Abstract
The prognosis of metastatic colorectal cancer remains poor despite advances made in recent years, particularly with new treatments directed towards molecular targets. Cetuximab, a chimeric immunoglobulin (Ig)G1 monoclonal antibody that targets the ligand-binding domain of the epidermal growth factor receptor (EGFR), is active in metastatic colorectal cancer. As an IgG1 antibody, cetuximab may exert its antitumour efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. The benefits of cetuximab in metastatic colorectal cancer are well documented in clinical trials and are acknowledged in the approval and licensing of this agent. There is evidence of the role of cetuximab not only in irinotecan-refractory or heavily pretreated patients, but also of the efficacy and safety of the addition of this agent to FOLFIRI (irinotecan/5-fluorouracil/leucovorin) in first-line metastatic colorectal cancer, with an enhanced effect in 5-fluorouracil patients with Kirsten rat sarcoma (KRAS) wild-type tumours. In these patients, a recent meta-analysis of the pooled Cetuximab Combined with Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer (CRYSTAL) and Oxaliplatin and Cetuximab in First-Line Treatment of mCRC (OPUS) patient populations confirms that the addition of cetuximab to first-line chemotherapy achieves a statistically significant improvement in the best overall response, overall survival time, and progression-free survival (PSF) compared with chemotherapy alone. In nonresectable colorectal liver metastases, cetuximab plus FOLFOX-6 (oxaliplatin/5-fluorouracil/leucovorin) or cetuximab plus FOLFIRI increased significantly resectability of liver metastases, including R0 resections. Also, preliminary data indicate that cetuximab can be administered in a more convenient 2-week schedule in combination with standard chemotherapy. Cetuximab is generally well tolerated. Acne-form rash is the most frequent toxicity. Up to the present time, the results obtained with targeted therapy combinations are not as encouraging as initially expected. The identification of biomarkers associated with disease control, including KRAS and BRAF mutation status in patients treated with cetuximab, is changing the current management of metastatic colorectal cancer. Clinical and molecular predictive markers of response are under active evaluation in order to better select patients who could benefit from cetuximab treatment, with the aim of both optimising patient outcomes and avoiding unnecessary toxicities.
Similar content being viewed by others
References
Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108
National Comprehensive Cancer Network (2009) NCCN clinical practice guidelines in oncology™. Colon cancer. V.2.2009. Available at http://www.nccn.org
Boyle P, Ferlay J (2005) Cancer incidence and mortality in Europe, 2004. Ann Oncol 16:481–488
Center MM, Jemal A, Ward E (2009) International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev 18:1688–1694
Ribes J, Navarro M, Cèries R et al (2009) Colorectal cancer mortality in Spain: trends and projections for 1985–2019. Eur J Gastroenterol Hepatol 21:92–100
Field K, Lipton L (2007) Metastatic colorectal cancer — past, progress and future World J Gastroenterol 13:3806–3815
Jemal A, Murray T, Ward E et al (2005) Cancer statistics, 2005. CA Cancer J Clin 55:10–30
Borner MM (1999) Neoadjuvant chemotherapy for unresectable liver metastases of colorectal cancer — too good to be true? Ann Oncol 10:623–626
Kremeny B (2006) Management of liver metastases from colorectal cancer. Oncology 20:1161–1176
Muratore A, Zorzi D, Bouzari H et al (2007) Asymptomatic colorectal cancer with un-resectable liver metastases: immediate colorectal resection or up-front systemic chemotherapy? Ann Surg Oncol 14:766–770
Hammoud MA, McCutcheon IE, Elsouki R et al (1996) Colorectal carcinoma and brain metastasis: distribution, treatment, and survival. Ann Surg Oncol 3:453–463
Pestieau SR, Sugarbaker PH (2000) Treatment of primary colon cancer with peritoneal carcinomatosis. Comparison of concomitant vs. delayed management. Dis Colon Rectum 43:1341–1346
