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Drug Interactions and Pharmacogenetics

  • François Lokiec
Chapter

Abstract

Drug interaction in cancer chemotherapy is one of the most common phenomena in cancer treatment. Cancer patients often take several medications at the same time, not only for treating their cancer but also for side effects and other secondary illnesses. The number of comedications increases with age, and drug interactions are critical for elderly patients. Because of this, they can be at high risk for adverse drug interactions and duplicate medications. Consequences of these interactions can range from inactivation of cancer-fighting medications to severe injury or death of the patient. Pharmacogenetics studies the relationship between genetic polymorphisms and individual responses to drugs. In recent years, there has been great progress in our knowledge of the effects of drug-metabolizing enzymes and molecular target genetic polymorphisms on cancer chemotherapy. Pharmacogenetics focuses on the prediction of drug efficacy and toxicity based on a patient’s genetic profile with routinely applicable genetic tests to select the most appropriate medication at optimal doses for each individual patient.

Keywords

Anticancer drugs Drug interactions Pharmacogenetics Pharmacodynamics Pharmacokinetics Cytochromes P450 

References

  1. 1.
    Finley RS. Drug interactions in the oncology patients. Semin Oncol Nurs. 1992;8:95–101.CrossRefPubMedGoogle Scholar
  2. 2.
    Kuhlmann J, Muck W. Clinical-pharmacologic strategies to assess drug interaction potential during drug development. Drug Saf. 2001;24:715–25.CrossRefPubMedGoogle Scholar
  3. 3.
    Balducci L. Pharmacology of antineoplastic medications in older cancer patients. Oncology. 2009;23:78–85.PubMedGoogle Scholar
  4. 4.
    Evans WE, McLeod HL. Pharmacogenomics-drug disposition, drug targets, and side effects. N Engl J Med. 2003;348:538–45.CrossRefPubMedGoogle Scholar
  5. 5.
    Weinshilboum R. Inheritance and drug response. N Engl J Med. 2003;348:529–37.CrossRefPubMedGoogle Scholar
  6. 6.
    Scripture CD, Sparreboom A, Figg WD. Modulation of cytochrome P450 activity: implications for cancer therapy. Lancet Oncol. 2005;6:780–9.CrossRefPubMedGoogle Scholar
  7. 7.
    William DA, Lokich J. A review on the stability and compatibility of antineoplastic drugs for multiple-drug infusions. Cancer Chemother Pharmacol. 1992;31:171–81.CrossRefGoogle Scholar
  8. 8.
    Newton DW. Drug incompatibility chemistry. Am J Health Syst Pharm. 2009;66:348–57.CrossRefPubMedGoogle Scholar
  9. 9.
    Gunnarsson PO, Davidson T, Andersson SB, Backman C, Johansson SA. Impairment estramustine phosphate absorption by concurrent intake of milk and food. Eur J Clin Pharmacol. 1990;38:189–93.CrossRefPubMedGoogle Scholar
  10. 10.
    Reignier B, Verweij J, Dirix L, Cassidy J, Twelves C, Allman D, et al. Effect of food on the pharmacokinetics of capecitabine and its metabolites following oral administration in cancer patients. Clin Cancer Res. 1998;4:941–8.Google Scholar
  11. 11.
    Singh BN, Malhtrota BK. Effects of food on the clinical pharmacokinetics of anticancer agents: underlying mechanisms and implications for oral chemotherapy. Clin Pharmacokinet. 2004;43:1127–56.CrossRefPubMedGoogle Scholar
  12. 12.
    Zhang Y, Benet LZ. The gut as a barrier to drug absorption: combined role of cytochrome P450 3A and P-glycoprotéine. Clin Pharmacokinet. 2001;40:159–68.CrossRefGoogle Scholar
  13. 13.
    Bailey DG, Arnold JM, Spence JD. Grapefruit juice and drugs. Clin Pharmacokinet. 1994;26:91–8.CrossRefPubMedGoogle Scholar
  14. 14.
