Wadia Roxanne J, Stolar Marilyn, Grens Clarice, Ehrlich Barbara E, Chao Herta H
Department of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA.
Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut, USA.
Oncotarget. 2017 Dec 19;9(7):7322-7331. doi: 10.18632/oncotarget.23467. eCollection 2018 Jan 26.
Peripheral neuropathy is a major adverse effect in the use of chemotherapeutic drugs. In nearly 50% of patients, chemotherapy induced peripheral neuropathy (CIPN) has been reported as irreversible. With increasing numbers of patients surviving treatment as well as increasing duration of survival after treatment, reducing the side effects of chemotherapy and improving the quality of life has become a major focus of cancer survivorship. Multiple classes of chemotherapeutic drugs including taxanes, platinum agents and vinka alkaloids list peripheral neuropathy as the main dose-limiting side effect of treatment. We previously found that drugs that interfere with the microtubule function, including taxanes and vinca alkaloids, bind to neuronal calcium sensor 1 (NCS1), leading to aberrant calcium signaling. The altered calcium signaling can be mitigated by application of drugs used to treat bipolar disease (e.g., lithium and valproic acid) prior to initiation of chemotherapy. Because pre-treatment with these drugs prevented CIPN in mice treated with taxanes, we sought clinical evidence by performing a retrospective chart review study of the VA electronic health record to see whether or not there would be evidence to support our scientific belief that patients treated with lithium or valproic acid while receiving chemotherapy have a lower risk for development of CIPN than patients who received chemotherapy alone. Our data did provide evidence supporting the belief that treatment with lithium or valproic acid concurrently with chemotherapy was associated with a decreased incidence of developing CIPN.
周围神经病变是化疗药物使用中的一种主要不良反应。据报道，在近50%的患者中，化疗引起的周围神经病变（CIPN）是不可逆的。随着治疗后存活患者数量的增加以及治疗后生存期的延长，减少化疗副作用和提高生活质量已成为癌症幸存者的主要关注点。包括紫杉烷类、铂类药物和长春花生物碱在内的多类化疗药物都将周围神经病变列为治疗的主要剂量限制性副作用。我们之前发现，干扰微管功能的药物，包括紫杉烷类和长春花生物碱，会与神经元钙传感器1（NCS1）结合，导致异常的钙信号传导。在开始化疗之前应用用于治疗双相情感障碍的药物（如锂盐和丙戊酸）可以减轻改变的钙信号传导。由于用这些药物进行预处理可预防用紫杉烷类治疗的小鼠发生CIPN，我们通过对退伍军人事务部电子健康记录进行回顾性图表审查研究来寻找临床证据，以查看是否有证据支持我们的科学观点，即接受化疗时使用锂盐或丙戊酸治疗的患者发生CIPN的风险低于仅接受化疗的患者。我们的数据确实提供了证据支持这样的观点，即化疗时同时使用锂盐或丙戊酸治疗与CIPN发生率降低有关。
