Understanding disease-drug interactions in cancer patients: Implications for dosing within the therapeutic window

Clinical Pharmacology and Therapeutics

Volumn 98, Issue 1, 2015, Pages 76-86

  Coutant, D E ^a   Kulanthaivel, P ^a   Turner, P K ^a   Bell, R L ^a   Baldwin, J ^a   Wijayawardana, S R ^a   Pitou, C ^a   Hall, S D ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALBUMIN; BIOLOGICAL MARKER; C REACTIVE PROTEIN; CYTOCHROME P450; DRUG METABOLIZING ENZYME; ENZASTAURIN; INTERLEUKIN 1BETA; INTERLEUKIN 6; MIDAZOLAM; MITOGEN ACTIVATED PROTEIN KINASE P38; OROSOMUCOID; TUMOR NECROSIS FACTOR ALPHA; ACUTE PHASE PROTEIN; CYTOKINE; IMIDAZOLE DERIVATIVE; INDOLE DERIVATIVE; LY2228820; PROTEIN KINASE C BETA; PYRIDINE DERIVATIVE;

ACETYLATION; ADVANCED CANCER; AREA UNDER THE CURVE RATIO; CANCER PATIENT; CASE STUDY; CONJUGATION; DISEASE MARKER; DRUG CLEARANCE; DRUG EXPOSURE; DRUG INTERACTION; DRUG METABOLISM; ENZYME ACTIVITY; GENE EXPRESSION; GLUCURONIDATION; HUMAN; INFLAMMATION; INTRINSIC CLEARANCE; MAXIMUM PLASMA CONCENTRATION; META ANALYSIS (TOPIC); METHYLATION; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PLASMA CLEARANCE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; REVIEW; SULFATION; ANTAGONISTS AND INHIBITORS; IMMUNOLOGY; METABOLISM; NEOPLASM;

ACUTE-PHASE PROTEINS; CYTOCHROME P-450 ENZYME SYSTEM; CYTOKINES; DRUG INTERACTIONS; HUMANS; IMIDAZOLES; INDOLES; INFLAMMATION; META-ANALYSIS AS TOPIC; MIDAZOLAM; NEOPLASMS; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PROTEIN KINASE C BETA; PYRIDINES;

EID: 84940515765     PISSN: 00099236     EISSN: 15326535     Source Type: Journal    
DOI: 10.1002/cpt.128     Document Type: Review

References (66)