    He K, Iyer KR, Hayes RN, Sinz MW, Woolf TF, Hollenberg PF. Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice. Chem Res Toxicol. 1998;11:252–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Edwards DJ, Bellevue IIIFH, Woster PM. Identification of 6’,7’-dihydroxybergamottin, a cytochrome P450 inhibitor, in grapefruit juice. Drug Metab Dispos. 1996;24:1287–90.PubMedGoogle Scholar
  16. 16.
    Veronese ML, Gillen LP, Burke JP, Dorval EP, Hauck WW, Pequignot E, et al. Exposure-dependent inhibition of intestinal and hepatic CYP3A4 in vivo by grapefruit juice. J Clin Pharmacol. 2003;43:831–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Liegler DG, Henderson ES, Hahn MA. The effect of organic acids on renal clearance of methotrexate in man. Clin Pharmacol Ther. 1969;10:849–57.CrossRefPubMedGoogle Scholar
  18. 18.
    Mandel MA. The synergistic effect of salicylates on methotrexate toxicity. Plast Reconstr Surg. 1976;57:733–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Maiche AG. Acute renal failure due to concomitant interaction between methotrexate and indomethacin. Lancet. 1986;1:1390.CrossRefPubMedGoogle Scholar
  20. 20.
    Thomas MH, Gutterman LA. Methotrexate toxicity in a patient receiving trimethoprim-sulfamethoxazole. J Rheumatol. 1986;13:440–1.PubMedGoogle Scholar
  21. 21.
    Maricic M, Davis M, Gall EP. Megaloblastic pancytopenia in a patient receiving concurrent methotrexate and trimethoprim-sulfamethoxazole treatment. Arthritis Rheum. 1986;29:133–5.CrossRefPubMedGoogle Scholar
  22. 22.
    Burns JS, Conney AH. Enzyme stimulation and inhibition in the metabolism of drugs. Proc R Soc Med. 1965;58:955–60.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Remmer H. Induction of drug metabolizing enzyme system in the liver. Eur J Clin Pharmacol. 1972;5:116–36.CrossRefGoogle Scholar
  24. 24.
    Solomon HM, Abrams WB. Interactions between digitoxin and other drugs in man. Am Heart J. 1972;83:277–80.CrossRefPubMedGoogle Scholar
  25. 25.
    Vesell ES, Passaniti TC, Greene FE. Impairment of drug metabolism in man by allopurinol and nortriptiline. N Engl J Med. 1970;283:1484–8.CrossRefPubMedGoogle Scholar
  26. 26.
    Kjellen E, Wennerberg J, Pero R. Metoclopramide enhances the effect of cisplatin on xenografted squamous cell carcinoma of the head and neck. Br J Cancer. 1989;59:247–50.CrossRefPubMedGoogle Scholar
  27. 27.
    Henriksson R, Gankvist K. Epirubicin cytotoxicity but not oxygen radical formation is enhanced by four different anti-emetics. Med Oncol Tumor Pharmacother. 1989;59:175–8.Google Scholar
  28. 28.
    Dorr RT, Soble MJ, Alberts DS. Interaction of cimetidine but not ranitidine with cyclophosphamide in mice. Cancer Res. 1986;46:1795–9.PubMedGoogle Scholar
  29. 29.
    Hess WA, Kornblith PL. Combination of lomustine and cimetidine in the treatment of a patient with malignant glioblastoma: a case report. Cancer Treat Rep. 1985;69:733–5.PubMedGoogle Scholar
  30. 30.
    Volkin RL, Shadduck RK, Winkelstein A, Ziegler ZR, Selker RG. Potentiation of carmustine-cranial irradiation induced myelosuppression by cimetidine. Arch Intern Med. 1986;142:243–5.CrossRefGoogle Scholar
  31. 31.
