Cetuximab is a chimeric mouse-human monoclonal antibody to the human epidermal growth factor (EGF) receptor which is used in the treatment of metastatic colon and head and neck cancers. Cetuximab has been linked to mild and transient serum enzyme elevations during therapy, but has not been implicated in cases of clinically apparent acute liver injury.


Cetuximab (se tux’ i mab) is a chimeric mouse-human monoclonal IgG1 kappa antibody to the human epidermal growth factor (EGF) receptor which is present on many normal cell types and is overexpressed in several forms of cancer. Cetuximab has been shown to prolong survival in patients with EGF receptor expressing and wild type KRAS expressing colorectal cancer. Cetuximab has also been shown to be effective in patients with squamous cell carcinoma of the head and neck. Cetuximab was approved for use the United States in 2004 and current indications include metastatic colorectal and head and neck cancer usually in combination with other antineoplastic agents or radiation therapy. Cetuximab is available in liquid solution of 100 and 200 mg in single dose vials (2 mg/mL) under the brand name Erbitux. The recommended regimen is 400 mg/m2 by intravenous infusion initially and 250 mg/m2 weekly thereafter. Common side effects include infusion reactions (premedication with antihistamines is recommended), chills, fever, acne, skin rash, fatigue, headache and diarrhea. Less common but potentially serious side effects include severe cutaneous reactions, infections, acute renal failure, pulmonary embolus and cardiopulmonary arrest.


Publications on the large scale trials of cetuximab, rates of ALT elevations and clinically apparent liver injury were usually not mentioned. In a study of squamous cell carcinoma of the head and neck, some degree of ALT elevation was reported in 45% of persons receiving cetuximab and radiation therapy versus 22% of those receiving radiation alone, but elevations above 5 times the ULN were rare (2% vs 1%). During the initial clinical trials and subsequent to its approval and more wide scale use, there have been no published reports of cetuximab hepatotoxicity.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

The cause of the serum enzyme elevations during cetuximab therapy is not known. However, the human EGF receptor is present on many cells and some of the adverse events, including mild liver injury, may be due to a direct effect of the monoclonal antibody on cells that express EGF receptors.

Outcome and Management

The serum aminotransferase elevations that occur on cetuximab therapy are generally transient, mild and asymptomatic and do not require dose modification or delay in therapy. Elevations above 5 times the upper limit of normal should lead to more careful monitoring and discontinuation or delay in therapy until levels return to normal or near normal levels. There is no information on cross reactivity of liver injury among the different monoclonal antibodies. Panitumumab is another monoclonal antibody to EGFR that is approved for use in the United States for metastatic colorectal cancer. Panitumumab is a human monoclonal IgG2 antibody and has a similar profile of side effects to cetuximab, except for a lower rate of infusion reactions.

Drug Class: Antineoplastic Agents, Monoclonal Antibodies



Cetuximab – Erbitux®


Antineoplastic Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 03 October 2017

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    (Review of hepatotoxicity of immunosuppressive agents mentions rituximab and problems of reactivation of hepatitis B, but also states that "the biological immunosuppressants are largely free from hepatotoxicity, with the exception of the TNF alpha antagonists").
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    (Concise review of mechanism of action, clinical efficacy, and cost of bevacizumab and cetuximab, two antineoplastic monoclonal antibodies, shortly after their approval in the US; adverse effects of cetuximab include acne [which is common and can be severe], infusion reactions, asthenia, diarrhea, nausea, vomiting and abdominal pain and rarely interstitial pneumonitis; no mention of hepatotoxicity).
  • Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351 337-45. [PubMed: 15269313]
    (Among 329 patients with metastatic colorectal cancer treated with cetuximab and irinotecan or cetuximab alone, side effects included acne like rash [89%], but no mention of ALT elevations or hepatotoxicity).
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    (Among 57 patients with EGFR expressing, metastatic refractory colorectal cancer treated with cetuximab, common adverse events included acne-like skin rash [86%], fatigue [56%] and allergic reactions; no mention of ALT elevations or hepatotoxicity).
  • Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, Knecht R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol 2007; 25: 2171-7. [PubMed: 17538161]
    (Among 103 patients with metastatic or recurrent head and neck cancer treated with cetuximab, adverse events included rash, acne and fatigue, and there were 6 infusion related reactions, including one death; no mention of ALT elevations or hepatotoxicity).
  • Pinto C, Di Fabio F, Siena S, Cascinu S, Rojas Llimpe FL, Ceccarelli C, Mutri V, et al. Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol 2007; 18: 510-7. [PubMed: 17164226]
    (Among 38 patients with advanced gastric carcinoma who received FOLFIRI chemotherapy and intravenous cetuximab [weekly], adverse events include in acne in 31 [82%], hypomagnesemia in 13 [34%], and elevated ALT levels in 10 [26%] which were above 5 times ULN in 2 [5%]).
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    (Among 36 patients with colorectal cancer undergoing hepatic resection after chemotherapy, steatohepatitis was less frequent in 21 patients who received bevacizumab than matched controls [5% vs 33%], and sinusoidal obstruction syndrome was less frequent in 15 patients given cetuximab than controls [0% vs 33%]).
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    (Among 26 patients with metastatic colorectal cancer undergoing preoperative chemotherapy who also received cetuximab, serum enzyme and bilirubin elevations were similar to 26 matched control patients and liver histology showed no differences in rates of steatohepatitis, sinusoidal obstruction syndrome or fibrosis).
  • Tveit KM, Guren T, Glimelius B, Pfeiffer P, Sorbye H, Pyrhonen S, Sigurdsson F, et al. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol 2012; 30: 1755-62. [PubMed: 22473155]
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    (In a metaanalysis of results on 1970 patients from 4 controlled trials of cetuximab, severe adverse events that were more common with cetuximab were acne like rash, leucopenia, febrile neutropenia, septic events, fatigue, diarrhea and infusion reactions; no mention of ALT elevations or hepatotoxicity).
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  • Enzinger PC, Burtness BA, Niedzwiecki D, Ye X, Douglas K, Ilson DH, Villaflor VM, et al. CALGB 80403 (Alliance)/E1206: a randomized phase II study of three chemotherapy regimens plus cetuximab in metastatic esophageal and gastroesophageal junction cancers. J Clin Oncol 2016; 34: 2736-42. [PMC free article: PMC5019745] [PubMed: 27382098]
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    (Among 201 patients with recurrent or metastatic head and neck cancer treated with cetuximab and cisplatin with or without paclitaxel, the medial progression-free and overall survival were similar, and ALT or AST elevations above 5 times ULN occurred in 4.4% vs 5.0%).