The management of colorectal cancer relies heavily on the combination of the pyrimidine analog antimetabolite 5-fluorouracil with the platinum-based drug oxaliplatin or the topoisomerase inhibitor irinotecan. Optimization of dosing and scheduling of these agents to improve response and survival continues to evolve. Meanwhile, the rational targeting of molecular signaling pathways that are involved in the etiology of malignancies is currently one of the most promising strategies in novel anticancer drug development. New classes of drugs that target the epidermal growth factor receptor are among the most clinically advanced molecular-targeted therapies and have shown efficacy in colorectal cancer. The current status of epidermal growth factor receptor-targeted therapeutic agents is reviewed, with emphasis on their role in the management of colorectal cancer.
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References
RJ Rutman A Cantarow KE Paschkis (1954) ArticleTitleStudies in 2-acetylaminofluorene carcinogenesis. II. The in vitro uptake of alanine-1-C14 by preneoplastic liver and hepatoma mitochondrial protein Cancer Res 14 115–118 Occurrence Handle13126945 Occurrence Handle1:CAS:528:DyaG2cXmvV2gtA%3D%3D
B Vogelstein KW Kinzler (2004) ArticleTitleCancer genes and the pathways they control Nat Med 10 789–799 Occurrence Handle15286780 Occurrence Handle10.1038/nm1087 Occurrence Handle1:CAS:528:DC%2BD2cXmtFWrt7o%3D
S Yano K Kondo M Yamaguchi et al. (2003) ArticleTitleDistribution and function of EGFR in human tissue and the effect of EGFR tyrosine kinase inhibition Anticancer Res 23 3639–3650 Occurrence Handle14666659 Occurrence Handle1:CAS:528:DC%2BD2cXkvFWn
AP Venook (2005) ArticleTitleEpidermal growth factor receptor-targeted treatment for advanced colorectal carcinoma Cancer 103 2435–2446 Occurrence Handle15880563 Occurrence Handle10.1002/cncr.21123 Occurrence Handle1:CAS:528:DC%2BD2MXlvVCktL4%3D
Y Yarden MX Sliwkowski (2001) ArticleTitleUntangling the ErbB signalling network Nat Rev Mol Cell Biol 2 127–137 Occurrence Handle11252954 Occurrence Handle10.1038/35052073 Occurrence Handle1:CAS:528:DC%2BD3MXivVWnt7k%3D
J Mendelsohn J Baselga (2003) ArticleTitleStatus of epidermal growth factor receptor antagonists in the biology and treatment of cancer J Clin Oncol 21 2787–2799 Occurrence Handle12860957 Occurrence Handle10.1200/JCO.2003.01.504 Occurrence Handle1:CAS:528:DC%2BD2cXptlCktbo%3D
JA McKay LJ Murray S Curran et al. (2002) ArticleTitleEvaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases Eur J Cancer 38 2258–2264 Occurrence Handle12441262 Occurrence Handle10.1016/S0959-8049(02)00234-4 Occurrence Handle1:STN:280:DC%2BD38notVyquw%3D%3D
D Cunningham Y Humblet S Siena et al. (2004) ArticleTitleCetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer N Engl J Med 351 337–345 Occurrence Handle15269313 Occurrence Handle10.1056/NEJMoa033025 Occurrence Handle1:CAS:528:DC%2BD2cXlvFGitbk%3D
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: colorectal cancer. Version 2. 2006. 11–15–2005
M Moroni S Veronese S Benvenuti et al. (2005) ArticleTitleGene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study Lancet Oncol 6 279–286 Occurrence Handle15863375 Occurrence Handle10.1016/S1470-2045(05)70102-9 Occurrence Handle1:CAS:528:DC%2BD2MXjs1Krsb8%3D
Lenz H-J, Mayer RJ, Mirtsching B, et al. Consistent response to treatment with cetuximab monotherapy in patients with metastatic colorectal cancer. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings, 2005;23:255s:3536a