    Thyss A, Milano G, Kubar J, Namer M, Schneider M. Clinical and pharmacokinetic evidence of life-threatening interaction between methotrexate and ketoprofen. Lancet. 1986;1:256–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Ellison NM, Servi RJ. Acute renal failure and death following sequential intermediate-dose methotrexate and 5-FU: a possible adverse effect due to concomitant indomethacin administration. Cancer Treat Rep. 1985;69:342–3.PubMedGoogle Scholar
  33. 33.
    Gaffen JD, Bennett A, Barer MR. A new method for studying cell growth in suspension, and its use to show that indomethacin enhances cell killing by methotrexate. J Pharm Pharmacol. 1985;37:261–3.CrossRefPubMedGoogle Scholar
  34. 34.
    Ogino M, Okinaga S, Kaibara M, Ishiwata I. NSAID indomethacin enhanced cytostatic effect of cisplatinum on the proliferation of prostaglandin-producing and –nonproducing cancers in cell line. In:Eicosanoids and bioactive lipids in cancer and radiation injury. Boston: Springer; 1989.Google Scholar
  35. 35.
    Nierenberg DW. Competitive inhibition of methotrexate accumulation in rabbit kidney slices by non steroidal anti-inflammatory drugs. J Pharmacol Exp Ther. 1983;226:1–6.PubMedGoogle Scholar
  36. 36.
    Kirsch W, Schulz D, Van Burskirk J, Young H. Effects of sodium warfarin and other cariostatic agents on malignant cells: a study of drug synergy. J Med. 1974;5:69–82.PubMedGoogle Scholar
  37. 37.
    Clarke GD, Ryan PJ. Tranquilizers can block mitogenesis in 3T3 cells and induce differentiation in Friend cells. Nature. 1980;287:160–1.CrossRefPubMedGoogle Scholar
  38. 38.
    Feif C. Diazepam induces mitotic arrest at prometaphase by inhibiting centrilar separation. Nature. 1981;291:247–8.CrossRefGoogle Scholar
  39. 39.
    Juvekar AS, Chitnis MP, Advani SH. In vitro modulation of Adriamycin and mitoxantrone cytotoxicity by hyperthermia and diazepam in human chronic myeloid leukemia cells. Neoplasma. 1987;34:199–204.PubMedGoogle Scholar
  40. 40.
    Raichle ME, Hartman BK, Eichling JO, Sharpe LG. Central noradrenergic regulation of cerebral blood flow and vascular permeability. Proc Natl Acad Sci. 1975;72:3726–30.CrossRefPubMedGoogle Scholar
  41. 41.
    Nierenberg DW. Toxic reaction to methotrexate in a patient receiving penicillin and furosemide: a possible interaction. Arch Dermatol. 1983;119:449–50.CrossRefPubMedGoogle Scholar
  42. 42.
    Zager R, Frisby S, Oliverio V. The effect of antibiotics and cancer chemotherapeutic agents in the cellular transport and antitumor activity of methotrexate in L1210 murine leukemia. Cancer Res. 1973;33:1670–6.PubMedGoogle Scholar
  43. 43.
    Osieka R, Glatte P, Pannenbäcker R, Schmitt CG. Enhancement of semustine-induced cytotoxicity by chlorpromazine and caffeine in a human melanoma xenograft. Cancer Treat Rep. 1986;70:1167–71.PubMedGoogle Scholar
  44. 44.
    Cohen MH, Schoenfeld D, Wolter J. Randomized trial of chlorpromazine, caffeine and methyl-CCNU in disseminated melanoma. Cancer Treat Rep. 1980;64:151–3.PubMedGoogle Scholar
  45. 45.
    Goddard PM, Jones M, Pollard LA, Valenti MR, Harrap KR. The 5-HT3 antagonist BRL 43694, does not compromise the efficacy of cisplatin in tumour-bearing mice. Cancer Chemother Pharmacol. 1991;25:377–9.CrossRefGoogle Scholar
  46. 46.
