Vemurafenib-related cutaneous side effects ameliorated by acitretin

Background: Vemurafenib is a BRAF kinase inhibitor that improves the survival of patients with metastatic melanoma, who have the V600E BRAF mutation. The development of cutaneous neoplasms, including squamous cell carcinomas (SCCs), keratoacanthomas (KAs), and hyperkeratotic papules is one of the most common adverse effects of this therapy. Systemic retinoids, such as isotretinoin and acitretin, have been used for chemoprophylaxis in individuals at high risk of developing many non-melanoma skin cancers, such as immunosuppressed solid organ transplant recipients. These agents may reduce and delay the growth of skin cancers by exerting their effects during the promotion and progression stages of carcinogenesis. Observations: We report a series of two patients with stage IV metastatic melanoma who presented to our Dermatology clinic for evaluation of a florid eruption of hyperkeratotic neoplasms (verrucae, actinic keratoses, and SCCs) within one month of initiating vemurafenib. After one month of acitretin, substantially fewer new neoplasms were observed in both patients. Conclusions: Although not definitive, these cases suggest that acitretin may have a role in chemoprevention of a subset of patients with rapidly developing vemurafenib-associated neoplasms and slowing the progression of more aggressive SCCs and KAs. Future studies to evaluate acitretin may substantially improve the morbidity associated with vemurafenib.