Saltz LB, Lenz H, Kindler H, et al. Interim report of randomized phase II trial of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings, 2005;23:248s:3508a
Grothe W, Arnold D, Peinert S, et al. Cetuximab with oxaliplatin and capecitabine (CAPOX) in patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapy. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings, 2005;23:288s:3669a
Rougier P, Raoul JL, Van Laethem JL, et al. Cetuximab+FOLFIRI as first-line treatment for metastatic colorectal CA. J Clin Oncol, 2004 ASCO Annual Meeting Proceedings, 2005;22:249s:3513a
Diaz-Rubio E, Tabernero J, Van Cutsem E, et al. Cetuximab in combination with oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with epidermal growth factor receptor (EGFR)—expressing metastatic colorectal cancer: An international phase II study. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings, 2005;23:254s:3535a
Jennis A, Polikoff J, Mitchell E, et al. Erbitux (cetuximab) plus FOLFOX for colorectal cancer (EXPLORE): preliminary efficacy analysis of a randomized phase III trial. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings, 2005;23:265s:3574a
Malik I, Hecht JR, Patnaik A, et al. Safety and efficacy of panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC). J Clin Oncol, 2005 ASCO Annual Meeting Proceedings, 2005;23:251s:3520a
Benson A. Panitumumab, a fully-human IgG2 antibody treatment for colorectal cancer. Paper presented at: The 23rd annual Chemotherapy Foundation Symposium November 2--5, 2005, New York, New York [Abstract 4]
Peeters M, Van Cutsem E, Siena S, et al. A phase 3, multicenter, randomized controlled trial of panitumumab plus best supportive care (BSC) vs BSC alone in patients with metastatic colorectal cancer. Paper presented at: American Association of Cancer Research Annual Meeting; April 1, 2006; Washington, DC [Abstract CP-1]
U Vanhoefer M Tewes F Rojo et al. (2004) ArticleTitlePhase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor J Clin Oncol 22 175–184 Occurrence Handle14701780 Occurrence Handle10.1200/JCO.2004.05.114 Occurrence Handle1:CAS:528:DC%2BD2cXpsVKhsrk%3D
Trarbach T, Beyer T, Schleucher N, et al. A randomized phase I study of the humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody EMD 72000 in subjects with advanced gastrointestinal cancers. J Clin Oncol, 2004 ASCO Annual Meeting Proceedings, 2004;22:199s:3018a
ML Rothenberg B LaFleur DE Levy et al. (2005) ArticleTitleRandomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma J Clin Oncol 23 9265–9274 Occurrence Handle16361624 Occurrence Handle10.1200/JCO.2005.03.0536 Occurrence Handle1:CAS:528:DC%2BD28Xnt1yntQ%3D%3D
HL Kindler G Friberg L Skoog K Wade-Oliver EE Vokes (2005) ArticleTitlePhase I/II trial of gefitinib and oxaliplatin in patients with advanced colorectal cancer Am J Clin Oncol 28 340–344 Occurrence Handle16062074 Occurrence Handle10.1097/01.coc.0000159558.19631.d5 Occurrence Handle1:CAS:528:DC%2BD2MXpvVWjtb0%3D
ML Veronese W Sun B Giantonio et al. (2005) ArticleTitleA phase II trial of gefitinib with 5-fluorouracil, leucovorin, and irinotecan in patients with colorectal cancer Br J Cancer 92 1846–1849 Occurrence Handle15870719 Occurrence Handle10.1038/sj.bjc.6602569 Occurrence Handle1:CAS:528:DC%2BD2MXkt1Sgsr4%3D
T Kuo CD Cho J Halsey et al. (2005) ArticleTitlePhase II study of gefitinib, fluorouracil, leucovorin, and oxaliplatin therapy in previously treated patients with metastatic colorectal cancer J Clin Oncol 23 5613–5619 Occurrence Handle16110021 Occurrence Handle10.1200/JCO.2005.08.359 Occurrence Handle1:CAS:528:DC%2BD2MXhtVersr%2FE