1. Morgan E.T, et al. Symposium report: Regulation of drugmetabolizing enzymes, and transporters in infection, inflammation, and cancer. Drug. Metab. Disp. 36, 205-216 (2008).
2. Harvey R.D, & Morgan E.T. Cancer, inflammation, and therapy: effects on cytochrome P450-mediated drug metabolism and implications for novel immunotherapeutic agents. Clin. Pharm. Ther. 96(4), 449-457 (2014).
3. Kacevska M, Robertson G.R, Clarke S.J, & Liddle C. Inflammation and CYP3A4-mediated drug metabolism in advanced cancer: impact and implications for chemotherapeutic drug dosing. Expert Opin. Drug Metab. Toxicol. 4(2), 137-149 (2008).
4. Cressman A.M, Petrovic V, & Piquette-Miller M. Inflammationmediated changes in drug transporter expression/activity: implications for therapeutic drug response. Expert Rev. Clin. Pharmacol. 5(1), 69-89 (2012).
5. Chua W, Clarke S.J, & Charles K.A. Systemic inflammation and prediction of chemotherapy outcomes in patients receiving docetaxel for advanced cancer. Support Care Cancer. 8, 1869-1874 (2011).
6. Martin F, et al. Cytokine levels (Il-6, and IFN-g), acute phase response and nutritional status as prognostic factors in lung cancer. Cytokine. 11(1), 80-86 (1999).
7. Morgan E.T. Impact of infectious, and inflammatory disease on cytochrome p450-mediated drug metabolism, and pharmacokinetics. Clin. Pharmacol. Ther. 85(4), 434-438 (2009).
8. Berg-Candolfi M, Candolfi E, & Benet L.Z. Suppression of intestinal and hepatic cytochrome P4503A in murine Toxoplasma infection. Effects of N-Acetylcysteine, and NG-monomethyl-L-Arginine on the hepatic expression. Xenobiotica. 36(4), 381-394 (1996).
9. Kawaguchi H, Matsui Y, Watanabe Y, & Takakura Y. Effect of interferon-g on the pharmacokinetics of digoxin, a P-glycoprotein substrate, intravenously injected the mouse. J. Pharmacol. Exp. Ther. 308(1), 91-96 (2003).
10. Lang C.C, et al. Decreased intestinal CYP3A in celiac disease: reversal after successful gluten-free diet; a potential source of interindividual variability in first-pass drug metabolism. Clin. Pharmacol. Ther. 59, 41-46 (1996).
11. Tegude H, et al. Molecule mechanism of basal CYP3A4 regulation by hepatocyte nuclear factor 4a: evidence for direct regulation in the intestine. Drug Metab. Disp. 35, 946-954 (2007).
12. Rowland A, Miners J.O, & Mackenzie P.I. The UDPglucuronosyltransferases: their role in drug metabolism and detoxification. Int. J. Biochem. Cell Biol. 45, 1121-1132 (2013).
13. Strasser S.L, Mashford M.L, & Desmond P.V. Regulation of uridine diphosphate glucuronosyltransferase during the acute phase response. J. Gastroenterol. Hepatol. 13, 88-94 (1998).
14. Panaro M.A, Cavallo P, Acquafredda A, Cianciulli A, Caivello R, & Mitollo V. Expression of UDP-glucuronosyltransferase 1A6 isoform in Caco-2 cells stimulated with lipopolysaccharide. Innate Immun. 16(5), 302-309 (2010).
15. Lévesque E, Beaulieu M, Guillemette C, & Bélanger A. Effect of interleukins on UGT2B15, and UGT2B17 steroid uridine diphosphateglucuronosyltransferase expression, and activity in the LNCaP cell line. Endocrinology 139(5), 2375-2381 (1998).
16. Giuliani L, et al. UDP-glucuronosyltransferases 1A expression in human urinary bladder, and colon cancer by immunohistochemistry. Oncol. Rep. 13, 185-191 (2005).
17. Englund G, Jacobson A, Rorsman F, Artursson P, Kindmark A, & R€onnblom A. Efflux transporters in ulcerative colitis: decreased expression of BCRP (ABCG2), and Pgp (ABCB1). Inflamm. Bowel Dis. 13(3), 291-297 (2007).
18. Wojtal K.A, et al. Changes in mRNA expression levels of solute carrier transporters in inflammatory bowel disease patients. Drug Metab. Disp. 37(9), 1871-1877 (2009).
19. Kim, D-Y, et al. Clinical significances of preoperative serum interleukin-6, and C-reactive protein level inoperable gastric cancer. BMC Cancer. 9, 155-163 (2009).
20. Koukkunen H, et al. C-reactive protein, fibrinogen, interleukin-6 and tumour necrosis factor-A in the prognostic classification of unstable angina pectoris. Ann. Med. 33, 37-47 (2001).
21. Rivory L.P, Slaviero K.A, & Clarke S.J. Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acutephase response. Br. J. Cancer. 87, 277-280 (2002).
22. Machavaram K.K, et al. A physiologically based pharmacokinetic modeling approach to predict disease-drug interactions: suppression of CYP3A by IL-6. Clin. Pharmacol. Ther. 94(2), 260-268 (2013).
