Skip to main content
SpringerLink
Log in

Pharmacokinetic Studies in Early Anticancer Drug Development

  • Chapter
  • First Online:
Principles of Anticancer Drug Development

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The last two decades has seen a substantial change in the approaches to the clinical development of anticancer drugs. This paradigm shift was instigated by the discovery of a significant number of highly innovative and distinct classes of molecules in terms of both mechanism of action and chemical structure, along with the deployment of an array of new approaches to clinical trial design. Moreover, a rising understanding of the relationships between pharmacokinetics and pharmacodynamics has encouraged a more systematic and rigorous analysis of the potential role of clinical pharmacology in the day-to-day management of cancer patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Assael BM (1982) Pharmacokinetics and drug distribution during postnatal development. Pharmacol Ther 18:159-197.

    Article  PubMed  CAS  Google Scholar 

  2. Baker SD and Hu S (2009) Pharmacokinetic considerations for new targeted therapies. Clin Pharmacol Ther 85:208-211.

    Article  PubMed  CAS  Google Scholar 

  3. Baker SD, Verweij J, Rowinsky EK, Donehower RC, Schellens JH, Grochow LB and Sparreboom A (2002) Role of body surface area in dosing of investigational anticancer agents in adults, 1991-2001. J Natl Cancer Inst 94:1883-1888.

    Article  PubMed  CAS  Google Scholar 

  4. Bartelink IH, Rademaker CM, Schobben AF and van den Anker JN (2006) Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations. Clin Pharmacokinet 45:1077-1097.

    Article  PubMed  CAS  Google Scholar 

  5. Blanchet B, Billemont B, Cramard J, Benichou AS, Chhun S, Harcouet L, Ropert S, Dauphin A, Goldwasser F and Tod M (2009) Validation of an HPLC-UV method for sorafenib determination in human plasma and application to cancer patients in routine clinical practice. J Pharm Biomed Anal 49:1109-1114.

    Article  PubMed  CAS  Google Scholar 

  6. Blasdel C, Egorin MJ, Lagattuta TF, Druker BJ and Deininger MW (2007) Therapeutic drug monitoring in CML patients on imatinib. Blood 110:1699-1701; author reply 1701.

    Google Scholar 

  7. Bruno R, Hille D, Riva A, Vivier N, ten Bokkel Huinnink WW, van Oosterom AT, Kaye SB, Verweij J, Fossella FV, Valero V, Rigas JR, Seidman AD, Chevallier B, Fumoleau P, Burris HA, Ravdin PM and Sheiner LB (1998) Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer. J Clin Oncol 16:187-196.

    PubMed  CAS  Google Scholar 

  8. Calvert AH, Newell DR, Gumbrell LA, O’Reilly S, Burnell M, Boxall FE, Siddik ZH, Judson IR, Gore ME and Wiltshaw E (1989) Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7:1748-1756.

    PubMed  CAS  Google Scholar 

  9. Canal P, Chatelut E and Guichard S (1998) Practical treatment guide for dose individualisation in cancer chemotherapy. Drugs 56:1019-1038.

    Article  PubMed  CAS  Google Scholar 

  10. Charles KA, Rivory LP, Brown SL, Liddle C, Clarke SJ and Robertson GR (2006) Transcriptional repression of hepatic cytochrome P450 3A4 gene in the presence of cancer. Clin Cancer Res 12:7492-7497.

    Article  PubMed  CAS  Google Scholar 

  11. Chatelut E, Canal P, Brunner V, Chevreau C, Pujol A, Boneu A, Roche H, Houin G and Bugat R (1995) Prediction of carboplatin clearance from standard morphological and biological patient characteristics. J Natl Cancer Inst 87:573-580.

    Article  PubMed  CAS  Google Scholar 

  12. Collins JM, Zaharko DS, Dedrick RL and Chabner BA (1986) Potential roles for preclinical pharmacology in phase I clinical trials. Cancer Treat Rep 70:73-80.

    PubMed  CAS  Google Scholar 

  13. Cox MC, Low J, Lee J, Walshe J, Denduluri N, Berman A, Permenter MG, Petros WP, Price DK, Figg WD, Sparreboom A and Swain SM (2006) Influence of garlic (Allium sativum) on the pharmacokinetics of docetaxel. Clin Cancer Res 12:4636-4640.