Chau I, Allen MJ, Cunningham D et al (2004) The value of routine serum carcino-embryonic antigen measurement and computed tomography in the surveillance of patients after adjuvant chemotherapy for colorectal cancer. J Clin Oncol 22:1420–1429
Desch CE, Benson AB 3rd, Somerfield MR et al (2005) Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guidelines. J Clin Oncol 23:8512–8519
Wiering B, Vogel WV, Ruers TJ, Oyen WJ (2008) Controversies in the management of colorectal liver metastases: role of PET and PET/CT. Dig Surg 25:413–420
Ogunbiyi OA, Flanagan FL, Dehdashti F et al (1997) Detection of recurrent and metastatic colorectal cancer: comparison of positron emission tomography and computed tomography. Ann Surg Oncol 4:613–620
de Geus-Oei LF, Ruers TJ, Punt CJ et al (2006) FDG-PET in colorectal cancer. Cancer Imaging 6: S71–S81
de Geus-Oei LF, Vriens D, van Laarhoven HW et al (2009) Monitoring and predicting response to therapy with 18F-FDG PET in colorectal cancer: a systematic review. J Nucl Med 50(Suppl 1):43S–54S
Tobaruela E, Enriquez JM, Diez M et al (1997) Evaluation of serum carcinoembryonic antigen monitoring in the follow-up of colorectal cancer patients with metastatic lymph nodes and a normal preoperative serum level. Int J Biol Markers 12:18–21
Graboń W, Mielczarek-Puta M, Chrzanowskaa A, Barańczyk-Kuźma A (2009) l-Arginine as a factor increasing arginase significance in diagnosis of primary and metastatic colorectal cancer. Clin Biochem 42:353–357
Levine PH, Joutovsky A, Cangiarella J et al (2006) CDX-2 expression in pulmonary fineneedle aspiration specimens: a useful adjunct for the diagnosis of metastatic colorectal adenocarcinoma. Diagn Cytopathol 34:191–195
Kelly H, Goldberg RM (2005) Systemic therapy for metastatic colorectal cancer: current options, current evidence. J Clin Oncol 23:4553–4560
González HD, Figueras J (2007) Practical questions in liver metastases of colorectal cancer: general principles of treatment. HPB (Oxford) 9: 251–258
Erturk SM, Ichikawa T, Fujii H et al (2006) PET imaging for evaluation of metastatic colorectal cancer of the liver. Eur J Radiol 58:229–235
Nuzzo G, Giuliante F, Ardito F et al (2008) Influence of surgical margin on type of recurrence after liver resection for colorectal metastases: a single-center experience. Surgery 143:384–393
Simmonds PC, Primrose JN, Colquitt JL et al (2006) Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies. Br J Cancer 94:982–999
Viganò L, Ferrero A, Lo Tesoriere R, Capussotti L (2008) Liver surgery for colorectal metastases: results after 10 years of follow-up. Long-term survivors, late recurrences, and prognostic role of morbidity. Ann Surg Oncol 15:2458–2464
Laurent C, Sa Cunha A, Rullier E et al (2004) Impact of microscopic hepatic lymph node involvement on survival after resection of colorectal liver metastasis. J Am Coll Surg 198:884–891
Masi G, Loupakis F, Pollina L et al (2009) Long-term outcome of initially unresectable metastatic colorectal cancer patients treated with 5-fluorouracil/leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) followed by radical surgery of metastases. Ann Surg 249:420–425
Masi G, Cupini S, Marcucci L et al (2006) Treatment with 5-fluorouracil/folinic acid, oxaliplatin, and irinotecan enables surgical resection of metastases in patients with initially unresectable metastatic colorectal cancer. Ann Surg Oncol 13: 58–65
Teng LS, Zheng Y, Zhang J (2008) Neoadjuvant chemotherapy for metastatic colorectal cancer to the liver: from chemotherapy to targeting therapy. Hepatobiliary Pancreat Dis Int 6:569–570
Aloia T, Sebagh M, Plasse M et al (2006) Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. J Clin Oncol 24:4983–4990
Goldberg RM, Rothenberg ML, Van Cutsem E et al (2007) The continuum of care: a paradigm for the management of metastatic colorectal cancer. Oncologist 12:38–50
Van Cutsem E, Hoff PM, Harper P et al (2004) Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials. Br J Cancer 90:1190–1197
de Gramont A, Figer A, Seymour M et al (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938–2947
Hochster HS, Hart LL, Ramanathan RK et al (2006) Safety and efficacy of oxaliplatin/fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC): Final analysis of the TREE-Study. J Clin Oncol 24(Suppl):3510
