Baas, J.M., Krens, L.L., Guchelaar, H.-J., Ouwerkerk, J., de Jong, F.A., Lavrijsen, A.P., & Gelderblom, H. (2012). Recommendations on management of EGFR inhibitor-induced skin toxicity: A systematic review. Cancer Treatment Reviews, 38, 505–514.

To evaluate evidence regarding the prevention and management of epidermal growth factor receptor–inhibitor (EGFRI)-related skin toxicities. Secondary objectives were to review current knowledge on (a) the pathophysiology of this type of skin toxicity, (b) prediction of the occurrence of (severe) skin toxicity in individual patients, (c) the need for adequate management of skin toxicities, and (d) the possibility of any interference between management of skin toxicities and the antitumor effect of EGFRIs.

The database searched was MEDLINE.

Search keywords were skin toxicity, rash, acneiform rash, acne, exanthema, cetuximab, panitumumab, erlotinib, gefitinib, lapatinib, monoclonal antibodies, EGFR, antibiotics, antibody dependent cell mediated cytotoxicity, ​and NK cells.

Studies were included in the review if they reported on the testing any type of management (prophylactic as well as reactive) using topical agents, systemic agents, or both.

Exclusion criteria were not specified.

A total of 283 references were retrieved. No quality rating or method of study evaluation was described.

• Eighty final studies were included, with five randomized controlled trials comprising 338 patients.
• The samples across studies ranged from 16 to 110 patients.

Patients were undergoing the active antitumor treatment phase of care.

• Reviews with findings regarding the pathophysiology of skin toxicities, factors that predict skin toxicity, and potential interactions between the management of skin toxicities and antitumor effects of EGFRIs concluded that skin toxicities should be prevented or managed because of their impact on quality of life.
• The studies also provided a review of clinical trials for the prevention and management of skin toxicities. They noted the lack of a strong evidence base, and that tetracycline derivatives have the strongest evidence, despite review findings of conflicting results in this area.

A strong evidence base is lacking for any recommendations on the prevention and management of skin toxicities with EGFRIs.

• How evidence was evaluated or graded is unclear.
• Recommendations were made for tetracyclines, despite the review of evidence showing conflicting results.
• The search was limited, with only one database used.

This review adds to the current observation that a lack of strong evidence exists for any specific set of interventions to prevent or manage skin toxicities in patients receiving EGFRIs. However, the review suggests that the prior belief in letting skin effects go uncontrolled, as they were seen as an indicator of an antitumor treatment effect, is not appropriate.