    Article  PubMed  CAS  Google Scholar 

  14. Cusatis G, Gregorc V, Li J, Spreafico A, Ingersoll RG, Verweij J, Ludovini V, Villa E, Hidalgo M, Sparreboom A and Baker SD (2006) Pharmacogenetics of ABCG2 and adverse reactions to gefitinib. J Natl Cancer Inst 98:1739-1742.

    Article  PubMed  CAS  Google Scholar 

  15. DeMario MD and Ratain MJ (1998) Oral chemotherapy: rationale and future directions. J Clin Oncol 16:2557-2567.

    PubMed  CAS  Google Scholar 

  16. Dooley MJ and Poole SG (2000) Poor correlation between body surface area and glomerular filtration rate. Cancer Chemother Pharmacol 46:523-526.

    Article  PubMed  CAS  Google Scholar 

  17. Dy GK, Bekele L, Hanson LJ, Furth A, Mandrekar S, Sloan JA and Adjei AA (2004) Complementary and alternative medicine use by patients enrolled onto phase I clinical trials. J Clin Oncol 22:4810-4815.

    Article  PubMed  Google Scholar 

  18. Egorin MJ, Van Echo DA, Olman EA, Whitacre MY, Forrest A and Aisner J (1985) Prospective validation of a pharmacologically based dosing scheme for the cisdiamminedichloroplatinum(II) analogue diamminecyclobutanedicarboxylatoplatinum. Cancer Res 45:6502-6506.

    PubMed  CAS  Google Scholar 

  19. Eisenhauer EA, O’Dwyer PJ, Christian M and Humphrey JS (2000) Phase I clinical trial design in cancer drug development. J Clin Oncol 18:684-692.

    PubMed  CAS  Google Scholar 

  20. Evans WE and McLeod HL (2003) Pharmacogenomics--drug disposition, drug targets, and side effects. N Engl J Med 348:538-549.

    Article  PubMed  CAS  Google Scholar 

  21. Evans WE, Relling MV, Rodman JH, Crom WR, Boyett JM and Pui CH (1998) Conventional compared with individualized chemotherapy for childhood acute lymphoblastic leukemia. N Engl J Med 338:499-505.

    Article  PubMed  CAS  Google Scholar 

  22. Evans WE, Rodman JH, Relling MV, Crom WR, Rivera GK, Pratt CB and Crist WM (1991) Concept of maximum tolerated systemic exposure and its application to phase I-II studies of anticancer drugs. Med Pediatr Oncol 19:153-159.

    Article  PubMed  CAS  Google Scholar 

  23. Evans WE, Rodman JH, Relling MV, Petros WP, Stewart CF, Pui CH and Rivera GK (1992) Differences in teniposide disposition and pharmacodynamics in patients with newly diagnosed and relapsed acute lymphocytic leukemia. J Pharmacol Exp Ther 260:71-77.

    PubMed  CAS  Google Scholar 

  24. Felici A, Verweij J and Sparreboom A (2002) Dosing strategies for anticancer drugs: the good, the bad and body-surface area. Eur J Cancer 38:1677-1684.

    Article  PubMed  CAS  Google Scholar 

  25. Gallo JM, Laub PB, Rowinsky EK, Grochow LB and Baker SD (2000) Population pharmacokinetic model for topotecan derived from phase I clinical trials. J Clin Oncol 18:2459-2467.

    PubMed  CAS  Google Scholar 

  26. Gardner ER, Burger H, van Schaik RH, van Oosterom AT, de Bruijn EA, Guetens G, Prenen H, De Jong FA, Baker SD, Bates SE, Figg WD, Verweij J, Sparreboom A and Nooter K (2006) Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib. Clin Pharmacol Ther 80:192-201.

    Article  PubMed  CAS  Google Scholar 

  27. Gibbons J, Egorin MJ, Ramanathan RK, Fu P, Mulkerin DL, Shibata S, Takimoto CH, Mani S, LoRusso PA, Grem JL, Pavlick A, Lenz HJ, Flick SM, Reynolds S, Lagattuta TF, Parise RA, Wang Y, Murgo AJ, Ivy SP and Remick SC (2008) Phase I and pharmacokinetic study of imatinib mesylate in patients with advanced malignancies and varying degrees of renal dysfunction: a study by the National Cancer Institute Organ Dysfunction Working Group. J Clin Oncol 26:570-576.

