Abstract：
BRAF mutations occur commonly in metastatic melanomas and inhibition of mutant BRAF and the downstream kinase MEK results in rapid tumor regression and prolonged survival in patients. Combined therapy with BRAF and MEK inhibition improves response rate, progression free survival and overall survival compared with single agent BRAF inhibition, and reduces the skin toxicity that is seen with BRAF inhibitor monotherapy. However, this combination is associated with an increase in other toxicities, particularly drug-related pyrexia, which affects approximately 50% of patients treated with dabrafenib and trametinib (CombiDT). We provide guidance on managing adverse events likely to arise during treatment with combination BRAF and MEK inhibition with CombiDT: pyrexia, skin conditions, fatigue; and discuss management of CombiDT during surgery and radiotherapy. By improving tolerability and in particular preventing unnecessary treatment cessations or reduction in drug exposure, best outcomes can be achieved for patients undergoing CombiDT therapy.
摘要：
BRAF突变通常发生在转移性黑色素瘤中，抑制突变型BRAF和下游激酶MEK可导致肿瘤快速消退并延长患者生存期。BRAF和MEK抑制联合治疗可改善反应率，无进展生存期和总生存期与单药BRAF抑制相比，并降低BRAF抑制剂单药治疗的皮肤毒性。然而,这种组合与其他毒性的增加有关，特别是与药物有关的发热，这影响了大约50%接受达拉非尼和曲美替尼（CombiDT）治疗的患者。我们提供有关管理在使用CombiDT联合BRAF和MEK抑制治疗期间可能出现的不良事件的指导：发热，皮肤状况,疲劳；并讨论手术和放疗期间CombiDT的管理。通过提高耐受性，特别是防止不必要的治疗终止或减少药物暴露，接受CombiDT治疗的患者可以取得最佳结果.