23. Benet L.Z, & Hoener B. Changes in plasma protein binding have little clinical relevance. Clin. Pharmacol. Ther. 71(3), 115-121 (2002).
24. Smith D.A, & Kerns E.H. The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery. Nat. Rev. 9, 929-939 (2010).
25. Charles. K.A, et al. Predicting the toxicity of weekly docetaxel in advanced cancer. Clin. Pharmacokinet. 45(6), 611-622 (2006).
26. Bruno R, et al. Alpha-1-Acid glycoprotein as an independent predictor for treatment effects, and a prognostic factor of survival in patients with non-small cell lung cancer treated with docetaxel. Clin. Cancer Res. 9(3), 1077-1082 (2003).
27. Kayacan O, et al. Impact of TNF-A, and IL-6 levels on development of cachexia in newly diagnosed NSCLC patients. Am. J. Clin. Oncol. 29(4), 328-335 (2006).
28. Proctor M.J, et al. A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow inflammation outcome study. Eur. J. Cancer 47(17), 2633-2641 (2011).
29. Slaviero K.A, Clarke S.J, & Rivory L.P. Inflammatory response: an unrecognized source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet. 4, 224-232 (2003).
30. Morgan E.T. Regulation of cytochromes P450 during inflammation and infection. Drug Metab. Rev. 29(4), 1129-1188 (1997).
31. Robertson G.R, Liddle C, & Clarke S.J. Inflammation, and altered drug clearance in cancer: transcriptional repression of a human CYP3A4 transgene in tumor-bearing mice. Clin. Pharmacol. Ther. 83(6), 894-897 (2008).
32. Manicourt, D-H, et al. Levels of circulating tumor necrosis factor-A and interleukin-6 in patients with rheumatoid arthritis. Arthritis Rheum. 36(4), 490-498 (1993).
33. Shedlofsky S.I, et al. Endotoxin administration to humans inhibits hepatic cytochrome P450-mediated drug metabolism. J. Clin. Invest. 94, 2209-2214 (1994).
34. Arican O, Aral M, Sasmaz S, & Giragil P. Serum levels of TNF-A, IFN-g, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis, and correlation with disease severity. Mediat. Inflamm. 2005(5), 273-279 (2005).
35. Bal A, Unlu E, Bahar G, Aydog E, Eksioglu E, & Yorgancioglu R. Comparison of serum Il-1b, sIL-2R, IL-6, and TNF-A levels with disease activity parameters in ankylosing spondylitis. Clin. Rheumatol. 26, 211-215 (2007).
36. Belec L, Meillet D, Hernvann A, Grésenguet G, & Gherardi R. Differential elevation of circulating interleukin-1b, tumor necrosis factor alpha, and interleukin-6 in AIDS-Associated cachectic states. Clin. Diagn. Lab. Immunol. 1(1), 117-120 (1994).
37. Chung, S-J, Kwon, Y-J, Park, M-C, Park, Y-B, & Lee, S-K. The correlation between increased serum concentrations of interleukin-6 family cytokines, and disease activity in rheumatoid arthritis patients. Yonsei Med. J. 52(1), 113-120 (2011).
38. Dogan Y, Akarsu S, Ustundag B, Yilmaz E, & Gurgoze M.K. Serum Il-1b, Il-2, and IL-6 in insulin-dependent diabetic children. Mediat. Inflamm. 2006, 1-6 (2006).
39. Domaç, F.M, Somay G, Misirli H, & Erenoglu N.Y. Tumor necrosis factor alpha serum levels, and inflammatory response in acute ischemic stroke. Neuroscience 12(1), 25-30 (2007).
40. Ebrahimi A.A, et al. Serum levels of TNF-A, TNF-ARI, TNF-ARII, and IL-12 in treated rheumatoid arthritis patients. Iran. J. Immunol. 6(3), 147-153 (2009).
41. Hong M, Wei W, Hu Y, Yang R, & Yang Y. Plasma levels of the anti-inflammatory cytokine IL-10, and inflammatory cytokine IL-6 in patients with unstable angina. J. Huazhong Univ. Sci. Technol. Med. Sci. 25(6), 639-641 (2005).
42. Karayiannakis A, Syrigos K.N, Polychrondidis A, Pitiakoudis M, Bounovas A, & Simopoulos K. Serum levels of tumor necrosis factor-A, and nutritional status in pancreatic cancer patients. Anticancer Res. 21, 1355-1358 (2001).
43. Linderholm M, Ahim C, Settergren B, Wagne A, & Tarnvik A. Elevated plasma levels of tumor necrosis factor (TNF)-A, soluble TNF receptors, interleukin (IL)-6, and IL-10 in patients with hemorrhagic fever with renal syndrome. J. Infect. Dis. 173, 38-43 (1996).
44. Lutgendorf S.K, et al. Interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients. J. Clin. Oncol. 26(29), 4820-4826 (2008).
45. Ozeren A, et al. Levels of serum Il-1b, Il-2, IL-8, and tumor necrosis factor-A in patients with unstable angina pectoris. Mediat. Inflamm. 12(6), 361-365 (2003).