    Hall TJ, Cambridge G, James PR. Development of a co-culture system with induced HEPG2 cells and K562 cells for examining drug metabolism in vitro. Studies with cyclophosphamide, ondansetron and cisplatin. Res Commun Chem Pathol Pharmacol. 1991;72:161–8.PubMedGoogle Scholar
  47. 47.
    Hande K, Combs G, Swingle R, Combs GL, Anthony L. Effects of cimetidine and ranitidine on the metabolism and toxicity of hexamethylmelamine. Cancer Treat Rep. 1986;70:1443–5.PubMedGoogle Scholar
  48. 48.
    Alberts DS, Mason-Liddil N, Plezia PM, Roe DL, Dorr RT, Struck RF, et al. Lack of ranitidine effects on cyclophosphamide bone marrow toxicity or metabolism: a placebo-controlled clinical trial. J Natl Cancer Inst. 1991;83:1739–43.CrossRefPubMedGoogle Scholar
  49. 49.
    Harvey VJ, Slevin ML, Dilloway MR. The influence of cimetidine on the pharmacokinetics of 5-fluorouracil. Br J Clin Pharmacol. 1984;18:421–30.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Brenner DE, Collins JC, Hande KR. The effects of cimetidine upon the plasma pharmacokinetics of doxorubicin in rabbits. Cancer Chemother Pharmacol. 1986;18:219–22.CrossRefPubMedGoogle Scholar
  51. 51.
    Dorr RT, Alberts DS. Cimetidine enhancement of cyclophosphamide antitumor activity. Br J Cancer. 1982;45:35–43.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Singh RR, Malaviya AN, Pandey JN, Guleria JS. Fatal interaction between methotrexate and naproxen. Lancet. 1986;1:1390.CrossRefPubMedGoogle Scholar
  53. 53.
    Goldenberg GJ. Drug-induced stimulation of nitrogen mustard and choline transport and other system in L5178Y lymphoblasts. Cancer Res. 1974;34:2511–6.PubMedGoogle Scholar
  54. 54.
    Goldenberg GJ. Drug-induced stimulation of nitrogen mustard and choline by normal and leukemic human cells in vitro. Cancer Res. 1976;36:978–82.PubMedGoogle Scholar
  55. 55.
    Gieringer JH, Wenz AF, Just HM, Daschner FD. Effect of 5-fluorouracil, mitoxantrone, methotrexate, and vincristine on the bacterial activity of ceftriaxone, ceftazidime, cefotiam, piperacillin, and netilmicin. Chemotherapy. 1986;32:418–24.CrossRefPubMedGoogle Scholar
  56. 56.
    Spector GN, Gleiser CA, Chan RC, Van Eys J. Effects of gentamicin and irradiation of the toxicity of high-dose methotrexate in rats. Cancer Treat Rep. 1980;64:989–91.PubMedGoogle Scholar
  57. 57.
    Valeriote F, Medoff G, Dieckman J. Potentiation of anticancer cytotoxicity against sensitive and resistant AKR leukemia by amphotericin B1. Cancer Res. 1979;39:2041–5.PubMedGoogle Scholar
  58. 58.
    Present C, Klahr C, Santala R. Amphotericin B induction sensitivity to Adriamycin, 1,3-bis (2chloroethyl)-nitrosourea (BCNU) plus cyclophosphamide in human neoplasia. Ann Intern Med. 1977;86:47–51.CrossRefGoogle Scholar
  59. 59.
    Keyes SR, Rockwell S, Sartorelli AC. Enhancement of mitomycin C cytotoxicity to hypoxic tumor cells by dicumarol in vivo and in vitro. Cancer Res. 1985;45:213–6.PubMedGoogle Scholar
  60. 60.
    Zacharski LR. Basis for selection of anticoagulant drugs for therapeutic trials in human malignancy. Haemostasis. 1986;16:300–20.PubMedGoogle Scholar
  61. 61.