Fisher GA, Kuo T, Cho CD, et al. A phase II study of gefitinib in combination with FOLFOX-4 (IFOX) in patients with metastatic colorectal cancer. J Clin Oncol, 2004 ASCO Annual Meeting Proceedings, 2004;22:248s:3514
Zampino MG, Lorizzo K, Massacesi C, et al. First-line gefitinib combined with simplified FOLFOX-6 in patients with epidermal growth factor receptor-positive advanced colorectal cancer. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings, 2005;23:285s:3659a
Jimeno A, Sevilla I, Gravalos C, et al. Phase I/II trial of capecitabine and gefitinib in patients with advanced colorectal cancer after failure of first-line therapy. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings, 2005;23:235s:3176a
Oza AM, Townsley CA, Siu LL, et al. Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal cancer. Paper presented at: American Society of Clinical Oncology Annual Meeting; May 31, 2003; Chicago, Illinois [Abstract 785]
Keilholz U, Arnold D, Niederle N, et al. Erlotinib as 2nd and 3rd line monotherapy in patients with metastatic colorectal cancer: results of a multicenter two-cohort phase II trial. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings, 2005;23:264s:3575a
Meyerhardt JA, Xhu A, Enzinger PC, et al. Phase II study of capecitabine, oxaliplatin and erlotinib in previously treated patients with metastatic colorectal cancer (MCRC). J Clin Oncol, 2004 ASCO Annual Meeting Proceedings, 2005;22:265s:3580a
Fields AL, Rinaldi DA, Henderson CA, et al. An open-label multicenter phase II study of oral lapatinib (GW572016) as single agent, second-line therapy in patients with metastatic colorectal cancer. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings, 2005;23:266s:3583a
J Mendelsohn J Baselga (2000) ArticleTitleThe EGF receptor family as targets for cancer therapy Oncogene 19 6550–6565 Occurrence Handle11426640 Occurrence Handle10.1038/sj.onc.1204082 Occurrence Handle1:CAS:528:DC%2BD3MXhsF2ku7k%3D
AM Petit J Rak MC Hung et al. (1997) ArticleTitleNeutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors Am J Pathol 151 1523–1530 Occurrence Handle9403702 Occurrence Handle1:CAS:528:DyaK1cXpt1Gn
H Mellstedt (2003) ArticleTitleMonoclonal antibodies in human cancer Drugs of Today 39 IssueIDSuppl C 1–16 Occurrence Handle14988743 Occurrence Handle1:CAS:528:DC%2BD2cXis1Cltg%3D%3D
Khazaeli MB, LoBuglio AF, Falcey JW, Paulter VJ, Fetzer KM, Waksal HW. Low immunogenicity of a chimeric monoclonal antibody (MoAb), IMC-C225, used to treat epidermal growth factor recepto-positive tumors. Paper presented at: American Society of Clinical Oncology Annual Meeting; May 20, 2000; New Orleans, Louisiana [Abstract 808]
D Schrag KY Chung C Flombaum L Saltz (2005) ArticleTitleCetuximab therapy and symptomatic hypomagnesemia J Natl Cancer Inst 97 1221–1224 Occurrence Handle16106027 Occurrence Handle1:CAS:528:DC%2BD2MXpsVaksL8%3D Occurrence Handle10.1093/jnci/dji242
Saltz L, Rubin M, Hochster H, et al. Cetuximab (IMC-C225) plus Irinotecan (CPT-11) is active in CPT-11 refractory colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR). Paper presented at: American Society of Clinical Oncology Annual Meeting; May 12, 2001; San Francisco, California [Abstract 7]
Rosenberg AH, Loehrer P, Needle MN, et al. Erbitux (IMC-C255) plus weekly irinotecan (CPT-11), fluorouracil (5FU) and leucovorin (LV) in colorectal cancer (CRC) that expresses the epidermal growth factor receptor (EFGr). Paper presented at: American Society of Clinical Oncology Annual Meeting; May 18, 2002; Orlando, Florida [Abstract 536].
