Reacções cutâneas adversas aos inibidores do receptor do factor de crescimento epidérmico: estudo de 14 doentes

Abstract

BACKGROUND: Cetuximab and erlotinib, epidermal growth factor receptor inhibitors, often cause peculiar adverse cutaneous reactions. OBJECTIVES: Our aim was to evaluate adverse cutaneous reactions and their management in patients undergoing treatment with cetuximab and erlotinib. PATIENTS AND METHODS: Between March/2005 and September/2009, we observed 14 patients with a mean age of 59.6 years undergoing treatment with cetuximab (7) or erlotinib (7), due to lung(10) or colorectal cancer (4). We evaluated the interval between introduction of the drug and onset of symptoms, treatment response, and the clinical pattern of evolution of the cutaneous reaction retrospectively. RESULTS: Twelve patients presented papular-pustular eruption typically affecting the face, chest and back, which appeared in average 13.5 days after starting the drug treatment. The patients underwent oral treatment with minocycline or doxycycline and topical treatment with metronidazole, benzoyl peroxide and/or corticosteroids. All patients showed improvement of the lesions. Five patients presented periungual pyogenic granulomas, which were associated with paronychia in 4 cases, after an average of 8 weeks of treatment. There was improvement of the lesions with topical treatment (antibiotics, corticosteroids and antiseptics). Xerosis was observed in some patients. Other less frequent adverse side effects such as telangiectasia and angiomas, hair and eyelash alterations, and eruptive melanocytic nevi were also described. Treatment with epidermal growth factor receptor inhibitor was maintained in most patients. CONCLUSION: The increasing use of these targeted therapies requires knowledge of their adverse cutaneous side effects to ensure timely intervention in order to allow the continuation of the therapy. Keywords: Drug eruptions; Drug toxicity; Epidermal growth factor; Receptor, epidermal growth factor Resumo: FUNDAMENTOS: O cetuximab e o erlotinib, inibidores do receptor do factor de crescimento epidérmico, provocam frequentemente reacções cutâneas adversas peculiares. OBJETIVOS: Caracterizar do ponto de vista clínico-evolutivo as reacções cutâneas adversas e avaliar a sua abordagem terapêutica. METODOLOGIA: Entre março/2005 e setembro/2009 foram seguidos 14 doentes com idade média de 59,6 anos, em tratamento com cetuximab (7) ou erlotinib (7), por neoplasia pulmonar (10) ou colorrectal (4). Retrospectivamente foi avaliado o padrão clíni-co evolutivo de reacção cutânea, o intervalo entre a introdução do fármaco e o início dos sintomas e a resposta ao tratamento. RESULTADOS: Doze doentes apresentaram erupção papulopustulosa predominantemente na face, decote e dorso, em média 13,5 dias após o início do fármaco. Efectuaram tratamento oral com minociclina ou doxiciclina e tópico com metronidazol, peróxi-do de benzoílo e/ou corticoide. Ocorreu melhoria das lesões em todos os doentes. Cinco doentes, em média oito semanas após o início da terapia, apresentaram granulomas piogénicos periungueais, em quatro casos associados a paroníquia, melhor...

Cutaneous Side Effects and Transepidermal Water Loss To Gefitinib: A Study of 11 Patients

“…Similar results have been published in other studies of gefitinib treatment. Hair disorder has once been reported, by Santiago et al [5], with one of seven patients who used erlotinib EGFR inhibitor experiencing hair growth and texture alteration. The hair became thin, brittle or curled.…”

“…One type, non-small cell lung carcinoma (NSCLC), accounts for 85% of all lung cancers [4]. Prior studies have demonstrated the important role of epidermal growth factor receptor (EGFR), a tyrosine kinase growth factor family transmembrane glycoprotein [5–7], in which gene mutation happens in 40–80% of all NSCLC patients [1, 4, 8]. …”

“…Cutaneous toxicities are the most common forms of EGFR inhibitor side effects [13], affecting approximately 45–100% of patients [13, 14] and varying from papulopustular rashes on the face and upper side trunk to xerosis cutis, paronychia, hair disorder, and pruritus [14, 15], leading to treatment modification or interruption in 8–17% of patients [14]. These side effects are related to the EGFR expression role in promoting the proliferation, survival, motility, and regulation of the differentiation and keratinization [16] of human skin cells [17], such as keratinocytes [18], corneocytes, sweat glands and hair follicles [5]. …”

Use of amniotic membrane graft in the surgical management of cicatricial ectropion associated with cetuximab therapy

“…Cetuximab is an EGFR inhibitor indicated for the treatment of metastatic or unresectable colorectal cancer and squamous cell tumors of the head and neck [ 1 ]. EGFR is expressed in normal epidermis, sweat glands and hair follicles, and its inhibition by cetuximab has been associated with numerous cutaneous side effects [ 2 ]. In a series of 14 patients by Santiago et al [ 2 ], adverse cutaneous reactions following cetuximab therapy included acneiform skin rash, paronychia, xerosis, and change in hair texture and growth.…”

“…Periocular side effects, such as blepharitis, trichomegaly, dry eye and conjunctivitis, have also been reported, though less frequently [ 2 – 7 ]. Among these, trichomegaly is the most common, and can be complicated by trichiasis and corneal erosion [ 8 ].…”