Br J Cancer 98:1797-1802
18. Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, Laurell A, Offner F, Strahs A, Berkenblit A, Hanushevsky O, Clancy J, Hewes B, Moore L, Coiffier B (2009) Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 27:3822-3829
19. Benton RE, Sale M, Flockhart DA, Woosley RL (2000) Greater quinidine-induced QTc interval prolongation in women. Clin Pharmacol Ther 67:413-418
20. Boni JP, Leister C, Bender G, Fitzpatrick V, Twine N, Stover J, Dorner A, Immermann F, Burczynski ME (2005) Population pharmacokinetics of CCI-779: correlations to safety and pharmacogenomic responses in patients with advanced renal cancer. Clin Pharmacol Ther 77:76-89
21. Boni JP, Zhou S, Burns J, Smith K, Liao S (2006) Integrated population pharmacokinetic analysis of temsirolimus in cancer patients following weekly IV treatments [abstract 552]. Eur J Cancer Suppl 4:167
22. Schmidinger M, Zielinski CC, Vogl UM, Bojic A, Bojic M, Schukro C, Ruhsam M, Hejna M, Schmidinger H (2008) Cardiac toxicity of sunitinib and sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 26:5204-5212
23. Force T, Krause DS, Van Etten RA (2007) Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat Rev Cancer 7:332-344
24. Girardi F, Franceschi E, Brandes AA (2010) Cardiovascular safety of VEGF-targeting therapies: current evidence and handling strategies. Oncologist 15:683-694
25. Bello CL, Mulay M, Huang X, Patyna S, Dinolfo M, Levine S, Van VA, Toh M, Baum C, Rosen L (2009) Electrocardiographic characterization of the QTc interval in patients with advanced solid tumors: pharmacokinetic- pharmacodynamic evaluation of sunitinib. Clin Cancer Res 15:7045-7052
26. Keisner SV, Shah SR (2011) Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs 71:443-454
27. 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