This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Venook, A. Search for Related Content PubMed PubMed Citation Articles by Venook, A.

Critical Evaluation of Current Treatments in Metastatic Colorectal Cancer

Division of Medical Oncology, Clinical Research Office, University of California Cancer Center, San Francisco, California, USA

Correspondence: Alan Venook, M.D., Division of Medical Oncology, Clinical Research Office, University of California Cancer Center, Box 1705, 1600 Divisadero, San Francisco, California 94115-1705, USA. Telephone: 415-353-9888; Fax: 415-353-9959; e-mail: venook{at}cc.ucsf.edu

Fluorouracil (FU) has been the mainstay of treatment for metastatic colorectal cancer (mCRC) for many years. However, in recent years, newer chemotherapeutic agents, particularly irinotecan (Campostar^®; Pfizer Pharmaceuticals, New York, NY, http://www.pfizer.com) and more recently oxaliplatin (Eloxatin^®; Sanofi-Aventis Inc., New York, NY, http://www.sanofi-aventis.com), have been shown to improve survival in combination with FU-based therapies. These agents were therefore incorporated into first- and second-line treatment strategies. The development of targeted agents that are tumor specific with better toxicity profiles than chemotherapeutic agents has widened the spectrum of therapies for this disease. The U.S. Food and Drug Administration (FDA) recently approved two targeted agents for treating mCRC: an antivascular endothelial growth factor monoclonal antibody (mAb), bevacizumab (Avastin^®; Genentech, Inc., South San Francisco, CA, http://www.gene.com), in combination with first-line 5-FU-based chemotherapy regimens and the human epidermal growth factor receptor (HER-1/EGFR)-targeted mAb cetuximab (Erbitux^®; ImClone Systems, Inc., New York, NY, http://www.imclone.com) as monotherapy or in combination with irinotecan as second-line therapy in refractory cancer. These newer, more effective agents are improving clinical outcome for patients with mCRC. However, as the number of agents has increased, choosing the most effective treatment strategy has become increasingly complex. This review discusses the role of the individual agents in the treatment of mCRC and identifies the most effective regimens.

Key Words. Fluorouracil • Irinotecan • Oxaliplatin • Bevacizumab • Cetuximab • Vascular endothelial growth factor • VEGF

This article has been cited by other articles:

				K.-L. G. Spindler, R. F. Andersen, L. H. Jensen, J. Ploen, and A. Jakobsen EGF61A>G polymorphism as predictive marker of clinical outcome to first-line capecitabine and oxaliplatin in metastatic colorectal cancer Ann. Onc., October 22, 2009; (2009) mdp336v1. [Abstract] [Full Text] [PDF]

				I. Lansdorp-Vogelaar, M. van Ballegooijen, A. G. Zauber, J. D. F. Habbema, and E. J. Kuipers Effect of Rising Chemotherapy Costs on the Cost Savings of Colorectal Cancer Screening J Natl Cancer Inst, October 21, 2009; 101(20): 1412 - 1422. [Abstract] [Full Text] [PDF]

				E. Aranda, M. Valladares, M. Martinez-Villacampa, M. Benavides, A. Gomez, B. Massutti, E. Marcuello, M. Constenla, J. C. Camara, A. Carrato, et al. Randomized study of weekly irinotecan plus high-dose 5-fluorouracil (FUIRI) versus biweekly irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI) as first-line chemotherapy for patients with metastatic colorectal cancer: a Spanish Cooperative Group for the Treatment of Digestive Tumors Study Ann. Onc., February 1, 2009; 20(2): 251 - 257. [Abstract] [Full Text] [PDF]

				R. I. Sharma and T. A.D. Smith Colorectal Tumor Cells Treated with 5-FU, Oxaliplatin, Irinotecan, and Cetuximab Exhibit Changes in 18F-FDG Incorporation Corresponding to Hexokinase Activity and Glucose Transport J. Nucl. Med., August 1, 2008; 49(8): 1386 - 1394. [Abstract] [Full Text] [PDF]

				M. Jhawer, S. Goel, A. J. Wilson, C. Montagna, Y.-H. Ling, D.-S. Byun, S. Nasser, D. Arango, J. Shin, L. Klampfer, et al. PIK3CA Mutation/PTEN Expression Status Predicts Response of Colon Cancer Cells to the Epidermal Growth Factor Receptor Inhibitor Cetuximab Cancer Res., March 15, 2008; 68(6): 1953 - 1961. [Abstract] [Full Text] [PDF]

				M. Emaduddin, D. C. Bicknell, W. F. Bodmer, and S. M. Feller Cell growth, global phosphotyrosine elevation, and c-Met phosphorylation through Src family kinases in colorectal cancer cells PNAS, February 19, 2008; 105(7): 2358 - 2362. [Abstract] [Full Text] [PDF]

				R. L. Mahtani and J. S. Macdonald Synergy Between Cetuximab and Chemotherapy in Tumors of the Gastrointestinal Tract Oncologist, January 1, 2008; 13(1): 39 - 50. [Abstract] [Full Text] [PDF]

				R. M. Goldberg, M. L. Rothenberg, E. Van Cutsem, A. B. Benson III, C. D. Blanke, R. B. Diasio, A. Grothey, H.-J. Lenz, N. J. Meropol, R. K. Ramanathan, et al. The Continuum of Care: A Paradigm for the Management of Metastatic Colorectal Cancer Oncologist, January 1, 2007; 12(1): 38 - 50. [Abstract] [Full Text] [PDF]

				R. H. Wilson Novel Therapeutic Developments Other Than EGFR and VEGF Inhibition in Colorectal Cancer Oncologist, October 1, 2006; 11(9): 1018 - 1024. [Abstract] [Full Text] [PDF]

				M. P. Cunningham, H. Thomas, Z. Fan, and H. Modjtahedi Responses of Human Colorectal Tumor Cells to Treatment with the Anti-Epidermal Growth Factor Receptor Monoclonal Antibody ICR62 Used Alone and in Combination with the EGFR Tyrosine Kinase Inhibitor Gefitinib. Cancer Res., August 1, 2006; 66(15): 7708 - 7715. [Abstract] [Full Text] [PDF]

				B. Vincenzi, D. Santini, A. Russo, M. Silletta, M. Gavasci, F. Battistoni, G. Di Cuonzo, L. Rocci, N. Gebbia, and G. Tonini Angiogenesis modifications related with cetuximab plus irinotecan as anticancer treatment in advanced colorectal cancer patients Ann. Onc., May 1, 2006; 17(5): 835 - 841. [Abstract] [Full Text] [PDF]

				G. Wu, R. F. Barth, W. Yang, S. Kawabata, L. Zhang, and K. Green-Church Targeted delivery of methotrexate to epidermal growth factor receptor-positive brain tumors by means of cetuximab (IMC-C225) dendrimer bioconjugates Mol. Cancer Ther., January 1, 2006; 5(1): 52 - 59. [Abstract] [Full Text] [PDF]