    Grankvisk K, Berström P, Jonsson Ö, Henriksson R. Pharmacologic interactions with quinoid antitumor drugs. Free Radic Res Commun. 1990;8:383–90.CrossRefGoogle Scholar
  62. 62.
    Di Marco A, Dasdia T, Pastori W. Interaction of calcium ions and cAMP on the cytotoxic effect of doxorubicin. Tumori. 1984;30:217–21.CrossRefGoogle Scholar
  63. 63.
    Sotos GA, Grogan L, Allegra CJ. Preclinical and clinical aspects of biomodulation of 5-fluorouracil. Cancer Treat Rev. 1994;20:11–49.CrossRefPubMedGoogle Scholar
  64. 64.
    Doroshow JH, Newman EM. Fluoropyrimidine biochemical modulation in colon cancer. Pharmacology relevant in both the laboratory and the clinic. J Clin Oncol. 1991;9:365–7.CrossRefPubMedGoogle Scholar
  65. 65.
    Bertino JR, Mini E, Fernandes DJ. Sequential methotrexate and 5-fluorouracil: mechanism of synergy. Semin Oncol. 1983;10:2–5.PubMedGoogle Scholar
  66. 66.
    Damon LE, Cadman E, Benz C. Enhancement of 5-fluorouracil antitumor effects by the prior administration of methotrexate. Pharmacol Ther. 1989;43:155–85.CrossRefPubMedGoogle Scholar
  67. 67.
    Hudes GR, LaCreta F, Walczak J, Tinsley P, Litwin S, Comis RL, et al. Pharmacokinetic study of trimetrexate in combination with cisplatin. Cancer Res. 1991;51:3080–7.PubMedGoogle Scholar
  68. 68.
    Kennedy P, Eisenberg M, Silva H, Krasnow S, Perry D, Ettinger D, et al. Toxicity of carboplatin (CBDCA) in combination with methotrexate (MTX) in patients with metastatic squamous cell carcinoma of the head and neck (SCCHN). Proc ASCO. 1987;6:136.Google Scholar
  69. 69.
    Lum BL, Fisher GA, Brophy NA, Yahanda AM, Adler KM, Kaubish S, et al. Clinical trials of modulation of multidrug resistance. Cancer. 1993;72:3503–14.CrossRefGoogle Scholar
  70. 70.
    Boddy A, Idle J. The role of pharmacogenetics in chemotherapy: modulation of tumor response and host toxicity. Cancer Surv. 1993;17:79–104.PubMedGoogle Scholar
  71. 71.
    Rioux PP. Clinical trials in pharmacogenetics and pharmacogenomics: methods and applications. Am J Health Syst Pharm. 2000;57:887–98.PubMedGoogle Scholar
  72. 72.
    Moridani M, Maitland-van der Zee AH, Sasaki H, McKinnon R, Fleckenstein L, Shah VP. AAPS-FIP summary workshop report: pharmacogenetics in individualized medicine: methods, regulatory, and clinical applications. APPS J. 2009;11:214–6.Google Scholar
  73. 73.
    Marsh S, McLeod HL. Cancer pharmacogenetics. Br J Cancer. 2004;90:8–11.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Evans W, Relling M. Pharmacogenomics: translating functional genomics into rational therapeutics. Science. 1999;286:487–91.CrossRefPubMedGoogle Scholar
  75. 75.
    Krynetski E, Evans W. Pharmacogenetics of cancer therapy: getting personal. Am J Hum Genet. 1998;63:11–6.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Vessel E. Advances in pharmacogenetics and pharmacogenomics. J Clin Pharmacol. 2000;40:930–8.CrossRefGoogle Scholar
  77. 77.
    Gupta E, Leistingi TM, Mick R, Ramirez J, Vokes EE, Ratain MJ. Metabolic fate of irinotecan in humans: correlation of glucuronidation with diarrhea. Cancer Res. 1994;54:3723–5.PubMedGoogle Scholar
  78. 78.
