In many cancers, including colorectal cancer, EGFR is often inappropriately activated, leading to uncontrolled cell growth. Erbitux®, a member of the class of drugs called monoclonal antibodies, has been developed specifically to block EGFR, thereby blocking tumor growth and inducing tumor regression.
Erbitux (cetuximab) is an IgG1 monoclonal antibody which, like the naturally occurring antibodies circulating as part of the body’s immune system, specifically targets and locks on to a particular target – in this case, EGFR. Erbitux® works in several ways:
- It attaches itself directly to EGFR and prevents it from becoming active.
- EGFR with Erbitux® attached is drawn inside the cell and destroyed, thereby reducing the amount of EGFR on the cell surface which could be activated.
- Since it is an antibody, Erbitux® has the ability to bring tumor cells to the attention of the immune system, which can then kill them (ADCC).
As a monoclonal antibody, the mode of action of Erbitux® is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth.
The most commonly reported side effect with Erbitux® is an acne-like skin rash that seems to be correlated with a good response to therapy.¹ In approximately five percent of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe. A premedication (corticosteroids, antihistamines) may reduce infusion-related reactions to about 1%.²
Clinical trials have shown that Erbitux® is active in combination with standard chemotherapies, such as irinotecan, oxaliplatin and cisplatin.
Erbitux® is approved in countries all over the world for treating patients with:
- metastatic colorectal cancer (mCRC) in combination with irinotecan after failure of irinotecan-based therapy
- locally advanced squamous cell carcinoma of the head and neck (SCCHN) in combination with radiation therapy.
Erbitux® is also approved in selected countries for single-agent use in both indications.
Additional links:
¹ Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus
irinotecan in irinotecan-refractory metastatic colorectal cancer.
N Engl J Med 2004; 351:337– 45.
Saltz L, Meropol NJ, Loehrer PJ, Needle M, Kopit J, Mayer RJ. Phase II trial of cetuximab
in patients with refractory colorectal cancer that expresses the epidermal growth factor
receptor. J Clin Oncol 2004; 22:1201–08.
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). Proc Am Soc Clin Oncol 2001; 20:Abstract 7 and data on file
Merck KGaA.
Herbst RS, Arquette M, Shin DM, et al. Epidermal growth factor receptor antibody
cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma
head and neck: a phase II, multicenter study. J Clin Oncol 2005; 23:In press.
Xiong HQ, Rosenberg A, LoBuglio A, et al. Cetuximab, a monoclonal antibody targeting
the epidermal growth factor receptor, in combination with gemcitabine for advanced
pancreatic cancer: a multicenter phase II Trial. J Clin Oncol 2004; 22:2610–6.
Gustafson NF, Saltz L, Cunningham D, Lenz H, Humphrey R, Adegbile IA. Safety profile
of cetuximab in patients with metastatic colorectal cancer. ASCO Gastrointestinal
Cancers Symposium 2004:Abstract 237. Virtual presentation: www.asco.org.
Saltz L, Kies M, Abbruzzese JL, Azarnia N, Needle M. The presence and intensity of the
cetuximab-induced acne-like rash predicts increased survival in studies across multiple
malignancies. Proc Am Soc Clin Oncol 2003; 22:Abstract 817.
Van Cutsem E, Mayer RJ, Gold P, et al. Correlation of acne rash and tumor response with
cetuximab monotherapy in patients with colorectal cancer refractory to both irinotecan
and oxaliplatin. EORTC-NCI-AACR Symposium 2004:Abstract 279.
² MABEL – a large multinational study of cetuximab plus irinotecan in irinotecan-resistant
metastatic colorectal cancer: update on infusion-related reactions (IRRs).
Siena S, Glynne-Jones R, Thaler J, Adenis A, Preusser P, Aranda Aguilar E, Aapro MS, Loos A,
Esser R, Wilke H
ASCO 2007 Gastrointestinal Cancers Symposium, Orlando, USA January 2007
Abstract No: 353
Infusion-related reactions (IRR) associated with cetuximab plus irinotecan treatment in patients
with irinotecan-resistant metastatic colorectal cancer (mCRC): Findings from the MABEL study.
Siena S, Glynne-Jones R, Thaler J, Adenis A, Preusser P, Aguilar EA, Aapro MS, Loos AH,
Esser R, Wilke H
43rd ASCO Annual Meeting, Chicago, USA. June 2007
Abstract No: 4137