Audigier-Valette Clarisse, Girard Nicolas, Cortot Alexis B, Mennecier Bertrand, Debieuvre Didier, Planchard David, Zalcman Gérard, Moro-Sibilot Denis, Cadranel Jacques, Barlesi Fabrice
CHITS Toulon, Hôpital de Toulon, Service de pneumologie, 54, rue Sainte-Claire-Deville, 83056 Toulon, France.
Université Claude-Bernard Lyon 1, Hospices civils de Lyon, Hôpital Louis-Pradel, Service de pneumologie, 69677 Lyon, France.
Bull Cancer. 2014 Sep;101(9):823-31. doi: 10.1684/bdc.2014.1976.
Crizotinib (XALKORI(™), Pfizer) is a tyrosine kinase inhibitor of ALK, MET, and ROS1, which is currently approved for the second line treatment for ALK-rearranged lung cancer. This work from an expert group, based on the review of the data from the Profile studies, aims to provide practical elements in order to optimize the tolerability of crizotinib. Specific major or frequent side effects of crizotinib are discussed: visual disturbances, cardiac effects, elevated transaminases, and hypogonadism. In the routine practice, patients should be advised about visual disturbances, especially with regard to driving in low brightness. Digestive disorders related to crizotinib are exceptionally persistent or severe. Dietary measures and symptomatic treatments usually control these disorders. It is recommended to perform an electrocardiogram before introduction of crizotinib, to identify prolonged QT interval. Torsades de pointes may produce dizziness or syncope. Hypogonadism should be considered in case of fatigue, decreased libido, and even depression, taking into account that these symptoms may be related to cancer; testosterone serum level should be measured to identify patients that may be eligible to receive a supplementation. Monitoring of liver function tests, including transaminases and bilirubin, is necessary. To conclude, these practical elements are helpful to optimize treatment with crizotinib in patients with ALK-rearranged lung cancer; in the future, academic initiatives should be taken to study these aspects, based on the monitoring of large cohorts of patients treated with crizotinib.
克唑替尼（XALKORI(™)，辉瑞公司）是一种ALK、MET和ROS1的酪氨酸激酶抑制剂，目前被批准用于ALK重排肺癌的二线治疗。该专家小组的这项工作基于对Profile研究数据的回顾，旨在提供实用要点以优化克唑替尼的耐受性。文中讨论了克唑替尼特定的主要或常见副作用：视觉障碍、心脏影响、转氨酶升高和性腺功能减退。在常规实践中，应告知患者有关视觉障碍的情况，尤其是在低亮度环境下驾驶时。与克唑替尼相关的消化系统紊乱异常持久或严重。饮食措施和对症治疗通常可控制这些紊乱。建议在开始使用克唑替尼之前进行心电图检查，以识别QT间期延长。尖端扭转型室速可能会导致头晕或晕厥。出现疲劳、性欲减退甚至抑郁时应考虑性腺功能减退，同时要考虑到这些症状可能与癌症有关；应测量血清睾酮水平以确定可能有资格接受补充治疗的患者。有必要监测肝功能检查，包括转氨酶和胆红素。总之，这些实用要点有助于优化ALK重排肺癌患者使用克唑替尼的治疗；未来，应基于对大量接受克唑替尼治疗患者的监测开展学术研究来探讨这些方面。