    Iyer L, Whitington P, Roy SK, Ratain MJ. Genetic basis for glucuronidation of SN-38: role of UGT*1 isoform. Clin Pharmacol Ther. 1997;61:164.Google Scholar
  79. 79.
    Wasserman E, Myara A, Lokiec F, Goldwasser F, Trivin F, Mahjoubi M, et al. Severe CPT-11 toxicity in patients with Gilbert’s syndrome: two cases report. Ann Oncol. 1997;8:1049–51.CrossRefPubMedGoogle Scholar
  80. 80.
    Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra B, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med. 1995;333:1171–5.CrossRefPubMedGoogle Scholar
  81. 81.
    Köhle C, Möhrle B, Münzel PA, Schwab M, Wernet D, Badary OA, et al. Frequent co-occurrence of the TATA box mutation associated with Gilbert’s syndrome (UGT1A1*28) with other polymorphisms of the UDP-glucuronosyltransferase-1 locus (UGT1A6*2 and UGT1A7*3) in Caucasians and Egyptians. Biochem Pharmacol. 2003;65:1521–7.CrossRefPubMedGoogle Scholar
  82. 82.
    Iyer L, Das S, Janisch L, Wen M, Ramírez J, Karrison T, et al. UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogenomics J. 2002;2:43–7.CrossRefPubMedGoogle Scholar
  83. 83.
    Marcuello E, Altés A, Menoyo A, Del Rio E, Gómez-Pardo M, Baiget M. UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer. Br J Cancer. 2004;9:678–82.CrossRefGoogle Scholar
  84. 84.
    Sachse C, Brockmoller J, Bauer S, Roots L. Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet. 1997;60:284–95.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Goetz MP, Rae JM, Suman VJ, Safgren SL, Ames MM, Visscher DW, et al. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol. 2005;23:9312–8.CrossRefPubMedGoogle Scholar
  86. 86.
    Goetz MP, Knox SK, Suman VJ, Rae JM, Safgren SL, Ames MM, et al. The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat. 2007;101:113–21.CrossRefPubMedGoogle Scholar
  87. 87.
    Hoskins JM, Carey LA, McLeod HL. Cyp2D6 and tamoxifen: DNA matters in breast cancer. Nat Rev Cancer. 2009;9:56–86.CrossRefGoogle Scholar
  88. 88.
    Diasio RB, Harris BE. Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet. 1989;16:215–37.CrossRefPubMedGoogle Scholar
  89. 89.
    Milano G, Etienne MC, Cassuto-Viguier E, Thyss A, Santini J, Fremay M, et al. Influence of sex and age on fluorouracil clearance. J Clin Oncol. 1992;10:1171–5.CrossRefPubMedGoogle Scholar
  90. 90.
    Diasio RB, Lu Z. Dihydropyrimidine dehydrogenase activity and fluorouracil chemotherapy. J Clin Oncol. 1994;12:2239–42.CrossRefPubMedGoogle Scholar
  91. 91.
    Fleming RA, Milano G, Gaspard MH, Bargnoux PJ, Thyss A, Plagne R, et al. Dihydropyrimidine dehydrogenase activity in cancer patients. Eur J Cancer. 1993;29A:740–4.PubMedGoogle Scholar
  92. 92.
    ZH L, Zhang R, Diasio RB. Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy. Cancer Res. 1993;53:5433–8.Google Scholar
  93. 93.
    Albin N, Johnson MR, Diasio RB. cDNA cloning of bovine liver dihydropyrimidine dehydrogenase. DNA Seq. 1996;6:243–50.CrossRefPubMedGoogle Scholar
  94. 94.
    Johnson MR, Wang K, Tillmanns S, Albin N, Diasio RB. Structural organization of the human dihydropyrimidine dehydrogenase gene. Cancer Res. 1997;57:1660–3.PubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • François Lokiec
    • 1
  1. 1.Department of Radio-PharmacologyInstitut Curie, Hôpital René HugueninParisFrance

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