{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T10:19:01Z","timestamp":1769336341059,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"vor","delay-in-days":1314,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p>Treatment of metastatic colorectal disease has evolved over the last decade. Two epidermal growth factor receptor (EGFR) monoclonal antibodies\u2014cetuximab and panitumumab\u2014have been developed in an effort to provide yet another therapeutic option. The EGFR is a transmembrane glycoprotein, expressed constitutively throughout the body and found on many epithelial tissues. The monoclonal antibodies bind to and inhibit the activation of the receptor in the body. This inhibition prevents tumor cell growth, angiogenesis, invasion, and metastasis, and induces apoptosis. Cetuximab and panitumumab exhibit nonlinear pharmacokinetics. Both monoclonal antibodies are approved for the treatment of refractory metastatic colorectal cancer. Cetuximab in combination with irinotecan has significantly better response rates and progression\u2010free survival compared with those of cetuximab or irinotecan alone. Cetuximab and panitumumab as monotherapy have shown significantly better response rates and progression\u2010free survival compared with best supportive care in patients refractory to irinotecan and oxaliplatin. In the Cetuximab Combined with Irinotecan in First Line Therapy for Metastatic Colorectal Cancer (CRYSTAL) trial, treatment\u2010na\u00efve patients received cetuximab in combination with the chemotherapy regimen infusional leucovorin, fluorouracil, and irinotecan (FOLFIRI) or FOLFIRI alone; the difference in progression\u2010free survival was statistically significant but suggested only a modest benefit over FOLFIRI alone (8.9 vs 8 mo, p=0.036). Results of a preplanned analysis of the first 231 events in the Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) trial favored the control group (chemotherapy regimen with folinic acid [leucovorin], fluorouracil, and oxaliplatin [FOLFOX] plus bevacizumab) instead of the control group plus panitumumab. For clinical consideration, many trials have shown that the intensity or absence of EGFR expression is not a clinically significant predictor of outcomes. Development and intensity of a rash are suggested to be a positive predictor of outcomes in patients. The most common adverse events of EGFR monoclonal antibody therapy are rash, diarrhea, and hypomagnesemia. Other serious but not common adverse events include hypersensitivity reactions and pulmonary toxicity. The availability of EGFR monoclonal antibodies has provided another weapon in the arsenal to treat refractory metastatic colorectal cancer. They have shown safety and efficacy in combination with other chemotherapy regimens and as monotherapy; however, their use as metastatic colorectal cancer therapy needs to be further explored.<\/jats:p>","DOI":"10.1592\/phco.28.6.742","type":"journal-article","created":{"date-parts":[[2008,5,27]],"date-time":"2008-05-27T07:39:22Z","timestamp":1211873962000},"page":"742-754","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Epidermal Growth Factor Receptor Monoclonal Antibodies for the Treatment of Metastatic Colorectal Cancer"],"prefix":"10.1002","volume":"28","author":[{"given":"Gary W.","family":"Jean","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachin R.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,1,6]]},"reference":[{"key":"e_1_2_1_2_2","volume-title":"Cancer facts and figures 2007","author":"American Cancer Society","year":"2007"},{"issue":"16","key":"e_1_2_1_3_2","first-page":"3501","article-title":"Oxaliplatin\/5FU\/LV in the adjuvant treatment of stage II and stage III colon cancer: efficacy results with a median follow\u2010up of 4 years [abstract]","volume":"23","author":"Gramont A","year":"2005","journal-title":"J Clin Oncol (2005 ASCO annual meeting proceedings)"},{"key":"e_1_2_1_4_2","volume-title":"Cancer facts and figures 2006","author":"American Cancer