Fuchs C, Marshall J, Mitchell E et al (2006) A randomized trial of first-line irinotecan/fluoropyrimidine combinations with or without celecoxib in metastatic colorectal cancer (BICC-C). J Clin Oncol 24(Suppl):3506
Saltz LB, Cox JV, Blanke C et al (2000) Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 343:905–914
Douillard JY, Cunningham D, Roth AD et al (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355:1041–1047
Tournigand C, André T, Achille E et al (2004) FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 22:229–237
Goldberg RM, Sargent DJ, Morton RF et al (2004) A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 22:23–30
Colucci G, Gebbia V, Paoletti G et al (2005) Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell’Italia Meridionale. J Clin Oncol 23:4866–4875
Souglakos J, Androulakis N, Syrigos K et al (2006) FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicentre randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer 94:798–805
Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:335–2342
Cunningham D, Humblet Y, Siena S et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345
Rothenberg ML, Cox JV, Butts C et al (2008) Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study. Ann Oncol 19:1720–1726
Cassidy J, Clarke S, Díaz-Rubio E et al (2008) Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 26:2006–2012
Porschen R, Arkenau HT, Kubicka S et al (2007) Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol 25:4217–4223
Díaz-Rubio E, Tabernero J, Gómez-España A et al (2007) Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial. J Clin Oncol 25:4224–4230
Delaunoit T, Goldberg RM, Sargent DJ et al (2004) Mortality associated with daily bolus 5-fluorouracil/leucovorin administered in combination with either irinotecan or oxaliplatin. Cancer 101:2170–2176
Goldberg R (2006) Therapy for metastatic colorectal cancer. Oncologist 11:981–987
Arnold D, Siewczynski R, Schmoll HJ (2006) The integration of targeted agents into systemic therapy of metastatic colorectal cancer. Ann Oncol 17(Suppl 10):122–128
Köhne CH, Lenz HJ (2009) Chemotherapy with targeted agents for the treatment of metastatic colorectal cancer. Oncologist 14:478–488
Rodriguez J, Zarate R, Bandres E et al (2007) Combining chemotherapy and targeted therapies in metastatic colorectal cancer. Word J Gastroenterol 13:5867–5876
Lee JC, Chow NH, Wang ST, Huang SM (2000) Prognostic value of vascular endothelial growth factor expression in colorectal cancer patients. Eur J Cancer 36:748–753
Kabbinavar F, Hurwitz HI, Fehrenbacher L et al (2003) Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2:60–65
Hurwitz HI, Fehrenbacher L, Hainsworth JD et al (2006) Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer. J Clin Oncol 23:3502–3508
Giantonio BJ, Catalano PJ, Meropol NJ et al (2007) 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 25:1539–1544
Saltz L, Clarke S, Diaz-Rubio E et al (2008) Bevacizumab (Bev) in combination with XELOX or FOLFOX4: updated efficacy results from XELOX-1/NO16966, a randomized phase III trial in first-line metastatic colorectal cancer. J Clin Oncol 26:2013–2019
Sobrero A, Ackland S, Clarke S et al (2009) Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. Oncology 77:113–119
Van Cutsem E, Rivera F, Berry S et al (2009) Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol. doi:10.1093/annonc/mdp233
Cao Y, Tan A, Gao F et al (2009) A meta-analysis of randomized controlled trials comparing chemotherapy plus bevacizumab with chemotherapy alone in metastatic colorectal cancer. Int J Colorectal Dis 24:677–695
Porebska I, Harlozińska A, Bojarowski T (2000) Expression of the tyrosine kinase activity growth factor receptors (EGFR, ERB B2, ERB B3) in colorectal adenocarcinomas and adenomas. Tumor Biol 21:105–115
Saltz I, Rubin M, Hochster H et al (2001) Cetuximab (IMC-C225) plus irinotecan (CPT-11) is active in CPT-11 refractory colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR). Proc Am Soc Clin Oncol 20. Abstract 7
Cunningham D, Humblet Y, Siena S et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345
Vincenzi B, Santini D, Rabitti C et al (2006) Cetuximab and irinotecan as third-line therapy in advanced colorectal cancer patients: a single centre phase II trial. Br J Cancer 94:792–797
