Dermatologic Toxicity Occurring During Anti-EGFR Monoclonal Inhibitor Therapy in Patients With Metastatic Colorectal Cancer: A Systematic Review

Abstract

Monoclonal antibody inhibitors of the epidermal growth factor receptor (EGFR) have been shown to improve outcomes for patients with metastatic colorectal cancer (mCRC) without RAS gene mutations. However, treatment with anti-EGFR agents can be associated with toxicities of the skin, nails, hair, and eyes. Because these dermatologic toxicities can result in treatment discontinuation and affect patient quality of life, their management is an important focus when administering anti-EGFR monoclonal antibodies. The present systematic review describes the current data reporting the nature and incidence of, and management and treatment options for, dermatologic toxicities occurring during anti-EGFR treatment of mCRC. A search of the National Library of Medicine PubMed database from January 1, 2009, to August 18, 2016, identified relevant reports discussing dermatologic toxicity management among patients with mCRC receiving anti-EGFR therapy. The studies were grouped by type and rated by level of evidence using the GRADE approach developed by the Agency for Healthcare Research and Quality. Overall, 269 reports were reviewed (nonrandomized trials, n = 120; randomized trials, n = 31; retrospective studies, n = 15; reviews, n = 39). Dermatologic toxicity of any grade occurs in most patients who receive anti-EGFR therapy; approximately 10% to 20% of patients experienced grade 3/4 toxicity. The most common dermatologic toxicities include papulopustular/acneiform rash, xerosis, and pruritus; however, nail changes, hair abnormalities, and ocular conditions also occur. Guidance for managing these toxicities includes the use of inexpensive emollient ointments and moisturizers, avoidance of sun exposure, avoidance of irritants, and the use of short showers. Several studies also found that preemptive treatment was more effective than reactive treatment at limiting the incidence and severity of skin toxicity. With appropriate treatment, the dermatologic toxicities associated with anti-EGFR monoclonal antibody therapy can be managed, minimizing patient discomfort and the need for therapy interruption and/or discontinuation. Additionally, preemptive treatment can reduce dermatologic toxicity severity, ultimately yielding better quality of life.

Update review of skin adverse events during treatment of lung cancer and colorectal carcinoma with epidermal growth receptor factor inhibitors

“…Rash is likely to occur, while pruritus and mucositis are less likely to be observed (21). Few patients had grade 3 skin-related toxicities (22). In phase I/II study of necitumumab, rash (70.5%), dry skin (18.2-67%), pruritus (11.4-60%), paronychia (36.4%) and grade ≥ 3 events, rash (20.5%) were observed (23,24).…”

Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC): A phase I dose escalating safety study and randomised dose expansion of AZD8931 in combination with oxaliplatin and capecitabine chemotherapy in patients with oesophagogastric adenocarcinoma

“…DEBIOC is also the first study to consider AZD8931 in long-term postsurgical maintenance therapy, during which time 58% patients experienced AZD8931-related AEs, the most common being skin rash. Although skin rash is a common grade IIIeIV toxicity typically occurring in 10e20% of patients receiving tyrosine kinase inhibitors [29], no events of this nature grade III were observed with AZD8931 in the expansion phase. The discordance between the diagnostic biopsy and resection specimens for both HER2 and EGFR status, demonstrates potential heterogeneity of expression in these cancers or indeed a neoadjuvant treatment effect.…”

Patient voice on management of facial dermatological adverse events with targeted therapies: a qualitative study

“…A previous study with patients undergoing oral chemotherapy reported that many patients feel helpless at home when they do not have enough information and knowledge about their treatment and symptoms [7]. In general, education on the self-management of dAEs is recommended both before and after initiation of cancer therapy [4, 5, 17, 18]. However, it is difficult for patients to predict the disease outlook because various types of dAEs may develop [1, 18], and exacerbation and improvement of symptoms often repeatedly occur after the initiation of EGFR inhibitors.…”

“…Proper management is essential to minimize patient discomfort during cancer therapy [4, 5]. Although there are no standard therapies for targeted therapy-induced dAEs, treatments, such as skin moisturizers and topical ointments, have been recommended to prevent and reduce the symptoms [6].…”