Korean J Gastroenterol.  2013 Mar;61(3):128-135. 10.4166/kjg.2013.61.3.128.

A Perspective: Role of Targeted Therapy in Colon Cancer

Affiliations
  • 1Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea. JBI@MED.YU.AC.KR

Abstract

Colorectal cancer is the third most common malignant disease in incidence according to a report in 2009 from Korea. The 5-fluorouracil (5-FU) remains to be a major chemotherapeutic agents. But, over the last 10-15 years, the treatment pattern for metastatic colorectal cancer changed significantly. Irinotecan and oxaliplatin are cytotoxic drugs, or bevacizumab and cetuximab are monoclonal antibodies against molecular targets. The introduction of novel agents targeting specific molecular features of cancer cells promises more options and marked improvements in efficacy for the treatment of metastatic colon cancer. Bevacizumab has been shown to extend survival in colorectal cancer when used in combination with irinotecan and 5-FU-based chemotherapy, and the addition of cetuximab to irinotecan and 5-FU-based chemotherapy eliminates irinotecan resistance. Better understanding of the tumor biology and the molecular pathway and mechanisms of tumorigenesis has led to the discovery of novel agents with improved outcomes.

Keyword

Colorectal neoplasms; Targeted molecular therapy

MeSH Terms

Antibodies, Monoclonal/therapeutic use
Antibodies, Monoclonal, Humanized/therapeutic use
Antineoplastic Agents/*therapeutic use
Colonic Neoplasms/*drug therapy/metabolism/pathology
Humans
Molecular Targeted Therapy
Receptor, Epidermal Growth Factor/antagonists & inhibitors/metabolism
Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Agents
Vascular Endothelial Growth Factor A
Receptor, Epidermal Growth Factor