    Article  PubMed  CAS  Google Scholar 

  28. Grandison MK and Boudinot FD (2000) Age-related changes in protein binding of drugs: implications for therapy. Clin Pharmacokinet 38:271-290.

    Article  PubMed  CAS  Google Scholar 

  29. Gretz N, Schock D, Sadick M and Pill J (2007) Bias and precision of estimated glomerular filtration rate in children. Pediatr Nephrol 22:167-169.

    Article  PubMed  Google Scholar 

  30. Gurney H (1996) Dose calculation of anticancer drugs: a review of the current practice and introduction of an alternative. J Clin Oncol 14:2590-2611.

    PubMed  CAS  Google Scholar 

  31. Hainsworth JD (1999) Extended-schedule oral etoposide in selected neoplasms and overview of administration and scheduling issues. Drugs 58 Suppl 3:51-56.

    Article  PubMed  CAS  Google Scholar 

  32. Hooker AC, Ten Tije AJ, Carducci MA, Weber J, Garrett-Mayer E, Gelderblom H, McGuire WP, Verweij J, Karlsson MO and Baker SD (2008) Population pharmacokinetic model for docetaxel in patients with varying degrees of liver function: incorporating cytochrome P4503A activity measurements. Clin Pharmacol Ther 84:111-118.

    Article  PubMed  CAS  Google Scholar 

  33. Huang RS and Ratain MJ (2009) Pharmacogenetics and pharmacogenomics of anticancer agents. CA Cancer J Clin 59:42-55.

    Article  PubMed  Google Scholar 

  34. Huang SM, Temple R, Xiao S, Zhang L and Lesko LJ (2009) When to conduct a renal impairment study during drug development: US Food and Drug Administration perspective. Clin Pharmacol Ther 86:475-479.

    Article  PubMed  CAS  Google Scholar 

  35. Jaquenoud SE, van dV, Rentsch K, Eap CB and Baumann P (2006) Therapeutic drug monitoring and pharmacogenetic tests as tools in pharmacovigilance. Drug Saf 29:735-768.

    Google Scholar 

  36. Kim DH, Sriharsha L, Xu W, Kamel-Reid S, Liu X, Siminovitch K, Messner HA and Lipton JH (2009) Clinical relevance of a pharmacogenetic approach using multiple candidate genes to predict response and resistance to imatinib therapy in chronic myeloid leukemia. Clin Cancer Res 15:4750-4758.

    Article  PubMed  CAS  Google Scholar 

  37. Kim RB (2003) Organic anion-transporting polypeptide (OATP) transporter family and drug disposition. Eur J Clin Invest 33 Suppl 2:1-5.

    Article  PubMed  Google Scholar 

  38. Kola I and Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3:711-715.

    Article  PubMed  CAS  Google Scholar 

  39. Larson RA, Druker BJ, Guilhot F, O’Brien SG, Riviere GJ, Krahnke T, Gathmann I and Wang Y (2008) Imatinib pharmacokinetics and its correlation with response and safety in chronicphase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood 111:4022-4028.

    Article  PubMed  CAS  Google Scholar 

  40. Lazarou J, Pomeranz BH and Corey PN (1998) Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. J Am Med Assoc 279:1200-1205.

    Article  CAS  Google Scholar 

  41. Li J, Karlsson MO, Brahmer J, Spitz A, Zhao M, Hidalgo M and Baker SD (2006) CYP3A phenotyping approach to predict systemic exposure to EGFR tyrosine kinase inhibitors. J Natl Cancer Inst 98:1714-1723.

    Article  PubMed  CAS  Google Scholar 

  42. Lu JF, Eppler SM, Wolf J, Hamilton M, Rakhit A, Bruno R and Lum BL (2006) Clinical pharmacokinetics of erlotinib in patients with solid tumors and exposure-safety relationship in patients with non-small cell lung cancer. Clin Pharmacol Ther 80:136-145.

    Article  PubMed  CAS  Google Scholar 

  43. Mahmood I and Balian JD (1999) The pharmacokinetic principles behind scaling from preclinical results to phase I protocols. Clin Pharmacokinet 36:1-11.

    Article  PubMed  CAS  Google Scholar 

  44. Mathijssen RH and Sparreboom A (2009) Influence of lean body weight on anticancer drug clearance. Clin Pharmacol Ther 85:23; author reply 24.

