Display options
Share it on

Biologics. 2007 Jun;1(2):77-91.

Cetuximab in the management of colorectal cancer.

Biologics : targets & therapy

Heinz-Josef Lenz

Affiliations

  1. Division of Medical Oncology, University of Southern California/ Norris, Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA.

PMID: 19707318 PMCID: PMC2721306

Abstract

Cetuximab, a chimeric IgG1 monoclonal antibody that targets the ligand-binding domain of the epidermal growth factor receptor (EGFR), is active in metastatic colorectal cancer (mCRC). As an IgG1 antibody, cetuximab may exert its antitumor efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. Clinical trials established the role of cetuximab, particularly with irinotecan, in irinotecan-refractory/heavily pretreated patients. More recent studies show promising activity in second-line treatment after oxaliplatin-based therapy failure, and with first-line chemotherapy, where increased response rates seen with adding cetuximab to first-line therapy for mCRC may increase chances for curative surgery in a population for whom the therapy goal would otherwise be palliative. Cetuximab is generally well tolerated; common toxicities are acne-form rash and hypomagnesemia. Rash intensity is associated with clinical efficacy, and in the future, may be used as a marker for optimal drug exposure. Cetuximab activity in mCRC is not correlated with EGFR expression, and consequently other markers will be needed to identify the most likely responders. Cetuximab has clinically emerged as a core agent, along with 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab, for overall mCRC management to optimize survival. Ongoing studies are exploring best combinations of cetuximab with these other agents to maximize patient outcome.

Keywords: cetuximab; colorectal cancer; epidermal growth factor receptor

References

  1. J Clin Oncol. 2000 Aug;18(16):2938-47 - PubMed
  2. Eur J Cancer. 2001 Sep;37 Suppl 4:S9-15 - PubMed
  3. Lancet. 1998 Oct 31;352(9138):1413-8 - PubMed
  4. J Am Acad Dermatol. 2007 Feb;56(2):317-26 - PubMed
  5. Lancet. 1998 Oct 31;352(9138):1407-12 - PubMed
  6. Tissue Antigens. 2003 Mar;61(3):189-202 - PubMed
  7. Oncology. 2002;63(1):92-8 - PubMed
  8. Cancer Metastasis Rev. 2005 Dec;24(4):487-99 - PubMed
  9. N Engl J Med. 2004 Jul 22;351(4):337-45 - PubMed
  10. J Clin Oncol. 2006 Jul 20;24(21):3354-60 - PubMed
  11. N Engl J Med. 2006 Feb 9;354(6):567-78 - PubMed
  12. Ann Pharmacother. 1994 Feb;28(2):220-6 - PubMed
  13. J Clin Oncol. 2007 Aug 20;25(24):3712-8 - PubMed
  14. Cancer Res. 1999 Apr 15;59(8):1935-40 - PubMed
  15. Clin Colorectal Cancer. 2006 Jul;6(2):152-6 - PubMed
  16. Int J Cancer. 2007 Feb 15;120(4):781-7 - PubMed
  17. Ann Oncol. 2007 Feb;18(2):305-10 - PubMed
  18. Lancet. 2000 Mar 25;355(9209):1041-7 - PubMed
  19. N Engl J Med. 2004 Jun 3;350(23):2335-42 - PubMed
  20. J Clin Oncol. 2004 Apr 1;22(7):1209-14 - PubMed
  21. J Clin Oncol. 2007 Apr 20;25(12):1539-44 - PubMed
  22. J Clin Oncol. 2004 Apr 1;22(7):1201-8 - PubMed
  23. Int J Radiat Oncol Biol Phys. 2006 Dec 1;66(5):1384-90 - PubMed
  24. Clin Cancer Res. 2002 May;8(5):994-1003 - PubMed
  25. Ann Oncol. 2005 Jan;16(1):102-8 - PubMed
  26. J Clin Oncol. 2003 Nov 1;21(21):3940-7 - PubMed
  27. Ann Oncol. 2006 Mar;17(3):450-6 - PubMed
  28. Nat Rev Mol Cell Biol. 2001 Feb;2(2):127-37 - PubMed
  29. J Clin Oncol. 2005 Dec 20;23(36):9441-2 - PubMed
  30. Cancer. 2000 Jul 1;89(1):74-82 - PubMed
  31. J Clin Oncol. 2004 Jan 15;22(2):229-37 - PubMed
  32. Clin Cancer Res. 2007 Mar 1;13(5):1552-61 - PubMed
  33. J Natl Compr Canc Netw. 2010 Jan;8(1):106-20 - PubMed
  34. Drugs Today (Barc). 2005 Feb;41(2):107-27 - PubMed
  35. Ann Oncol. 2007 Apr;18(4):738-44 - PubMed
  36. Blood. 2004 Nov 1;104(9):2635-42 - PubMed
  37. Cancer Res. 2006 Apr 15;66(8):3992-5 - PubMed
  38. Panminerva Med. 2001 Sep;43(3):177-209 - PubMed
  39. J Clin Oncol. 2006 Oct 20;24(30):4914-21 - PubMed
  40. Expert Opin Biol Ther. 2006 Nov;6(11):1229-35 - PubMed
  41. J Clin Oncol. 2005 May 20;23(15):3536-44 - PubMed
  42. J Clin Oncol. 2007 Aug 1;25(22):3230-7 - PubMed
  43. Br J Cancer. 2007 Apr 23;96(8):1166-9 - PubMed
  44. J Clin Oncol. 2005 Aug 1;23(22):5235-46 - PubMed
  45. Clin Colorectal Cancer. 2005 Apr;5 Suppl 1:S19-27 - PubMed
  46. J Biol Chem. 2005 Sep 2;280(35):31182-9 - PubMed
  47. Clin Cancer Res. 1999 Apr;5(4):909-16 - PubMed
  48. N Engl J Med. 2000 Sep 28;343(13):905-14 - PubMed
  49. J Clin Oncol. 2005 Mar 20;23(9):1803-10 - PubMed
  50. J Natl Cancer Inst. 2005 Aug 17;97(16):1221-4 - PubMed
  51. Oncology (Williston Park). 2006 Apr;20(5 Suppl 2):5-13 - PubMed
  52. Int J Biochem Cell Biol. 1999 Jun;31(6):637-43 - PubMed

Publication Types