Cetuximab

Monoclonal, chimeric IgG antibody that specifically blocks the epidermal growth factor receptor (EGFR) (see below growth factors) ( tyrosine kinase inhibitor), which is used for the therapy of colorectal cancer and squamous cell carcinoma of the head and neck.

• Specific and competitive binding to the EGF receptor (Epidermal Growth Factor Receptor). This prevents the coupling of endogenous ligands to the receptor. No dimerization of the receptor, consequently no activation of the tyrosine kinase by autophosphorylation. Therefore no initiation of the activating intracellular signalling cascade and no changes in the expression pattern of regulatory genes (cell growth and cell differentiation are inhibited).
• In vitro studies demonstrated an internalization of the receptor-antibody complex (i.e. return of the entire complex into the cell interior). The result is a reduction in the density of growth receptors on the cell surface. This reduces the invasion of tumour cells into healthy tissue and reduces metastasis.
• Influence on angiogenesis through reduced production of the angiogenesis factor VEGF. Result: Inhibition of proliferation and invasion of tumor cells.

From a dermatological point of view Acne medicamentosa (very common). The occurrence of skin changes should correlate with a therapy effect and is to be expected 2-6 weeks after the start of therapy.

Further dermatological side effects are extensive maculo-papular exanthema, urticaria up to anaphylactic shock.

There are also reports of erythema multiforme, diffuse alopecia, paronychia, vitiligo, puritus.

Acute hypersensitivity reactions were observed in some patients who received rituximab infusions for the first time. These immediate type reactions were attributed to a pre-existing "alpha-gal syndrome". Alpha-Gal syndrome represents a new class of food allergies. It is considered to be a summation anaphylaxis. The symptoms appear as a dose- and cofactor-dependent threshold phenomenon (cofactors can be exertion, non-steroidal anti-inflammatory drugs, alcohol, stress and infections). Allergic immediate reactions occur only with intravenous application of alpha-galactose-containing drugs (cetuximab, gelatin-containing colloid solutions e.g. Gelafundin®). As an alternative to cetuximab, panitumumab is listed as a humanized anti-EGFR-mAK without alpha-gal structures.

Test concentrations for allergy (recommended test concentrations cited in Sachs B et al. 2018)

• Prick: 5.0 mg/ml
• i.c. 0.5 mg/ml; 5.0 mg/ml.

1. Bauman JE et al (2007) Treatment of recurrent squamous cell carcinoma of the skin with cetuximab. Arch Dermatol 143: 889-892
2. Braun-Falco M et al (2006) Follicular drug reaction to cetuximab. dermatologist 57: 701-704
3. Busam KJ et al (2001) Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. Br J Dermatol 144: 1169-1176
4. Sachs B et al (2018) Acute hypersensitivity reactions to monoclonal antibodies for targeted therapy. dermatologist 69: 268-277