Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI)-Related Severe Interstitial Lung Disease in Taiwanese Patients with Non-Small Cell Lung Cancer

非小細胞癌患者使用表皮生長因子受體激酶抑制劑後發生嚴重間質性肺炎之研究

江起陸(Chi-Lu Chiang) ； 邱昭華(Chao-Hua Chiu) ； 李毓芹(Yu-Chin Lee) ； 蔡俊明(Chun-Ming Tsai) ； 吳杰鴻(Chieh-Hung Wu)

《胸腔醫學》 29卷6期 (2014/12) Pp. 335-343

摘要

前言：非小細胞肺癌是國人因癌症死亡最重要的原因之一。表皮生長因子受體激酶抑制劑的發現對晚期非小細胞肺癌的患者提供相當大的幫助；但其最嚴重的副作用為間質性肺炎。雖然罕見，但據國內外文獻指出具有高死亡率。國內目前對於表皮生長因子受體激酶抑制劑引起之間質性肺炎，其發生率及臨床特徵仍無深入研究。方法：以回溯性病例研究方法，搜集台北榮民總醫院過去病理或細胞學診斷為非小細胞肺癌的病患，其於表皮生長因子受體激酶抑制劑治療期間發生嚴重間質性肺炎之機率及臨床表現。結果：於2008年二月至2012年七月間，篩選本院1212位使用表皮生長因子受體激酶抑制劑的非小細胞肺癌病患,找出治療期間發生嚴重間質性肺炎而需要住院治療的患者。其中9位（0.7％）被診斷為表皮生長因子受體激酶抑制劑引起之間質性肺炎，服藥至發生間質性肺炎的時間之中位數為31天（10-75天）。在這九位患者中，最常見的臨床症狀為喘（88.9％），最常見的影像學變化為雙側毛玻璃狀病變（55.6％），其中六位病人因間質性肺炎死亡，死亡率為67％。結論：雖然罕見，表皮生長因子受體激酶抑制劑在國人仍可造成致命之間質性肺炎。臨床醫師在開立此藥時應密切監測和注意。

關鍵字

非小細胞肺癌 ； 表皮生長因子受體激酶抑制劑 ； 間質性肺炎

並列摘要

Background: It has been shown in recent years that epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), whether gefitinib or erlotinib, can provide significant benefit to patients with advanced non-small cell lung cancer (NSCLC). A major concern with EGFR-TKI treatment is the development of interstitial lung disease (ILD). The incidence and clinical characteristics of ILD associated with EGFR-TKIs in Taiwanese patients are less well defined. Methods: Patients with advanced NSCLC in Taipei Veterans' General Hospital were screened and those who had received an EGFR-TKI were enrolled in this study. Their clinical information, including medical records and chest images, was reviewed. The diagnosis of EGFR-TKI-related ILD was confirmed by 2 pulmonologists in accordance with previously published criteria. Association between ILD development and clinical factors was evaluated. Results: From February 2008 to July 2012, 1212 patients who received an EGFR-TKI as single therapy for NSCLC were screened. Patients who developed severe ILD and needed hospitalization (NCI CTC grade 3-5) were included. Nine of the 1212 patients (0.7%) were diagnosed as having severe EGFR-TKI-related ILD. The median time interval from EGFR-TKI use to onset of ILD was 31 days (range: 10-75 days). The most common symptom of EGFRTKI- related ILD was dyspnea (88.9%). The most common radiological manifestation was bilateral ground glass opacity, which was noted in 5 patients (55.6%). Six of the 9 patients (67%) died due to ILD. Conclusion: EGFR-TKIs, both gefitinib and erlotinib, may cause fatal ILD in Taiwanese NSCLC patients. Physicians should be aware of this rare side effect of EGFR-TKIs and monitor this pulmonary toxicity closely.

並列關鍵字

non-small cell lung cancer ； epidermal growth factor receptor ； tyrosine kinase inhibitor ； interstitial lung disease