Society","year":"2006"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032691"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.6-1-81"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.09.046"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2004.01.002"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22133"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200464010-00007"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200666110-00003"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200666150-00011"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001622-200111000-00014"},{"key":"e_1_2_1_14_2","volume-title":"Vectibix (panitumumab) package insert","author":"Amgen","year":"2006"},{"key":"e_1_2_1_15_2","volume-title":"Erbitux (cetuximab) package insert","author":"ImClone Systems Incorporated, Bristol\u2010Myers Squibb","year":"2006"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/85.16.1327"},{"key":"e_1_2_1_17_2","first-page":"909","article-title":"Antitumor activity of sequential treatment with topotecan and anti\u2010epidermal growth factor receptor monoclonal antibody c225","volume":"5","author":"Ciardiello F","year":"1999","journal-title":"Clin Cancer Res"},{"key":"e_1_2_1_18_2","first-page":"994","article-title":"Enhanced antitumor activity of anti\u2010epidermal growth factor receptor monoclonal antibody IMC\u2010C225 in combination with irinotecan (CPT\u201011) against human colorectal tumor xenografts","volume":"8","author":"Prewett MC","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.4.904"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0958-1669(02)00348-8"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.11.061"},{"issue":"18","key":"e_1_2_1_22_2","first-page":"4133","article-title":"Simplification of cetuximab administration: double dose every second week as a 60 minute infusion [abstract]","volume":"25","author":"Pfeiffer P","year":"2007","journal-title":"J Clin Oncol (2007 ASCO annual meeting proceedings)"},{"key":"e_1_2_1_23_2","first-page":"LB","volume-title":"Optimal dose of cetuximab administered every 2 weeks (q2w): a phase I safety, pharmacokinetics (PK) and pharmacodynamics (PD) study of weekly (q1w) and q2w schedules in patients (pts) with metastatic colorectal cancer (mCRC) [abstract]","author":"Cervantes A","year":"2007"},{"key":"e_1_2_1_24_2","first-page":"1337","article-title":"In vivo disposition of irinotecan (cpt\u201011) and its metabolites in combination with the monoclonal antibody cetuximab","volume":"26","author":"Ettlinger DE","year":"2006","journal-title":"Anticancer Res"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.3816\/CCC.2007.n.011"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033025"},{"key":"e_1_2_1_27_2","first-page":"LB","volume-title":"Randomized phase III trial of cetuximab plus irinotecan versus irinotecan alone for metastatic colorectal cancer in 1298 patients who have failed prior oxaliplatin\u2010based therapy: the EPIC trial [abstract]","author":"Sobrero AF","year":"2007"},{"key":"e_1_2_1_28_2","first-page":"LB\u20101","volume-title":"Randomized phase III trial of cetuximab monotherapy plus best supportive care (BSC) versus BSC alone in patients with pretreated metastatic epidermal growth factor (EGFR)\u2010positive colorectal carcinoma: a trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) and the Australasian Gastro\u2010Intestinal Trials Group (AGITG) [abstract]","author":"Jonker DJ","year":"2007"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603018"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.10.182"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.7595"},{"issue":"18","key":"e_1_2_1_32_2","first-page":"3549","article-title":"MABEL: a large multinational study of cetuximab plus irinotecan in irinotecan resistant metastatic colorectal cancer [abstract]","volume":"24","author":"Wilke H","year":"2006","journal-title":"J Clin Oncol (2006 ASCO annual meeting proceedings)"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.08.1620"},{"issue":"18","key":"e_1_2_1_34_2","first-page":"3558","article-title":"Cetuximab in combination with irinotecan\/5\u2010fluorouracil (5\u2010FU)\/folinic acid (FA) (FOLFIRI) in second and third line treatment of metastatic colorectal cancer (mCRC): safety and efficacy analysis [abstract]","volume":"24","author":"Smith DM","year":"2006","journal-title":"J Clin Oncol (2006 ASCO annual meeting proceedings)"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.0949"},{"issue":"16","key":"e_1_2_1_36_2","first-page":"3574","article-title":"Erbitux (cetuximab) plus FOLFOX for colorectal cancer (EXPLORE): preliminary efficacy