Gemcitabine-induced severe pulmonary toxicity
Gemcitabine-induced severe pulmonary toxicity
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DOI：
10.1046/j.0767-3981.2003.00206.x
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发表时间：
2004-02-01
影响因子：
2.9
通讯作者：
Kleisbauer, JP
中科院分区：
文献类型：
--
作者：
Barlési, F;Villani, P;Kleisbauer, JP
吉西他滨是一种相对较新的脱氧胞苷类似物（2 '，2'-二氟脱氧胞苷），与阿糖胞苷（Ara-C）具有结构相似性。吉西他滨的活性在许多实体瘤的治疗中得到证实，如胰腺癌、卵巢癌和非小细胞肺癌（NSCLC）。尽管吉西他滨被认为是一种具有良好安全性特征的药物，但吉西他滨诱导的重度肺毒性（GISPT）病例与Ara-C相同。我们对GISPT上报告的病例进行了系统回顾。分析了29项临床试验，特别是关注的NSCLC患者（21）和21例报告病例，记录了40例患者。GISPT的发生率从0到5%不等。临床表现为亚急性临床综合征，通常是非特异性的。胸部X线主要表现为网状结节性间质浸润。GISPT的生理病理机制可能是由胆碱介导的肺泡毛细血管壁的炎症反应，导致肺泡毛细血管壁通透性异常。在排除鉴别诊断后，停药和早期开始使用类固醇和利尿剂是最常见的治疗方法。在这些条件下，大多数患者的结局是有利的，通常延迟几天，但20%的患者死亡。提出了既往肺部疾病或既往胸部放疗等发生GISPT的危险因素。GISPT是罕见的，但有时致命。有必要提高对它的认识，以加强对吉西他滨给药后发生这种毒性的患者的早期和适当的管理。
Gemcitabine is a relatively new deoxycytidine analog (2',2'-difluorodeoxycytidine) with structural similarities to cytosine arabinoside (Ara-C). Activity of gemcitabine is demonstrated in the treatment of many solid tumors, like pancreas, ovarian and nonsmall cell lung cancer (NSCLC). Although gemcitabine is considered as a drug with a good safety profile, cases of gemcitabine-induced severe pulmonary toxicity (GISPT) were reported as for Ara-C. We performed a systematic review of reported cases on the GISPT. Twenty-nine clinical trials especially interesting NSCLC patients (21) and 21 reported cases recording 40 patients were analyzed. The incidence of the GISPT varies from 0 to 5%. The clinical presentation is a subacute clinical syndrome and is frequently nonspecific. The predominant radiographic pattern on chest X-ray are reticulo-nodular interstitial infiltrates. It was postulated that the physio-pathological mechanism of the GISPT was an inflammatory reaction of the alveolar capillary wall cytokine-mediated, which created an abnormal permeability of its membrane. After the differential diagnosis were ruled out, the discontinuation of the drug and the early initiation of steroids and diuretics are the most frequently performed treatments. Under these conditions, the outcome was favorable in a delay of few days generally for a majority of patients but 20% of patients died. Some risk factors, as a previous pulmonary disease or a previous thoracic irradiation, for the occurrence of the GISPT were proposed. GISPT is rare but sometimes fatal. its a necessity to increase awareness about it to enhanced an early and suitable management of patients developing such a toxicity after gemcitabine administration.