INTRODUCTIONFolliculitis is the most common side effect of epidermal growth factor receptor (EGFR) inhibitors (EGFRIs). It is often apparent, altering patients' quality of life and possibly impacting compliance. Variations in terms of the treatment-related incidence and intensity have not been fully elucidated. Tetracyclines have been recommended for the prophylaxis and treatment of folliculitis but their efficacy is yet to be established.MATERIALS AND METHODSWe carried out two systematic literature reviews. The first assessed the preventive and curative efficacy of tetracyclines. The second assessed the incidence of grade 3-4 folliculitis in the main clinical studies published.RESULTSIn four randomized studies, preventive tetracycline treatment was associated with a significantly lower incidence of grade 2-3 folliculitis and a better quality of life in three of the four studies. In curative terms, tetracycline efficacy was not evaluated in any randomized study, but an improvement in grade ≥2 folliculitis was reported in case series. The frequency and severity of folliculitis seem to be greater with the antibodies than with the tyrosine kinase inhibitors. Analysis restricted to lung cancer studies showed a statistically greater incidence in terms of grade 3-4 folliculitis with cetuximab (9%) and erlotinib (8%) than with gefitinib (2%) (p < .0001).CONCLUSIONUnless contraindicated, a tetracycline should be routinely prescribed prophylactically for patients treated with an EGFRI (level of evidence, B2). In curative therapy, the level of evidence for tetracycline efficacy is low (level of evidence, D). The incidence of grade 3-4 folliculitis induced by EGFRIs appears to be lower with gefitinib.