Department of Dermatology(D5a), Westmead Hospital, Westmead, Sydney, NSW, 2145, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Br J Dermatol. 2013 Dec;169(6):1310-3. doi: 10.1111/bjd.12519.
The treatment of metastatic melanoma has changed greatly with the development of inhibitors targeted at the mutated BRAF kinase present in up to 50% of metastatic melanoma cases. These agents, vemurafenib and dabrafenib, have been shown to increase median survival. Unfortunately, they have also been associated with the development of verrucal keratosis (VK) and cutaneous squamous cell carcinoma (cuSCC). These lesions require surgical excision, and when a large number of these lesions need to be treated, it can significantly affect the patient's quality of life.
To determine if acitretin is suitable as a chemopreventative agent against the development of verrucal keratosis and cuSCC, in patients on BRAF inhibitors.
Patients treated with a BRAF inhibitor, vemurafenib or dabrafenib, for stage IV metastatic melanoma, who had undergone more than five surgical excisions to remove lesions suggestive of cuSCC, were offered the opportunity to commence acitretin as a chemopreventative agent. Patients were evaluated every 4 weeks. Clinical and histological data were collected.
Eight patients, who had a total of 24 cuSCC removed, were included in the study. After commencement of acitretin, only five cuSCC were excised from two patients. The most significant reduction was in a patient who had developed 13 cuSCC over 10 months and only two cuSCC 3 months after commencing acitretin. No modifications in the dose of the BRAF inhibitor were made as a result of cuSCC in any of these patients.
Acitretin should be considered as a chemopreventative agent for VK and cuSCC in patients taking BRAF inhibitors, before considering dosage reductions.
随着针对多达 50%转移性黑色素瘤病例中突变 BRAF 激酶的靶向抑制剂的发展，转移性黑色素瘤的治疗发生了巨大变化。这些药物，vemurafenib 和 dabrafenib，已被证明能增加中位生存期。不幸的是，它们也与疣状角化病（VK）和皮肤鳞状细胞癌（cuSCC）的发展有关。这些病变需要手术切除，当需要治疗大量这些病变时，会显著影响患者的生活质量。
确定阿维 A 是否适合作为 BRAF 抑制剂治疗患者 VK 和 cuSCC 的化学预防剂。
接受 BRAF 抑制剂 vemurafenib 或 dabrafenib 治疗 IV 期转移性黑色素瘤的患者，已接受超过五次手术切除疑似 cuSCC 的病变，有机会开始使用阿维 A 作为化学预防剂。每 4 周评估一次患者。收集临床和组织学数据。
共有 8 名患者接受了研究，他们总共切除了 24 个 cuSCC。开始使用阿维 A 后，只有两名患者的 5 个 cuSCC 被切除。最显著的减少发生在一名患者身上，他在 10 个月内发展了 13 个 cuSCC，在开始使用阿维 A 3 个月后仅发展了 2 个 cuSCC。在这些患者中，由于 cuSCC，没有对 BRAF 抑制剂的剂量进行任何修改。
在考虑减少剂量之前，阿维 A 应被视为接受 BRAF 抑制剂治疗的患者 VK 和 cuSCC 的化学预防剂。
