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Background: Anti-EGFR therapies, like cetuximab or panitumumab, are amongst the most extensively used therapies for metastatic colorectal cancer (mCRC), but both are associated with the development of skin toxicities. Nevertheless, when doxycycline 100 mg/12h, is administered during the 6 weeks, the incidence of specific grade 2 skin toxicities is reduced in more than 50%. The study objective is to assess safety and efficacy of reduced dose of doxycycline in the prevention of skin toxicities in patients with metastatic colorectal cancer (mCRC) treated with FOLFOX or FOLFIRI + anti-EGFR.Methods: This was a Phase II, single-arm, multicentre clinical trial. Eligible patients were 18 years, ECOG 2, had adequate organ functions, with wild-type RAS mCRC, adequate liver, kidney and bone marrow function, and a treatment plan based on FOLFOX or FOLFIRI + anti-EGFR as first-line treatment. In the first stage, 10 patients received doxycycline 50 mg/day for 6 weeks beginning one day before the administration of the first anti-EGFR dose. If > 3 patients presented grade 2 skin toxicities, the doxycycline dose was increased to 100 mg/day for the next 30 patients. Patients received moisturizer and sunscreen during treatment. Skin toxicity severity was graded according to NCI CTCAE v4.03. It was assumed that if a 50% reduction in the incidence of grade 2 skin toxicities would be achieved, resulting in an estimated incidence of 30%, the prophylaxis was effective. abstracts Annals of Oncology Volume 32 -Issue S3 -2021 S117