Reference

References

1. Korea Central Cancer Resistry. Annual report of the Korea Central Cancer Registry 2009. Goyang: National Cancer Center;2011.
2. Kim KJ, Li B, Houck K, Winer J, Ferrara N. The vascular endothelial growth factor proteins: identification of biologically relevant regions by neutralizing monoclonal antibodies. Growth Factors. 1992; 7:53–64.
Article
3. Gordon MS, Margolin K, Talpaz M, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol. 2001; 19:843–850.
Article
4. Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol. 2003; 21:60–65.
Article
5. Kabbinavar FF, Schulz J, McCleod M, et al. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol. 2005; 23:3697–3705.
Article
6. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350:2335–2342.
Article
7. Fuchs C, Marshall J, Mitchell E, et al. Updated results of BICC-C study comparing first-line irinotecan/fluoropymidine combinations with or without celecoxib in mCRC: update defficacy data. J Clin Oncol. 2007; 25(Suppl):4027.
8. Hochster HS, Hart LL, Ramanathan RK, Hainsworth JD, Hedrick EE, Childs BH. Safety and efficacy of oxaliplatin/fluoropyrimidine regimens with bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC): final analysis of the TREE Study. J Clin Oncol. 2006; 24(18 Suppl):148s. (abstr 3510).
9. Tyagi P, Grothey A. Commentary on a phase III trial of bevacizumab plus XELOX or FOLFOX4 for first-line treatment of metastatic colorectal cancer: the NO16966 trial. Clin Colorectal Cancer. 2006; 6:261–264.
Article
10. Giantonio BJ, Catalano PJ, Meropol NJ, et al. High-dose bevacizumab improves survival when combined with FOLFOX4 in previously treated advanced colorectal cancer: results from the Eastern Cooperative Oncology Group (ECOG) study E3200. J Clin Oncol. 2005; 23(16 Suppl):1s. (abstr 2).
Article
11. Saltz LB, Clarke S, Díaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008; 26:2013–2019.
Article
12. Giantonio BJ, Catalano PJ, Meropol NJ, et al. Eastern Cooperative Oncology Group Study E3200. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007; 25:1539–1544.
Article
13. Ziras N, Polyzos A, Kakolyris S, et al. CAPIRI (capecitabine, irinotecan)+ bevacizumab vs FOLFIRI (folinic acid, 5 fluorouracil, irinotecan)+ bevacizumab for the treatment of patients with metastatic colorectal cancer (mCRC): Interim analysis for safety of a randomizedphase III trial. J Clin Oncol. 2008; 26(Suppl):abstr 15008.
14. Avastin product information [Internet]. South San Francisco (CA): Genentech Inc.;2013. [cited 2013 Mar 7]. Available from:. www.gene.com/gene/products/information/pdf/avastinprescribing.pdf.
15. Folprecht G, Lutz MP, Schöffski P, et al. Cetuximab and irinotecan/5-fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma. Ann Oncol. 2006; 17:450–456.
Article
16. Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol. 2004; 22:1201–1208.
Article
17. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004; 351:337–345.
Article
18. Saltz LB, Lenz H, Hochster H, et al. Randomized phase II trial of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer. J Clin Oncol. 2005; 23(Suppl):248s.
Article
19. Van Cutsem E, Lang I, Folprecht G, et al. Cetuximab plus FOLFIRI in the treatment of metastatic colorectal cancer (mCRC): the influence of KRAS and BRAF biomarkers on outcome: updated data from the CRYSTAL trial. Abstract 281. American Society of Clinical Oncology. 2010 Gastrointestinal Cancers Symposium. Alexandria (VA): American Society of Clinical Oncology;2010.
20. Loupakis F, Pollina L, Stasi I, et al. PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. J Clin Oncol. 2009; 27:2622–2629.
Article
21. Lièvre A, Bachet JB, Boige V, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008; 26:374–379.
22. Laurent-Puig P, Cayre A, Manceau G, et al. Analysis of PTEN, BRAF, and EGFR status in determining benefit from cetuximab therapy in wild-type KRAS metastatic colon cancer. J Clin Oncol. 2009; 27:5924–5930.
Article
23. Tabernero J, Van Cutsem E, Díaz-Rubio E, et al. Phase II trial of cetuximab in combination with fluorouracil, leucovorin, and oxaliplatin in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2007; 25:5225–5232.
Article
24. Venook A, Niedzwiecki D, Hollis D, et al. Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV(FOLFOX) ±cetuximab for patients (pts) with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results. J Clin Oncol. 2006; 24(18 Suppl):148s. (abstr 3509).
25. Van Cutsem E, Nowacki M, Lang I, et al. Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial. J Clin Oncol. 2007; 25(18 Suppl):abstr 4000.
Article
26. Sobrero AF, Maurel J, Fehrenbacher L, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol. 2008; 26:2311–2319.
Article
27. Chung KY, Shia J, Kemeny NE, et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol. 2005; 23:1803–1810.
Article
28. Agero AL, Dusza SW, Benvenuto-Andrade C, Busam KJ, Myskowski P, Halpern AC. Dermatologic side effects associated with the epidermal growth factor receptor inhibitors. J Am Acad Dermatol. 2006; 55:657–670.
Article
29. Fakih MG, Wilding G, Lombardo J. Cetuximab-induced hypomagnesemia in patients with colorectal cancer. Clin Colorectal Cancer. 2006; 6:152–156.
Article
30. Gravalos C, Cassinello J, García-Alfonso P, Jimeno A. Integration of panitumumab into the treatment of colorectal cancer. Crit Rev Oncol Hematol. 2010; 74:16–26.
Article
31. Van Cutsem E, Peeters M, Siena S, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007; 25:1658–1664.
Article
32. Douillard JY, Siena S, Cassidy J, et al. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010; 28:4697–4705.
Article
33. Peeters M, Price TJ, Cervantes A, et al. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010; 28:4706–4713.
34. Tabernero J, Rojo F, Jimenez E, et al. A phase I PK and serial tumor and skin pharmacodynamic (PD) study of weekly (q1w), every 2-week (q2w) or every 3-week (q3w) 1-hour (h) infusion EMD72000, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients (pt) with advanced tumors. Proc Am Soc Clin Oncol. 2003; 22:192. (A192):
35. A study to assess the efficacy and safety of lenalidomide in combination with cetuximab in pre-treated patients with KRAS mutant colorectal cancer [Internet]. National Institutes of Health;2010 Aug 10. [cited 2010 Oct 15]. Available from:. www.clinicaltrials.gov/ct2/show/NCT01032291?term=colon+Kras+mutant&rank=3.
36. Efficacy and safety study of imprime PGG with cetuximab in subjects with stage IV KRAS-mutated colorectal cancer [Internet]. National Institutes of Health;2010 March 30. [cited 2010 Oct 15]. Available from:. www.clinicaltrials.gov/ct2/show/NCT00912327?term=colon+Kras+mutant&rank=9.
37. Gollamudi R, Ghalib MH, Desai KK, et al. Intravenous administration of Reolysin, a live replication competent RNA virus is safe in patients with advanced solid tumors. Invest New Drugs. 2010; 28:641–649.
Article
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