Epidermal growth factor receptor inhibitor-associated rash prevented by oral tetracyclines

What is it about?

Small molecules and monoclonal antibodies that inhibit the epidermal growth factor receptor (EGFR) are frequently used in the treatment of metastatic non-small-cell lung cancer, col- orectal cancer and head and neck cancer. However, EGFR inhi- bitors, including erlotinib, gefitinib, lapatinib, cetuximab and panitumumab, elicit cutaneous adverse events in more than 70% of patients. Within weeks following start of treatment patients develop an eruption consisting of follicular papules and pustules predominantly affecting skin areas rich in seba- ceous glands. In addition, patients may develop xerosis, pruri- tus, fissures, paronychia and hair growth abnormalities. Although the skin eruption has a tendency to improve spontaneously in months, the papulopustular rash can be debilitating and a reason for concern and discomfort in patients. In a minority they can be severe and necessitate dose reduction or discontinuation of EGFR inhibitor treatment. Depending on the severity of cutaneous adverse events, vari- ous local and systemic drugs are used, such as skin moisturizers, sunscreens, antibiotic gels, corticosteroid creams, vitamin K cream, oral tetracyclines, isotretinoin and prednisone. In this issue of the British Journal of Dermatology, Petrelli and col- leagues present the results of a systematic review and meta-ana- lysis of the efficacy of doxycycline, minocycline and tetracycline in the prevention of EGFR inhibitor-induced skin rash. Of 827 articles on prophylactic treatment with tetracyclines, nine ran- domized and four retrospective studies met their inclusion crite- ria. The individual studies included 26–150 patients and mostly pointed to efficacy of prophylactic treatment. This meta-analysis on over 1000 patients clearly showed that the incidence and severity of the EGFR inhibitor-induced papulopustular rash was reduced by prophylactic treatment with doxycycline or minocy- cline. The likelihood of developing this rash was reduced by 50% by prophylactic treatment; severe rash (grade III–IV) was 70% less likely to develop. Although tetracyclines reduced the severity of the follicular papulopustular eruption and of parony- chia, they did not appear to prevent xerosis and skin fissures. Interestingly, treatment effects on all grades of rash were statis- tically significant only for studies conducted with minocycline, but not for doxycycline. Contrary to the findings in this review, a recent study included in the meta-analysis concluded that pro- phylactic treatment with doxycycline reduces the severity of reduces the severity of skin lesions, but not the incidence

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