Department of Dermatology, Chelsea and Westminster Hospital, London SW10 9NH, U.K.
Br J Dermatol. 2012 Nov;167(5):987-94. doi: 10.1111/bjd.12010.
Until recently, no effective treatment was available for patients with metastatic malignant melanoma, and median overall survival was little more than 6 months with the current standard of care, dacarbazine. In 2012, the first specific BRAF mutation inhibitor, vemurafenib, was licensed for the monotherapy of adults with BRAF V600 mutation-positive unresectable or metastatic melanoma. Like other targeted therapies, vemurafenib is associated with a predictable pattern of adverse events, including skin toxicities. We review the most common cutaneous adverse events associated with vemurafenib, based on data from clinical trials, and our own experiences of treating patients in trials and clinical practice. Overall, these toxicities are not preventable, but they rarely necessitate permanent treatment discontinuation and are generally manageable with dose modification and supportive care. We provide a treatment algorithm offering guidance on the most appropriate approach to managing the main skin toxicities to help clinicians unfamiliar with this novel agent to become confident in using vemurafenib effectively in the management of patients with metastatic melanoma.
直到最近,转移性恶性黑色素瘤患者还没有有效的治疗方法,目前的标准治疗药物达卡巴嗪的中位总生存期略多于 6 个月。2012 年,第一个针对 BRAF 突变的抑制剂维莫非尼获得批准,用于治疗 BRAF V600 突变阳性、不可切除或转移性黑色素瘤的成人单药治疗。与其他靶向治疗药物一样,维莫非尼与可预测的不良事件相关,包括皮肤毒性。我们根据临床试验数据和我们在临床试验和临床实践中治疗患者的经验,回顾了与维莫非尼相关的最常见皮肤不良事件。总的来说,这些毒性是不可预防的,但它们很少需要永久停止治疗,并且通常可以通过剂量调整和支持性护理来控制。我们提供了一个治疗算法,为管理主要皮肤毒性提供了指导,以帮助不熟悉这种新型药物的临床医生有信心在转移性黑色素瘤患者的治疗中有效使用维莫非尼。