Seminars in Colon & Rectal Surgery
Volume 19, Issue 4 , Pages 226-230 , December 2008

Predictive Factors for Response and Toxicity in Chemotherapy: Pharmacogenomics

  • Hanna K. Sanoff, MD

      Affiliations

    • Department of Medicine, Division of Hematology Oncology, University of North Carolina, Chapel Hill, North Carolina
    • Institute of Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, North Carolina
    • Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina
    • ,
  • Howard L. McLeod, PharmD

      Affiliations

    • Department of Medicine, Division of Hematology Oncology, University of North Carolina, Chapel Hill, North Carolina
    • Institute of Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, North Carolina
    • Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina
    • Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina, Chapel Hill, North Carolina
    • Corresponding Author InformationAddress reprint requests to Howard L. McLeod, PharmD, UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, Campus Box 7360, Kerr Hall, Chapel Hill, NC 27599-7360

References 

  1. Simmonds PC. Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis (Colorectal Cancer Collaborative Group). BMJ. 2000;321(7260):531–535
  2. Gill S, Loprinzi CL, Sargent DJ, et al. Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much?. J Clin Oncol. 2004;22(10):1797–1806
  3. de Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18(16):2938–2947
  4. Saltz LB, Cox JV, Blanke C, et al. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer (Irinotecan Study Group). N Engl J Med. 2000;343(13):905–914
  5. Fuchs CS, Marshall J, Mitchell E, et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007;25(30):4779–4786
  6. Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350(23):2343–2351
  7. Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371(9617):1007–1016
  8. Heggie GD, Sommadossi JP, Cross DS, et al. Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile. Cancer Res. 1987;47(8):2203–2206
  9. Takimoto CH, Lu ZH, Zhang R, et al. Severe neurotoxicity following 5-fluorouracil-based chemotherapy in a patient with dihydropyrimidine dehydrogenase deficiency. Clin Cancer Res. 1996;2(3):477–481
  10. Diasio RB, Beavers TL, Carpenter JT. Familial deficiency of dihydropyrimidine dehydrogenase (Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity). J Clin Invest. 1988;81(1):47–51
  11. Tuchman M, Stoeckeler JS, Kiang DT, et al. Familial pyrimidinemia and pyrimidinuria associated with severe fluorouracil toxicity. N Engl J Med. 1985;313(4):245–249
  12. Van Kuilenburg AB, Meinsma R, Zoetekouw L, et al. High prevalence of the IVS14 + 1G>A mutation in the dihydropyrimidine dehydrogenase gene of patients with severe 5-fluorouracil-associated toxicity. Pharmacogenetics. 2002;12(7):555–558
  13. Wei X, McLeod HL, McMurrough J, et al. Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. J Clin Invest. 1996;98(3):610–615
  14. Milano G, Etienne MC. Potential importance of dihydropyrimidine dehydrogenase (DPD) in cancer chemotherapy. Pharmacogenetics. 1994;4(6):301–306
  15. Yen JL, McLeod HL. Should DPD analysis be required prior to prescribing fluoropyrimidines?. Eur J Cancer. 2007;43(6):1011–1016
  16. Van Kuilenburg AB, Meinsma R, Zoetekouw L, et al. Increased risk of grade IV neutropenia after administration of 5-fluorouracil due to a dihydropyrimidine dehydrogenase deficiency: high prevalence of the IVS14+1g>a mutation. Int J Cancer. 2002;101(3):253–258
  17. Ezzeldin HH, Lee AM, Mattison LK, et al. Methylation of the DPYD promoter: an alternative mechanism for dihydropyrimidine dehydrogenase deficiency in cancer patients. Clin Cancer Res. 2005;11(24 Pt. 1):8699–8705
  18. Magne N, Etienne-Grimaldi MC, Cals L, et al. Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity. Br J Clin Pharmacol. 2007;64(2):237–240
  19. Gutheil J, Finucane D. Antimetabolites. In:  Perry M editors. The Chemotherapy Source Book. ed 3. Philadelphia, PA: Lippincott Williams & Wilkins; 2001;p. 208–227
  20. Leichman CG, Lenz HJ, Leichman L, et al. Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluorouracil and weekly leucovorin. J Clin Oncol. 1997;15(10):3223–3229
  21. Lenz HJ, Leichman CG, Danenberg KD, et al. Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival. J Clin Oncol. 1996;14(1):176–182
  22. Johnston PG, Lenz HJ, Leichman CG, et al. Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. Cancer Res. 1995;55(7):1407–1412
  23. Kawakami K, Omura K, Kanehira E, et al. Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers. Anticancer Res. 1999;19(4B):3249–3252
  24. Pullarkat ST, Stoehlmacher J, Ghaderi V, et al. Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogen J. 2001;1(1):65–70
  25. Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004;22(1):23–30
  26. Saltz LB, Niedzwiecki D, Hollis D, et al. Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. J Clin Oncol. 2007;25(23):3456–3461
  27. Rothenberg ML, Meropol NJ, Poplin EA, et al. Mortality associated with irinotecan plus bolus fluorouracil/leucovorin: summary findings of an independent panel. J Clin Oncol. 2001;19(18):3801–3807
  28. Iyer L, Das S, Janisch L, et al. UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity. Pharmacogen J. 2002;2(1):43–47
  29. Innocenti F, Undevia SD, Iyer L, et al. Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol. 2004;22(8):1382–1388
  30. Marcuello E, Altes A, Menoyo A, et al. UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer. Br J Cancer. 2004;91(4):678–682
  31. Rouits E, Boisdron-Celle M, Dumont A, et al. Relevance of different UGT1A1 polymorphisms in irinotecan-induced toxicity: a molecular and clinical study of 75 patients. Clin Cancer Res. 2004;10(15):5151–5159
  32. Ando Y, Saka H, Ando M, et al. Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. Cancer Res. 2000;60(24):6921–6926
  33. Hoskins JM, Goldberg RM, Qu P, et al. UGT1A1*28 genotype and irinotecan-induced neutropenia: dose matters. J Natl Cancer Inst. 2007;99(17):1290–1295

PII: S1043-1489(08)00057-2

doi: 10.1053/j.scrs.2008.09.007

Seminars in Colon & Rectal Surgery
Volume 19, Issue 4 , Pages 226-230 , December 2008

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