46. Shariat S.F, Andrews B, Kaitan M.W, Kim J, Wheeler T.M, & Slawin K.M. Plasma levels of interleukin-6, and its soluble receptor are associated with prostate cancer progression, and metastasis. Urology. 58(6), 1008-1015 (2001).
47. Spadaro A, Taccari E, Riccieri, V, Sensi F, Scavalli A.S, & Zoppini A. Interleukin-6, and soluble interleukin-2-receptor in psoriatic arthritis: correlations with clinical, and laboratory parameters. Clin. Exp. Rheum. 14, 413-416 (1996).
48. Tsutamoto T, et al. Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. Am. Coll. Cardiol. 31(2), 391-398 (1998).
49. Pavese I, et al. High serum levels of TNF-A, and IL-6 predict the clinical outcome of treatment with human recombinant erythropoietin in anaemic cancer patients. Ann. Oncol. 21(7), 1523-1528 (2010).
50. Hocaoglu C, Kural B, Aliyazicioglu R, Deger O, & Cengiz S. IL-Ib, IL-6, IL-8, IL-10, IFN-g, TNF-A, and its relationship with lipid parameters in patients with major depression. Metab. Brain Dis. 27(4), 425-430 (2012).
51. Lopes C.O, & Callera F. Three-dimensional conformal radiotherapy in prostate cancer patients: rise in interleukin 6 (IL-6) but not IL-2, IL-4, IL-5, tumor necrosis factor-A, MIP-1-A, and LIF levels. Int. J. Radiat. Oncol. Biol. Phys. 82(4), 1385-1388 (2012).
52. Iwase S, Murakami T, Saito Y, & Nakagawa K. Steep elevation of blood interleukin-6 (IL-6) associated only with late stages of cachexia in cancer patients. Eur. Cytokine News. 15(4), 312-316 (2004).
53. Shord S.S, et al. Cytochrome P450 2C9 mediated metabolism in people with, and without cancer. Int. J. Clin. Pharmacol. Ther. 46(7), 365-374 (2008).
54. Chien J.Y, Lucksiri A, Ernest C.S, 2nd, Gorski J.C, Wrighton S.A, & Hall S.D. Stochastic prediction of CYP3A-mediated inhibition of midazolam clearance by ketoconazole. Drug Metab. Dispos, 34, 1208-1219 (2006).
55. Gorski J.C, Jones D.R, Haehner-Daniels B.D, Hamman M.A, O?Mara E.M. Jr, & Hall S.D. The contribution of intestinal, and hepatic CYP3A to the interaction between midazolam, and clarithromycin. Clin. Pharmacol. Ther. 64, 133-143 (1998).
56. Bj€orkman S. Prediction of drug disposition in infants, and children by means of physiologically based pharmacokinetic (PBPK) modelling: theophylline, and midazolam as model drugs. Br. J. Clin. Pharmacol. 59(6), 691-704 (2004).
57. Cheeti S, Budha N.R, Rajan S, Dresser M.J, & Jin J.Y. A physiologically-based pharmacokinetic (PBPK) approach to evaluate pharmacokinetics in patients with cancer. Biopharm. Drug Disp. 34(3), 141-154 (2013).
58. Graff J.R, et al. The protein kinase Cb-selective inhibitor, enzastaurin (LY317615.HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer, and glioblastoma grafts. Cancer Res. 65, 7462-7469 (2005).
59. Han B, Dickinson G.L, Turner P.K, & Hall S.D. Prediction of CYP3A Mediated Drug-Drug Interactions: estimation of Gut Wall and Hepatic. ASCPT Annual Meeting, Indianapolis, IN, 2013.
60. Carducci M.A, et al. Phase I dose escalation, and pharmacokinetic study of enzastaurin, an oral protein kinase c beta inhibitor, in patients with advanced cancer. J. Clin. Oncol. 24 (25), 4092-4099 (2006).
61. Welch P.A, Sinha V.P, Cleverly A.L, Darstein C, Flanagan S.D, & Musib L.C. Safety, tolerability, QTc evaluation, and pharmacokinetics of single, and multiple doses of enzastaurin HCl (LY317615), a protein kinase C-b inhibitor, in healthy subjects J. Clin. Pharmacol. 47, 1138-1151 (2007).
62. Kreisl T.N, et al. A phase I trial of enzastaurin in patients with recurrent gliomas. Clin. Cancer Res. 15(10), 3617-3623 (2009).
63. Kyriakis J, & Avruch J. Mammalian mitogen-Activated protein kinase signal transduction pathway activated by stress, and inflammation. Physiol. Rev. 81, 809-869 (2001).
64. Goldstein D.M, Kuglstatter A, Lou Y, & Soth M.J. Selective p38alpha inhibitors clinically evaluated for the treatment of chronic inflammatory disorders. J. Med. Chem. 53, 2345-2353 (2010).
65. Yong H, Koh M, & Moon A. The p38 MAPK inhibitors for the treatment of inflammatory, and cancer. Expert Opin. Investig. Drugs 18(12), 1893-1905 (2009).
66. Lim M.Y, et al. p38 Inhibition attenuates the pro-inflammatory response to C-reactive protein by human peripheral blood mononuclear cells. J. Mol. Cell. Cardiol. 37, 1111-1114 (2004).