Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225

Background C225 is an antibody to the epidermal growth factor receptor (EGF R), and inhibits growth of various tumour cells. The antibody is currently being used as a therapeutic agent in several clinical trials of patients wi th carcinomas. Objectives To determine and investigate the cutaneous side-effects in cance r patients treated with C225. Methods We clinically examined 10 patients treated with C225, and performed immunohistochemical and in situ hybridization studies on skin biopsies. Results The most common cutaneous reaction to C225 therapy was the developm ent of an acneiform follicular eruption, which was most pronounced on the f ace, chest and upper back and typically manifested a week after the onset o f treatment. The consistency of the morphology and timing of the clinical f indings in 10 different patients following monotherapy with C225 strongly s uggested a direct biological effect of the antibody. Additional dermatologi cal side-effects included focal areas of tender paronychial inflammation of toes and fingers and small aphthous ulcers of the oral mucosa. Serial punc h biopsies of chest skin before and after treatment (at 8 days) revealed tw o main reaction patterns: a superficial dermal inflammatory cell infiltrate surrounding hyperkeratotic and ectatic follicular infundibula, and a suppu rative superficial folliculitis. In two biopsies focal intraepidermal acant holysis was found. Microbiological cultures failed to reveal an infectious aetiology. Immunohistochemical and in situ hybridization studies on a subse t of the biopsies showed an increase in the expression of p27(Kip1) in epid ermal keratinocytes after treatment with C225. Conclusions Our findings support the concept that p27(Kip1) plays a part in the in vivo regulation of follicular and epidermal homeostasis by EGFR.