Al-Mansour Zeina, Pang Linda, Bathini Venu
Division of Hematology/Oncology, University of Massachusetts School of Medicine, Office #S5-726, 55 Lake Ave N, Worcester, MA, 01655, USA.
University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Drugs Aging. 2019 Jan;36(1):1-11. doi: 10.1007/s40266-018-0619-2.
With the worldwide trend of aging populations, the number of older adults who develop and survive cancer is likely to increase. In the last decade, oncology drug development has shifted away from conventional chemotherapeutics towards agents that can 'target' a driver mutation of a specific cancer or 'unleash' the patient's native immune system to attack the cancer-so-called molecularly targeted therapies and immunotherapeutics. The basic algorithms of cancer treatment in elderly patients are essentially the same as in younger patients; however, one needs to pay exceptional attention to the effects of co-morbidities, interaction with other drugs, and the organ function reserve of an older individual before determining his/her 'eligibility' for a specific cancer treatment modality. Despite the growing evidence of safety and effectiveness of combination chemotherapy in fit elderly patients, the data are still lacking concerning the use of currently approved targeted agents and immunotherapies. The current evidence, though limited, suggests reasonable tolerability with comparable efficacy in patients > 65 years old treated with immune-based therapies to that in younger controls; however, it is unclear if this leads to significant patient-relevant gains such as improved survival with an acceptable quality of life. Nonetheless, these newer agents remain better tolerated than cytotoxic chemotherapy in clinical practice, particularly in older patients. Alternatively, a personalized approach for elderly patients with consideration of the incidence and management of adverse effects, as well as strategies for optimizing efficacy in the context of an aging immune system, would be of utmost value in our aging cancer population. Future trials should also explore immune markers to predict response to these therapeutics in elderly patients, taking into consideration the effects of immunosenescence and immune modulation in aging hosts.
随着全球人口老龄化趋势，罹患癌症并存活下来的老年人数量可能会增加。在过去十年中，肿瘤药物研发已从传统化疗药物转向能够“靶向”特定癌症驱动突变或“激活”患者自身免疫系统来攻击癌症的药物，即所谓的分子靶向疗法和免疫疗法。老年患者癌症治疗的基本算法与年轻患者基本相同；然而，在确定老年个体是否适合特定癌症治疗方式之前，需要格外关注合并症的影响、与其他药物的相互作用以及其器官功能储备。尽管越来越多的证据表明联合化疗对身体状况良好的老年患者具有安全性和有效性，但关于目前已获批的靶向药物和免疫疗法的使用数据仍然缺乏。目前的证据虽然有限，但表明65岁以上接受免疫疗法治疗的患者与年轻对照组相比，耐受性合理且疗效相当；然而，尚不清楚这是否会带来与患者相关的显著益处，如在可接受的生活质量下提高生存率。尽管如此，在临床实践中，这些新型药物的耐受性仍然优于细胞毒性化疗，尤其是在老年患者中。此外，针对老年患者采取个性化方法，考虑不良反应的发生率和管理，以及在免疫系统老化背景下优化疗效的策略，对于我们不断老龄化的癌症患者群体将具有极大价值。未来的试验还应探索免疫标志物，以预测老年患者对这些疗法的反应，同时考虑免疫衰老和免疫调节在老年宿主中的影响。