Gebbia V, Del Prete S, Borsellino N et al (2006) Efficacy and safety of cetuximab/irinotecan in chemotherapy-refractory metastatic colorectal adenocarcinomas: a clinical practice setting, multicenter experience. Clin Colorectal Cancer 5: 422–428
Sobrero AF, Maurel J, Fehrenbacher L et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26:2311–2319
Wilke H, Glynne-Jones R, Thaler J et al (2008) Cetuximab plus irinotecan in heavily pretreated metastatic colorectal cancer progressing on irinotecan: MABEL Study. J Clin Oncol 26:5335–5343
Folprecht G, Lutz MP, Schöffski P et al (2006) 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 17:450–456
Raoul JL, Van Laethem JL, Peeters M et al (2009) Cetuximab in combination with irinotecan/5-fluorouracil/folinic acid (FOLFIRI) in the initial treatment of metastatic colorectal cancer: a multicentre two-part phase I/II study. BMC Cancer 9:112
Arnold D, Höhler T, Dittrich C et al (2008) Cetuximab in combination with weekly 5-fluorouracil/folinic acid and oxaliplatin (FUFOX) in untreated patients with advanced colorectal cancer: a phase Ib/II study of the AIO GI Group. Ann Oncol 19: 1442–1449
Van Cutsem E, Köhne CH, Hitre E et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408–1417
Bokemeyer C, Bondarenko I, Makhson A et al (2009) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27:663–671
Maiello E, Giuliani F, Gebbia V et al (2007) Cetuximab: clinical results in colorectal cancer. Ann Oncol 18Suppl 6:vi8–vi10
Wong SF (2005) Cetixumab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. Clin Ther 27:684–694
Barnett D, Stevens A, Longson C (2006) Appraisal of bevacizumab and cetuximab for treatment of metastatic colorectal cancer in the UK. Lancet Oncol 7:807–808
Peeters M, Price T, Van Laethem JL (2009) Antiepidermal growth factor receptor monotherapy in the treatment of metastatic colorectal cancer: where are we today? Oncologist 14:29–39
Wainberg Z, Hecht JR (2006) Panitumumab in colon cancer: a review and summary of ongoing trials. Expert Opin Biol Ther 6:1229–1235
Wu M, Rivkin A, Pham T (2008) Panitumumab: human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal cancer. Clin Ther 30:14–30
Li S, Schmitz KR, Jeffrey PD et al (2005) Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. Cancer Cell 7: 301–311
Saltz LB, Meropol NJ, Loehrer PJ Sr et al (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. N Engl J Med 343:905–914
Lenz HJ, Van Cutsem E, Khambata-Ford S et al (2006) Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol 24:4914–4921
Souglakos J, Kalykaki A, Vamvakas L et al (2007) Phase II trial of capecitabine and oxaliplatin (CAPOX) plus cetuximab in patients with metastatic colorectal cancer who progressed after oxaliplatin-based chemotherapy. Ann Oncol 18:305–310
Lenz HF (2007) Cetuximab in the management of colorectal cancer. Biologics 1:77–91
Jonker DJ, Karapetis CS, Moore M et al (2007) Randomized phase III trial of cetuximab monotherapy plus best supportive care [BSC] versus BSC Alone in patients with pretreated metastatic epidermal growth factor receptor [EGFR]-positive colorectal carcinoma: a trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) and the Australasian Gastro-Intestinal Trials Group (AGITG). Proc Am Assoc Cancer Res. Abstract LB-1
Sobrero AF, Fehrenbacher L, Rivera F et al (2007) Randomized phase III trial of cetuximab plus irinotecan versus irinotecan alone for metastatic colorectal cancer in 1298 patients who have failed prior oxaliplatin-based therapy: the EPIC trial. Proc Am Assoc Cancer Res. Abstract LB-2
Folprecht G, Gruenberger T, Hartmann JT et al (2009) Cetuximab plus FOLFOX6 or cetuximab plus FOLFIRI as neoadjuvant treatment of nonresectable colorectal liver metastases: a randomized multicenter study (CELIM-study). 2009 ASCO Annual Meeting, Gastrointestinal Cancers Symposium. Abstract 296
Bechstein WO, Lang H, Köhne C et al (2009) Resectability and agreement between surgeons: Review of CT and MR scan of the CELIM study: (Multicenter randomized trial of cetuximab/FOLFOX versus cetuximab/FOLFIRI in unresectable liver metastases. J Clin Oncol 27:15 (Suppl). Abstract 4091.
