Uribe Pablo, Anforth Rachael M, Kefford Richard F, Fernandez-Peñas Pablo
Departments of aDermatology bMedical Oncology, Westmead Hospital cSydney Medical School, The University of Sydney dMelanoma Institute Australia, Sydney, New South Wales, Australia eDepartment of Dermatology, School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.
Melanoma Res. 2014 Oct;24(5):501-3. doi: 10.1097/CMR.0000000000000096.
BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) increase survival in BRAF mutant metastatic melanoma patients; however, they induce a well-known spectrum of cutaneous side effects during treatment. Whereas the BRAFi dabrafenib induces cutaneous squamous cell carcinomas and verrucal keratosis, the MEKi trametinib frequently induces acneiform eruptions that are reversible after drug discontinuation. Furthermore, when dabrafenib and trametinib are used in combination, there are fewer cutaneous toxicities. We report a patient with BRAF mutant metastatic melanoma treated with the BRAFi/MEKi combination therapy who developed an acneiform eruption after treatment discontinuation rather than during active therapy. Moreover, the eruption resolved when the combination treatment was reintroduced and recurred after increasing the dose of trametinib. The eruption may be explained by the longer half-life of trametinib (4.5 days) compared with dabrafenib (5.2 h). This is the first case reported with this particular side effect induced after stopping the treatment and could become more frequent as the BRAFi/MEKi combination of drugs is more frequently prescribed.
BRAF抑制剂（BRAFi）和MEK抑制剂（MEKi）可提高BRAF突变转移性黑色素瘤患者的生存率；然而，它们在治疗期间会引发一系列众所周知的皮肤副作用。BRAFi达拉非尼会诱发皮肤鳞状细胞癌和疣状角化病，而MEKi曲美替尼则经常诱发痤疮样皮疹，停药后皮疹可逆转。此外，当达拉非尼和曲美替尼联合使用时，皮肤毒性会减少。我们报告了一名接受BRAFi/MEKi联合治疗的BRAF突变转移性黑色素瘤患者，该患者在停药后而非积极治疗期间出现了痤疮样皮疹。此外，重新引入联合治疗时皮疹消退，增加曲美替尼剂量后皮疹复发。与达拉非尼（5.2小时）相比，曲美替尼的半衰期更长（4.5天），这可能解释了皮疹的发生。这是首例报告的停药后诱发这种特殊副作用的病例，随着BRAFi/MEKi联合用药的处方越来越频繁，这种情况可能会更加常见。
