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等 。本研究纳入的患者既往有饮酒史,用药前三酰甘油 酶基因阳性晚期肺腺癌的临床观察[J].中国药房,2019,
[23]
水平为420 mg/dL,6个月后三酰甘油水平>5 680 mg/dL 30(2):240-243.
并诱发胰腺炎。该患者在治疗期间仅使用阿来替尼1种 [ 5 ] GADGEEL S M,SHAW A T,GOVINDAN R,et al. Pooled
药物,故考虑 ADR 由阿来替尼导致,经停药、血浆置换 analysis of CNS response to alectinib in two studies of
pretreated patients with ALK-positive non-small-cell lung
等处理后症状好转。这提示患者使用阿来替尼后,临床
cancer[J]. J Clin Oncol,2016,34(34):4079-4085.
药师应提醒其禁酒并常规监测三酰甘油、淀粉酶和脂肪
[ 6 ] LIN J J,ZHU V W,YODA S,et al. Impact of EML4-ALK
酶水平,并密切关注三酰甘油水平升高的患者。本研究
variant on resistance mechanisms and clinical outcomes in
纳入的17例患者中有1例用药1个月后出现左上腹部疼
ALK-positive lung cancer[J]. J Clin Oncol,2018,36(12):
痛、呼吸急促,腹部 CT 示十二指肠溃疡穿孔,排除其他 1199-1206.
致胃肠穿孔的因素后,考虑该ADR与阿来替尼有关,也 [ 7 ] PELLEGRINO B,FACCHINETTI F,BORDI P,et al.
是新发ADR。但目前关于阿来替尼致胃肠道穿孔ADR Lung toxicity in non-small-cell lung cancer patients ex-
的机制尚不明确,还需临床进一步探讨。该 ADR 尽管 posed to ALK inhibitors:report of a peculiar case and sys-
罕见但应引起临床重视。 tematic review of the literature[J]. Clin Lung Cancer,
3.8 血液系统ADR 2018,19:e151-e161.
本研究纳入患者中有 1 例为阿来替尼致溶血性贫 [ 8 ] COSTA R B,COSTA R L B,TALAMANTES S M,et al.
血,目前认为药源性溶血性贫血发生机制主要有 4 种: Systematic review and meta-analysis of selected toxicities
(1)半抗原型;(2)免疫复合物型;(3)自身抗体型;(4)非 of approved ALK inhibitors in metastatic non-small cell
lung cancer[J]. Oncotarget,2018,9(31):22137-22146.
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免疫性蛋白吸附型 。该患者一线给予培美曲塞治疗,
[ 9 ] KOIZUMI T,FUKUSHIMA T,GOMI D,et al. Alectinib-
有研究表明,培美曲塞可促进淋巴细胞活化,诱导自身
induced alopecia in a patient with anaplastic lymphoma
抗体的产生 ,加用阿来替尼等靶向药物时会抑制自身
[39]
kinase-positive non-small cell lung cancer[J]. Case Rep
抗体的产生从而引起贫血性溶血的发生。虽然这种
Oncol,2016,9(1):212-215.
ADR发生率不高,但仍需临床加强关注。 [10] ANDERSON B E,LUCZAK T S,RIES L M,et al. Suc-
3.9 ADR关联性 cessful alectinib desensitization in a patient with anaplas-
笔者对 17 例患者进行 ADR 关联性再评价结果显 tic lymphoma kinase-positive adenocarcinoma of the lung
示,有 2 例患者 [13,24] 的 ADR 关联性评价结果与文献报道 and alectinib-induced drug rash[J]. J Oncol Pharm Pract,
不一致,其原因可能为诺氏评估量表(纳入文献均采用 2020,26(8):2028-2030.
诺氏评估量表进行关联性评价)与我国 ADR 相关性评 [11] FAROOQ S,NARALA S,PACHA O. Alectinib-associa-
价标准有所差异。 ted drug reaction with eosinophilia and systemic symp-
综上所述,阿来替尼作为第二代ALK 抑制剂,虽然 toms syndrome[J]. JAAD Case Rep,2020,6(12):1339-
疗效确切,但其ADR也不容忽视。本研究分析表明,女 1341.
[12] KIMURA T,SOWA-OSAKO J,NAKAI T,et al. Alec-
性患者及 50 岁以上患者使用阿来替尼更易发生 ADR,
tinib-induced erythema multiforme and successful rechal-
且发生时间多在用药后30 d内。其ADR累及多个器官/
lenge with alectinib in a patient with anaplastic lymphoma
系统,以皮肤及其附件系统和呼吸系统为主,应特别关
kinase-rearranged lung cancer[J]. Case Rep Oncol,2016,9
注脱发、胰腺炎和十二指肠穿孔等药品说明书未记载的
(3):826-832.
ADR,以确保临床安全用药。 [13] SEEGOBIN K,MAJEED U,LOU Y,et al. Patients with
参考文献 high-grade alectinib-induced skin rash:how do we desen-
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中国药房 2021年第32卷第16期 China Pharmacy 2021 Vol. 32 No. 16 ·2023 ·