    Google Scholar 

  45. Mathijssen RH, Verweij J, De Bruijn P, Loos WJ and Sparreboom A (2002) Effects of St. John’s wort on irinotecan metabolism. J Natl Cancer Inst 94:1247-1249.

    Article  CAS  Google Scholar 

  46. McLean TW and Kemper KJ (2006) Complementary and alternative medicine therapies in pediatric oncology patients. J Soc Integr Oncol 4:40-45.

    PubMed  Google Scholar 

  47. McLeod HL, Relling MV, Crom WR, Silverstein K, Groom S, Rodman JH, Rivera GK, Crist WM and Evans WE (1992) Disposition of antineoplastic agents in the very young child. Br J Cancer Suppl 18:S23-S29.

    PubMed  CAS  Google Scholar 

  48. Milsap RL and Jusko WJ (1994) Pharmacokinetics in the infant. Environ Health Perspect 102 Suppl 11:107-110.

    Article  PubMed  Google Scholar 

  49. Moore MM, Chua W, Charles KA and Clarke SJ (2010) Inflammation and cancer: causes and consequences. Clin Pharmacol Ther 87:504-508.

    Article  PubMed  CAS  Google Scholar 

  50. Newell DR, Burtles SS, Fox BW, Jodrell DI and Connors TA (1999) Evaluation of rodent-only toxicology for early clinical trials with novel cancer therapeutics. Br J Cancer 81:760-768.

    Article  PubMed  CAS  Google Scholar 

  51. Perdaems N, Bachaud JM, Rouzaud P, Murris-Espin M, Hermant C, Mihura J, Lochon I, Houin G, Canal P and Chatelut E (1998) Relation between unbound plasma concentrations and toxicity in a prolonged oral etoposide schedule. Eur J Clin Pharmacol 54:677-683.

    Article  PubMed  CAS  Google Scholar 

  52. Picard S, Titier K, Etienne G, Teilhet E, Ducint D, Bernard MA, Lassalle R, Marit G, Reiffers J, Begaud B, Moore N, Molimard M and Mahon FX (2007) Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood 109:3496-3499.

    Article  PubMed  CAS  Google Scholar 

  53. Pinkel D (1958) The use of body surface area as a criterion of drug dosage in cancer chemotherapy. Cancer Res 18:853-856.

    PubMed  CAS  Google Scholar 

  54. Powis G, Harris RN, Basseches PJ and Santone KS (1986) Effects of advanced leukemia on hepatic drug-metabolizing activity in the mouse. Cancer Chemother Pharmacol 16:43-49.

    Article  PubMed  CAS  Google Scholar 

  55. Relling MV, Crom WR, Pieper JA, Cupit GC, Rivera GK and Evans WE (1987) Hepatic drug clearance in children with leukemia: changes in clearance of model substrates during remission-induction therapy. Clin Pharmacol Ther 41:651-660.

    Article  PubMed  CAS  Google Scholar 

  56. Rodman JH, Maneval DC, Magill HL and Sunderland M (1993) Measurement of Tc-99m DTPA serum clearance for estimating glomerular filtration rate in children with cancer. Pharmacother 13:10-16.

    CAS  Google Scholar 

  57. Slevin ML, Clark PI, Joel SP, Malik S, Osborne RJ, Gregory WM, Lowe DG, Reznek RH and Wrigley PF (1989) A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer. J Clin Oncol 7:1333-1340.

    PubMed  CAS  Google Scholar 

  58. Smith NF, Figg WD and Sparreboom A (2005) Role of the liver-specific transporters OATP1B1 and OATP1B3 in governing drug elimination. Expert Opin Drug Metab Toxicol 1:429-445.

    Article  PubMed  CAS  Google Scholar 

  59. Sparreboom A, Chen H, Acharya MR, Senderowicz AM, Messmann RA, Kuwabara T, Venzon DJ, Murgo AJ, Headlee D, Sausville EA and Figg WD (2004) Effects of alpha1-acid glycoprotein on the clinical pharmacokinetics of 7-hydroxystaurosporine. Clin Cancer Res 10:6840-6846.

    Article  PubMed  CAS  Google Scholar 

  60. Sparreboom A, Cox MC, Acharya MR and Figg WD (2004) Herbal remedies in the United States: potential adverse interactions with anticancer agents. J Clin Oncol 22:2489-2503.

    Article  PubMed  CAS  Google Scholar 

  61. Sparreboom A, Danesi R, Ando Y, Chan J and Figg WD (2003) Pharmacogenomics of ABC transporters and its role in cancer chemotherapy. Drug Resist Updat 6:71-84.