analysis of a randomized phase III trial [abstract]","volume":"23","author":"Jennis A","year":"2005","journal-title":"J Clin Oncol (2005 ASCO annual meeting proceedings)"},{"issue":"18","key":"e_1_2_1_37_2","first-page":"4000","article-title":"Randomized phase III study of irinotecan and 5\u2010FU\/LA with or without cetuximab in the first\u2010line treatment of patients with metastatic colorectal cancer (mCRC): the CRYSTAL trial [abstract]","volume":"25","author":"Cutsem E","year":"2007","journal-title":"J Clin Oncol (2007 ASCO annual meeting proceedings)"},{"key":"e_1_2_1_38_2","volume-title":"Amgen discontinues Vectibix treatment in PACCE trial evaluating Vectibix as part of triple combination regimen [press release]","year":"2007"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.07.113"},{"key":"e_1_2_1_40_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.0928"},{"key":"e_1_2_1_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603011"},{"key":"e_1_2_1_42_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.6305"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdj084"},{"key":"e_1_2_1_44_2","article-title":"XELIRI plus cetuximab versus XELOX plus cetuximab for first\u2010line therapy of metastatic colorectal cancer (CRC): a randomized trial of the AIO CRC study group [abstract]","author":"Heinemann V","year":"2007","journal-title":"J Clin Oncol"},{"issue":"18","key":"e_1_2_1_45_2","first-page":"4075","article-title":"Phase II trial of FOLFOX6, becacizumab and cetuximab in patients with colorectal cancer [abstract]","volume":"25","author":"Ocean AJ","year":"2007","journal-title":"J Clin Oncol (2007 ASCO annual meeting proceedings)"},{"key":"e_1_2_1_46_2","author":"ClinicalTrials.gov","year":"2007","journal-title":"Clinical trials"},{"key":"e_1_2_1_47_2","first-page":"452","article-title":"CALGB\/SWOG 80405: a phase III trial of FOLFIRI or FOLFOX with bevacizumab or cetuximab or both for untreated metastatic adenocarcinoma of the colon or rectum","volume":"4","author":"Cancer and Leukemia Group B, Southwest Oncology Group","year":"2006","journal-title":"Clin Adv Hematol Oncol"},{"key":"e_1_2_1_48_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.11-9-1010"},{"key":"e_1_2_1_49_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.08.037"},{"key":"e_1_2_1_50_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.05.0450"},{"issue":"18","key":"e_1_2_1_51_2","first-page":"4134","article-title":"Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer (mCRC): a pooled analysis of five clinical trials [abstract]","volume":"25","author":"Berlin J","year":"2007","journal-title":"J Clin Oncol (2007 ASCO annual meeting proceedings)"},{"key":"e_1_2_1_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji242"},{"key":"e_1_2_1_53_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.057"},{"issue":"16","key":"e_1_2_1_54_2","first-page":"3655","article-title":"Hypomagnesemia in patients with stage IV colorectal cancer treated with cetuximab as a single agent [abstract]","volume":"23","author":"Carson EJ","year":"2005","journal-title":"J Clin Oncol (2005 ASCO annual meeting proceedings)"},{"key":"e_1_2_1_55_2","doi-asserted-by":"publisher","DOI":"10.3816\/CCC.2006.n.033"},{"issue":"18","key":"e_1_2_1_56_2","first-page":"3556","article-title":"Cetuximab plus irinotecan for metastatic colorectal cancer (mCRC): safety analysis of 800 patients in a randomized phase III trial (EPIC) [abstract]","volume":"24","author":"Abubakr Y","year":"2006","journal-title":"J Clin Oncol (2006 ASCO annual meeting proceedings)"},{"key":"e_1_2_1_57_2","doi-asserted-by":"publisher","DOI":"10.3816\/CCC.2007.n.019"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1592%2Fphco.28.6.742","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1592\/phco.28.6.742","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T17:06:18Z","timestamp":1761066378000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1592\/phco.28.6.742"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6]]},"references-count":56,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2008,6]]}},"alternative-id":["10.1592\/phco.28.6.742"],"URL":"https:\/\/doi.org\/10.1592\/phco.28.6.742","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6]]},"assertion":[{"value":"2012-01-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}