Anticancer Clinical Pharmacology Overview

  • Uday B. Dandamudi
  • Andrew Beelen
  • Lionel D. Lewis
Part of the Cancer Drug Discovery and Development book series (CDD&D)


This chapter is an overview of the principles of clinical pharmacology with a focus on oncology therapeutics. It covers the basic pharmacologic principles of pharmacokinetics and pharmacodynamics which underpin the individualization of a patient’s drug therapy and focuses on the utilization of these principles in anticancer drug therapy prescribing while addressing some of the most recent advances in the field. A unique aspect of this chapter is the intention to bridge the gap between clinical pharmacologists and subspecialty oncologists. This chapter showcases the rationale as to why the discipline of clinical pharmacology plays an increasingly significant role in clinical therapeutics (prescribing) in all specialties where drugs are used to treat disease.


Anti-cancer therapeutics principles Pharmacokinetics Pharmacodynamics 


  1. 1.
    Ross EM, Kenakin TP (2001) Pharmacodynamics: mechanisms of drug action and the relationship between drug concentration and effect. In: Hardman JG, Limbird LE (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 10th edn. McGraw-Hill, New York, NY, pp 31–43Google Scholar
  2. 2.
    Nies AS (2001) Principles of therapeutics. In: Hardman JG, Limbird LE (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 10th edn. McGraw-Hill, New York, NY, pp 45–66Google Scholar
  3. 3.
    Lowe ES, Balis FM (2007) Dose-effect and concentration-effect analysis. In: Atkinson AJ, Abernethy DR, Daniels CE, Dedrick RL, Markey SP (eds) Principles of clinical pharmacology. Academic, Boston, pp 289–299CrossRefGoogle Scholar
  4. 4.
    Ritter JM, Lewis LD, Mant TGK, Ferro A (2008) A textbook of clinical pharmacology, 5th edn. Arnold, London, pp 6–85Google Scholar
  5. 5.
    Atkinson AJ (2001) Kinetic analysis of pharmacologic effect. In: Atkinson AJ, Daniels CE, Dedrick RL, Grudzinskas CV, Markey SP (eds) Principles of clinical pharmacology. Academic, Boston, pp 245–252Google Scholar
  6. 6.
    Nierenberg DW, Melmon KL (2000) Introduction to clinical pharmacology and rational therapeutics. In: Carruthers GS, Hoffman BB, Melmon KL, Nierenberg DW (eds) Melmon and Morrelli’s clinical pharmacology, 4th edn. McGraw-Hill, New York, pp 3–62Google Scholar
  7. 7.
    Kenakin TP, Bond RA, Bonner TI (1992) Definition of pharmacological receptors. Pharmacol Rev 44:351–362PubMedGoogle Scholar
  8. 8.
    Christopoulos A, Kenakin T (2002) G Protein-coupled receptor allosterism and complexing. Pharmacol Rev 54:323–374PubMedCrossRefGoogle Scholar
  9. 9.
    Capdeville R, Buchdunger E, Zimmermann J, Matter A (2002) Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat Rev Drug Discov 1:493–502PubMedCrossRefGoogle Scholar
  10. 10.
    Druker BJ, Talpaz M, Resta DJ et al (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344:1031–1037PubMedCrossRefGoogle Scholar
  11. 11.
    Van Oosterom AT, Judson I, Verweij J et al (2001) Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet 358:1421–1423PubMedCrossRefGoogle Scholar
  12. 12.
    Smith PF, DiCenzo R, Morse GD (2001) Clinical pharmacokinetics of non-nucleoside reverse transcriptase inhibitors. Clin Pharmacokinet 40:893–905PubMedCrossRefGoogle Scholar
  13. 13.
    Macgregor JI, Jordan VC (1998) Basic guide to the mechanisms of antiestrogen action. Pharmacol Rev 50:151–196PubMedGoogle Scholar
  14. 14.
    Caponigro F, French RC, Kaye SB (1997) Protein kinase C: a worthwhile target for anticancer drugs? Anticancer Drugs 8:26–33PubMedCrossRefGoogle Scholar
  15. 15.
    Buxton IL (2006) Pharmacokinetics: the dynamics of drug absorption, distribution, and elimination. In: Burnton LL, Lazo SL, Parker KL (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 10th edn. McGraw-Hill, New York, NYGoogle Scholar
  16. 16.
    Boroujerdi M (2002) Pharmacokinetics: principles and applications. McGraw-Hill, New York, NY, pp 343–367Google Scholar
  17. 17.
    Shargel L, Yu ABC (1999) Applied biopharmaceutics and pharmacokinetics, 4th edn. Appleton & Lange, Norwalk, CT, pp 573–605Google Scholar
  18. 18.
    Borst P, Elferink RO (2002) Mammalian abc transporters in health and disease. Annu Rev Biochem 71:537–592PubMedCrossRefGoogle Scholar
  19. 19.
    Gottesman MM, Fojo T, Bates SE (2002) Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer 2:48–58PubMedCrossRefGoogle Scholar
  20. 20.
    Jamieson GP, Snook MB, Bradley TR et al (1989) Transport and metabolism of 1-beta-D-arabinofuranosylcytosine in human ovarian adenocarcinoma cells. Cancer Res 49:309–313PubMedGoogle Scholar
  21. 21.
    Mackey JR, Yao SY, Smith KM et al (1999) Gemcitabine transport in Xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst 91:1876–1881PubMedCrossRefGoogle Scholar
  22. 22.
    Moscow JA (1998) Methotrexate transport and resistance. Leuk Lymphoma 30:215–224PubMedGoogle Scholar
  23. 23.
    Kalman S, Metcalf K, Eintrei C (1997) Morphine, morphine-6-glucuronide, and morphine-3-glucuronide in cerebrospinal fluid and plasma after epidural administration of morphine. Reg Anesth 22:131–136PubMedCrossRefGoogle Scholar
  24. 24.
    Goetz MP, Knox SK, Suman VJ, Rae JM, Safgren SL et al (2007) The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat 101(1):113–121PubMedCrossRefGoogle Scholar
  25. 25.
    Schorth W, Goetz MP, Hamann U, Fasching PA et al (2009) Association between CYP2D6 polymorphisms and outcomes among women with early stage cancer treated with tamoxifen. JAMA 302(13):1429–1436CrossRefGoogle Scholar
  26. 26.
    Innocenti F, Iyer L, Ratain MJ (2001) Pharmacogenetics of anticancer agents: lessons from amonafide and irinotecan. Drug MetabDispos 29:596–600Google Scholar
  27. 27.
    Bachmann KA, Belloto RJ Jr (1999) Differential kinetics of phenytoin in elderly patients. Drugs Aging 15:235–250PubMedCrossRefGoogle Scholar
  28. 28.
    Bruno R, Vivier N, Veyrat-Follet C, Montay G, Rhodes GR (2001) Population pharmacokinetics and pharmacokinetic–pharmacodynamic relationships for docetaxel. Invest New Drugs 19:163–169PubMedCrossRefGoogle Scholar
  29. 29.
    Meibohm B, Derendorf H (1997) Basic concepts of pharmacokinetic/pharmacodynamic (PK/PD) modelling. Int J Clinpharmacol Ther 35:401–413Google Scholar
  30. 30.
    Sekine I, Saijo N (2001) Polymorphisms of metabolizing enzymes and transporter proteins involved in the clearance of anticancer agents. Ann Oncol 12:1515–1525PubMedCrossRefGoogle Scholar
  31. 31.
    Roden DM, George AL Jr (2002) The genetic basis of variability in drug responses. Nat Rev Drug Discov 1:37–44PubMedCrossRefGoogle Scholar
  32. 32.
    Evans WE, Johnson JA (2001) Pharmacogenomics: the inherited basis for interindividual differences in drug response. Annu Rev Genom Hum Genet 2:9–39CrossRefGoogle Scholar
  33. 33.
    Nolin TD (2008) Altered nonrenal drug clearance in ESRD. CurrOpinNephrolHypertens 17(6):555–559Google Scholar
  34. 34.
    Frye RF, Fitzgerald SM et al (2004) Effect of St John’s wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 76(4):323–329PubMedCrossRefGoogle Scholar
  35. 35.
    Mathijssen RH, Verweij J, de Bruijn P et al (2002) Effects of St. John’s wort on irinotecan metabolism. J Natl Cancer Inst 91(16):1247–1249CrossRefGoogle Scholar
  36. 36.
    Lotsch J, Skarke C, Grosch S, Darimont J, Schmidt H, Geisslinger G (2002) The polymorphism A118G of the human mu-opioid receptor gene decreases the pupil constrictory effect of morphine-6-glucuronide but not that of morphine. Pharmacogenetics 12:3–9PubMedCrossRefGoogle Scholar
  37. 37.
    Monzo M, Rosell R, Sanchez JJ et al (1999) Paclitaxel resistance in non-small-cell lung cancer associated with beta-tubulin gene mutations. J Clin Oncol 17:1786–1793PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Uday B. Dandamudi
    • 1
  • Andrew Beelen
    • 2
  • Lionel D. Lewis
    • 1
  1. 1.Section of Clinical Pharmacology, Department of MedicineDartmouth-Hitchcock Medical CenterLebanonUSA
  2. 2.Clinical Research, Myriad PharmaceuticalsSalt Lake CityUSA

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