Macarulla T, Ramos J Élez E, Capdevila J et al (2008) Update on novel strategies to optimize cetuximab therapy in patients with metastatic colorectal cancer. Clin Colorectal Cancer 7:300–308
Saltz LB, Lenz HJ, Kindler HL et al (2007) Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. J Clin Oncol 25:4557–4561
Tol J, Koopman M, Cats A et al (2009) Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med 360:563–572
Simi L, Prateso N, Vignoli M et al (2008) High resolution melting analysis for rapid detection of KRAS, BRAF, and PIK3CA gene mutations in colorectal cancer. Am J Clin Pathol 130:247–253
Khambata-Ford S, Garrett CR, Meropol NJ et al (2007) Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 25:3230–3237
van Krieken JH, Jung A, Kirchner T et al (2008) KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program. Virchow Arch 453:417–431
Linardou H, Dahabreh IJ, Kanaloupiti D et al (2008) Assessment of somatic K-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol 9:962–972
Amado RG, Wolf M, Peeters M et al (2008) Wildtype KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26:1626–1634
Lièvre A, Bachet JB, Boige V et al (2008) KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Cin Oncol 26:374–379
Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F et al (2007) Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 67:2643–2648
De Roock W, Piessevaux H, De Schutter J et al (2008) KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab. Ann Oncol 19:508–515
Finocchiaro G, Cappuzzo F, Jänne PA et al (2007) EGFR, HER2 and Kras as predictive factors for cetuximab sensitivity in colorectal cancer. J Clin Oncol 2007 ASCO Annual Meeting Proceedings 25(Suppl): 4021
Di Fiore F, Blanchard F, Charbonnier F et al (2007) Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy. Br J Cancer 23: 1166–1169
Lièvre A, Bachet JB, Le Corre D et al (2006) KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res 66:3992–3995
Cervantes A, Macarulla T, Martinelli E et al (2008) Correlation of KRAS status (wild type [wt] vs. mutant [mt]) with efficacy to first-line cetuximab in a study of cetuximab single agent followed by cetuximab + FOLFIRI in patients (pts) with metastatic colorectal cancer (mCRC). J Clin Oncol 26(Suppl). Abstract 4129
Van Cutsem E, Lang I, D’haens G et al (2008) KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: The CRYSTAL experience. J Clin Oncol 26(Suppl). Abstract 2
Karapetis CS, Khambata-Ford S, Jonker DJ et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359:1757–1765
Bokemeyer C, Bondarenko I, Hartmann JT et al (2008) KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: The OPUS experience. J Clin Oncol 26(Suppl). Abstract 4000
Punt CJ, Tol J, Rodenburg CJ et al (2008) Randomized phase III study of capecitabine, oxaliplatin, and bevacizumab with or without cetuximab in advanced colorectal cancer (ACC), the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). J Clin Oncol 26(Suppl). Abstract LBA4011
Winer E, Gralow J, Diller L et al (2009) Clinical cancer advances 2008: major research advances in cancer treatment, prevention, and screening-a report from the American Society of Clinical Oncology. J Clin Oncol 27:812–816
Allegra CJ, Jessup JM, Somerfield MR et al (2009) American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to antiepidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 27:2091–2096
National Comprehensive Cancer Network (2010) NCCN clinical practice guidelines in colon/rectal cancer. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp Accessed March 8, 2010
Schlaeth M, Berger S, Derer S, Klausz K, Lohse S, Dechant M et al (2010) Fc-engineered EGF-R antibodies mediate improved antibody-dependent cellular cytotoxicity (ADCC) against KRAS-mutated tumor cells. Cancer Sci 101:1080–1088
Bibeau F, Lopez-Crapez E, Di Fiore F et al (2009) Impact of Fc{gamma}RIIa-Fc{gamma}RIIIa polymorphisms and KRAS mutations on the clinical outcome of patients with metastatic colorectal cancer treated with cetuximab plus irinotecan. J Clin Oncol 27:1122–1129
Van Cutsem E, Lang I, Folprecht G et al (2010) 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. ASCO 2010. Gastrointestinal Cancers Symposium. Abstract 281
Bokemeyer C, Bondarenko I, Hartmann JT et al (2010) Biomarkers predictive for outcome in patients with metastatic colorectal cancer (mCRC) treated with first-line FOFOX4 plus or minus cetuximab: updated data from the OPUS study. ASCO 2010. Gastrointestinal Cancers Symposium. Abstract 428
Kohne C, Rougier P, Stroh C et al (2010) Cetuximab with chemotherapy (CT) as first-line treatment for metastatic colorectal cancer (mCRC): a meta-analysis of the CRYSTAL and OPUS studies according to KRAS and BRAF mutation status. ASCO 2010. Gastrointestinal Cancers Symposium. Abstract 406
Tsiatis AC, Norris-Kirby A, Rich RG et al (2009) Comparison of Sanger sequencing, pyrosequencing, and melting curve analysis for the detection of KRAS mutations. Diagnostic and clinical implications. J Mol Diagn doi:10.2353/jmoldx.2010.090188
Weichert W, Schewe C, Lehmann A et al (2010) KRAS genoty** of paraffin-embedded colorectal cancer tissue in routine diagnostics: comparison of methods and impact of histology. J Mol Diagn 12:35–42
Zuo Z, Chen SS, Chandra PK et al (2009) Application of COLD-PCR for improved detection of KRAS mutations in clinical samples. Mod Pathol 22:1023–1031
Franklin WA, Haney J, Sugita M (2010) KRAS mutation: comparison of testing methods and tissue sampling techniques in colon cancer. J Mol Diagn 12:43–50
Su X, Lacouture ME, Jia Y, Wu S (2009) Risk of high-grade skin rash in cancer patients treated with cetuximab—an antibody against epidermal growth factor receptor: systemic review and metaanalysis. Oncology 77:124–133
Bernier J, Bonner J, Vermorken JB et al (2008) Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy and EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck. Ann Oncol 19:142–149
Folprecht G, Nowacki M, Lang I et al (2009) Cetuximab plus FOLFIRI first line in patients (pts) with metastatic colorectal cancer (mCRC): a quality-of-life (QoL) analysis of the CRYSTAL trial. J Clin Oncol 27:15s (Suppl). Abstract 4076
Siena S, Glynne-Jones R, Thaler J et al (2007) MABEL — A large multinational study of cetuximab plus irinotecan in irinotecan-resistant metastatic colorectal cancer: Update on infusion related reactions (IRR). ASCO 2007. Gastrointestinal Cancers Symposium. Abstract 353
Fakih MG, Wilding G, Lombardo J (2006) Cetuximab-induced hypomagnesemia in patients with colorectal cancer. Clin Colorectal Cancer 6:152–156
Vincenzi B, Santini D, Galluzzo S et al (2008) Early magnesium reduction in advanced colorectal cancer patients treated with cetuximab plus irinotecan as predictive factor of early efficacy and outcome. Clin Cancer Res 14:4219. doi:10.1158/1078-0432
Au HJ, Karapetis CS, O’Callaghan CJ et al (2009) Health-related quality of life in patients with advanced colorectal cancer treated with cetuximab: overall and KRAS-specific results of the NCIC CTG and AGITG CO.17 Trial. J Clin Oncol 27: 1822–1828
Ramanathan RK (2008) Alternative dosing schedules for cetuximab: a role for biweekly administration? Clin Colorectal Cancer 7:364–368
Mrabti H, De la Fouchardiere C, Desseigne F et al (2009) Irinotecan associated with cetuximab given every 2 weeks versus cetuximab weekly in metastatic colorectal cancer. J Cancer Res Ther 5: 272–276
Tabernero J, Pfeiffer P, Cervantes A (2008) Administration of cetuximab every 2 weeks in the treatment of metastatic colorectal cancer: an effective, more convenient alternative to weekly administration? Oncologist 13:113–119
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
García-Foncillas, J., Díaz-Rubio, E. Progress in metastatic colorectal cancer: growing role of cetuximab to optimize clinical outcome. Clin Transl Oncol 12, 533–542 (2010). https://doi.org/10.1007/s12094-010-0551-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12094-010-0551-3