    Article  PubMed  CAS  Google Scholar 

  62. Sparreboom A, Nooter K, Loos WJ and Verweij J (2001) The (ir)relevance of plasma protein binding of anticancer drugs. Neth J Med 59:196-207.

    Article  PubMed  CAS  Google Scholar 

  63. Sparreboom A, van AJ, Mayer U, Schinkel AH, Smit JW, Meijer DK, Borst P, Nooijen WJ, Beijnen JH and van TO (1997) Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci USA 94:2031-2035.

    Google Scholar 

  64. Sparreboom A, van ZL, Brouwer E, Loos WJ, de BP, Gelderblom H, Pillay M, Nooter K, Stoter G and Verweij J (1999) Cremophor EL-mediated alteration of paclitaxel distribution in human blood: clinical pharmacokinetic implications. Cancer Res 59:1454-1457.

    Google Scholar 

  65. Sparreboom A and Verweij J (2009) Advances in cancer therapeutics. Clin Pharmacol Ther 85:113-117.

    Article  PubMed  CAS  Google Scholar 

  66. Sparreboom A, Wolff AC, Mathijssen RH, Chatelut E, Rowinsky EK, Verweij J and Baker SD (2007) Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese. J Clin Oncol 25:4707-4713.

    Article  PubMed  CAS  Google Scholar 

  67. Strolin BM, Whomsley R and Baltes EL (2005) Differences in absorption, distribution, metabolism and excretion of xenobiotics between the paediatric and adult populations. Expert Opin Drug Metab Toxicol 1:447-471.

    Article  Google Scholar 

  68. Tannock IF, Boyd NF, DeBoer G, Erlichman C, Fine S, Larocque G, Mayers C, Perrault D and Sutherland H (1988) A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer. J Clin Oncol 6:1377-1387.

    PubMed  CAS  Google Scholar 

  69. Tetelbaum M, Finkelstein Y, Nava-Ocampo AA and Koren G (2005) Back to basics: understanding drugs in children: pharmacokinetic maturation. Pediatr Rev 26:321-328.

    Article  PubMed  Google Scholar 

  70. Twelves C, Glynne-Jones R, Cassidy J, Schuller J, Goggin T, Roos B, Banken L, Utoh M, Weidekamm E and Reigner B (1999) Effect of hepatic dysfunction due to liver metastases on the pharmacokinetics of capecitabine and its metabolites. ClinCancer Res 5:1696-1702.

    CAS  Google Scholar 

  71. van Erp NP, Baker SD, Zhao M, Rudek MA, Guchelaar HJ, Nortier JW, Sparreboom A and Gelderblom H (2005) Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. Clin Cancer Res 11:7800-7806.

    Article  PubMed  Google Scholar 

  72. Woo MH, Relling MV, Sonnichsen DS, Rivera GK, Pratt CB, Pui CH, Evans WE and Pappo AS (1999) Phase I targeted systemic exposure study of paclitaxel in children with refractory acute leukemias. Clin Cancer Res 5:543-549.

    PubMed  CAS  Google Scholar 

  73. Zhang Y, Zhang L, Abraham S, Apparaju S, Wu TC, Strong JM, Xiao S, Atkinson AJ, Jr., Thummel KE, Leeder JS, Lee C, Burckart GJ, Lesko LJ and Huang SM (2009) Assessment of the impact of renal impairment on systemic exposure of new molecular entities: evaluation of recent new drug applications. Clin Pharmacol Ther 85:305-311.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, CCC Room I5308, Mail Stop 313, Memphis, TN, 38105-3678, USA

    Sharyn D. Baker

Authors
  1. Alex Sparreboom
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharyn D. Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sharyn D. Baker .

Editor information

Editors and Affiliations

  1. Dept. Biostatistics, Bioinformatics &, Epidemiology, Medical University of South Carolina, Jonathan Lucas St. 86, Charleston, 29466, South Carolina, USA

    Elizabeth Garrett-Mayer

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Sparreboom, A., Baker, S.D. (2011). Pharmacokinetic Studies in Early Anticancer Drug Development. In: Garrett-Mayer, E. (eds) Principles of Anticancer Drug Development. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7358-0_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-7358-0_8

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4419-7357-3

  • Online ISBN: 978-1-4419-7358-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation