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转移性黑色素瘤的新型疗法:老年患者使用情况的最新进展

Novel Therapies for Metastatic Melanoma: An Update on Their Use in Older Patients.

作者信息

Rogiers Aljosja, van den Oord Joost J, Garmyn Marjan, Stas Marguerite, Kenis Cindy, Wildiers Hans, Marine Jean-Christophe, Wolter Pascal

机构信息

Department of General Medical Oncology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.

Laboratory for Molecular Cancer Biology, Center for the Biology of Disease, VIB, Leuven, Belgium.

出版信息

Drugs Aging. 2015 Oct;32(10):821-34. doi: 10.1007/s40266-015-0304-7.

Abstract

Cutaneous melanoma is the most aggressive form of skin cancer. With age as a risk factor, melanoma is projected to become a substantial healthcare burden. The clinical course of melanoma in older patients is different from that in middle-aged and younger patients: melanomas are thicker, have higher mitotic rates and are more likely to be ulcerated. Older patients also have a higher mortality rate, yet, paradoxically, have a lower rate of lymph node metastases. After decades of no significant progress in the treatment of this devastating disease, novel insights into the mechanisms underlying the pathophysiology of metastatic melanoma have led to new and remarkably efficient therapeutic opportunities. The discovery that about half of all melanomas carry BRAF mutations led to the introduction of targeted therapy with significant improvements in clinical outcomes. Although these drugs appear to be equally effective in older patients, specific considerations regarding adverse events are required. Besides targeted therapy, immunotherapy has emerged as an alternative therapeutic option. Antibodies that block cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) can induce responses with high durability. Despite an aging immune system, older patients seem to benefit to the same degree from these treatments, apparently without increased toxicity. In this review, we focus on the epidemiology, clinicopathological features, and recent developments of systemic treatment in cutaneous melanoma with regard to older patients.

摘要

皮肤黑色素瘤是最具侵袭性的皮肤癌形式。随着年龄成为一个风险因素,黑色素瘤预计将成为一项重大的医疗负担。老年患者黑色素瘤的临床病程与中年及年轻患者不同:黑色素瘤更厚,有更高的有丝分裂率,且更易发生溃疡。老年患者的死亡率也更高,但矛盾的是,其淋巴结转移率较低。在对这种毁灭性疾病的治疗几十年没有取得显著进展之后,对转移性黑色素瘤病理生理学潜在机制的新见解带来了新的且非常有效的治疗机会。发现约一半的黑色素瘤携带BRAF突变导致了靶向治疗的引入,临床结果有显著改善。尽管这些药物在老年患者中似乎同样有效,但需要对不良事件进行特殊考虑。除了靶向治疗,免疫疗法已成为另一种治疗选择。阻断细胞毒性T淋巴细胞抗原4(CTLA-4)和程序性细胞死亡蛋白1(PD-1)的抗体可诱导具有高持久性的反应。尽管免疫系统老化,但老年患者似乎从这些治疗中受益程度相同,显然没有增加毒性。在本综述中,我们关注老年患者皮肤黑色素瘤的流行病学、临床病理特征以及全身治疗的最新进展。

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