Spitzer G, Zackon I, Stella P, Zehngebot L, Henderson C. Anti-epidermal growth factor (EGFR) antibody, cetuximab, in patients with stage IV colorectal carcinoma who failed all standard therapy: Final report of an access protocol. J Clin Oncol, 2005 ASCO Annual Meeting Proceedings, 2005;23:282s:3646a
KA Foon XD Yang LM Weiner et al. (2004) ArticleTitlePreclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody Int J Radiat Oncol Biol Phys 58 984–990 Occurrence Handle14967460 Occurrence Handle10.1016/j.ijrobp.2003.09.098 Occurrence Handle1:CAS:528:DC%2BD2cXhtVygsr4%3D
Berlin J, Malik I, Picus J, et al. Panitumumab therapy with irinotecan, 5-fluorouracil, and leucovorin (IFL) in patients (pts) with metastatic colorectal cancer (mCRC). Ann Oncol 2004;15(Suppl 3):70
T Crombet M Osorio T Cruz et al. (2004) ArticleTitleUse of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients J Clin Oncol 22 1646–1654 Occurrence Handle15117987 Occurrence Handle10.1200/JCO.2004.03.089 Occurrence Handle1:CAS:528:DC%2BD2cXpsVWlsr8%3D
Pfister D, Lipton A, Belt R, et al. A phase I trial of the epidermal growth factor receptor (EGFR)-directed bispecific antibody (BsAB) MDX-447 in patients with solid tumors. Paper presented at: American Society of Clinical Oncology Annual Meeting; May 15, 1999; Atlanta, Georgia [Abstract 1667]
N Thatcher A Chang P Parikh et al. (2005) ArticleTitleGefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer) Lancet 366 1527–1537 Occurrence Handle16257339 Occurrence Handle10.1016/S0140-6736(05)67625-8 Occurrence Handle1:CAS:528:DC%2BD2MXhtFKhsbfP
CL Arteaga (2003) ArticleTitleErbB-targeted therapeutic approaches in human cancer Exp Cell Res 284 122–130 Occurrence Handle12648471 Occurrence Handle10.1016/S0014-4827(02)00104-0 Occurrence Handle1:CAS:528:DC%2BD3sXitVylt7c%3D
Bridgewater JA, Harrison M, Broby S, Currie C, Propper D. Phase I clinical trial of Gefitinib and 5FU in patients with 5FU-refractory colorectal cancer. Paper presented at: American Society of Clinical Oncology Annual Meeting Gastrointestinal Cancers Symposium; January 27, 2005; Miami, Florida [Abstract 292]
TD Barber B Vogelstein KW Kinzler VE Velculescu (2004) ArticleTitleSomatic mutations of EGFR in colorectal cancers and glioblastomas N Engl J Med 351 2883 Occurrence Handle15625347 Occurrence Handle10.1056/NEJM200412303512724 Occurrence Handle1:CAS:528:DC%2BD2MXhsl2isg%3D%3D
Delord JP, Beale P, Van Cutsem E, et al. A phase Ib dose-escalation trial of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer (MCRC) patients. J Clin Oncol, 2004 ASCO Annual Meeting Proceedings, 2004;22:266s:3585a
Messersmith WA, Baker SD, Dinh K, et al. Phase I trial and biologic study of Erlotinib combined with FOLFOX-4 in patients with advanced colorectal cancer: initial results. J Clin Oncol, 2004 ASCO Annual Meeting Proceedings, 2004;22:208s:3052a
Versola M, Burris HA, Jones S, et al. Clinical activity of GW572016 in EGF10003 in patients with solid tumors. J Clin Oncol, 2004 ASCO Annual Meeting Proceedings, 2004;22:206s:3047a
Schwartz G, Chu SC, Hammond LA, et al. Phase I clinical, biology and pharmacokinetic study of the combination of GW 572016 and capecitabine in patients with advanced solid tumors. J Clin Oncol, 2004 ASCO Annual Meeting Proceedings, 2004;22:212s:3070a
Tejpar S, Van Cutsem E, Gamelin E, et al. Phase 1/2a study of EKB-569,an irreversible inhibitor of epidermal growth factor receptor, in combination with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX-4) in patients with advanced colorectal cancer (CRC). J Clin Oncol, 2004 ASCO Annual Meeting Proceedings, 2004;22:264s:3579a
Casado E, Folprecht G, Paz-Ares L, et al. A phase I/IIA pharmacokinetic (PK) and serial skin and tumor pharmacodynamic (PD) study of the EGFR irreversible tyrosine kinase inhibitor EKB-569 in combination with 5-fluorouracil (5FU), leucovorin (LV) and irinotecan (CPT-11) (FOLFIRI regimen) in patients (pts) with advanced colorectal cancer (ACC). J Clin Oncol, 2004 ASCO Annual Meeting Proceedings, 2004;22:255s:3543a
Nemunaitis JJ, Eiseman I, Cunningham C, et al. A phase 1 trial of CI-1033, a pan-erbB tyrosine kinase inhibitor, given daily for 14 days every 3 weeks, in patients with advanced solid tumors. Paper presented at: American Society of Clinical Oncology Annual Meeting; May 31, 2003; Chicago, Illinois
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Overman, M.J., Hoff, P.M. EGFR-Targeted Therapies in Colorectal Cancer. Dis Colon Rectum 50, 1259–1270 (2007). https://doi.org/10.1007/s10350-007-0228-3
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DOI: https://doi.org/10.1007/s10350-007-0228-3