Ando Masahiko, Okamoto Isamu, Yamamoto Nobuyuki, Takeda Koji, Tamura Kenji, Seto Takashi, Ariyoshi Yutaka, Fukuoka Masahiro
Department of Preventive Services, Kyoto University School of Public Health, Kyoto, Japan.
J Clin Oncol. 2006 Jun 1;24(16):2549-56. doi: 10.1200/JCO.2005.04.9866.
Interstitial lung disease (ILD) is a serious adverse effect of gefitinib, but its prevalence and risk factors remain largely unknown. We examined the prevalence of and risk factors for gefitinib-induced ILD associated with practical use of the drug in Japanese with non-small-cell lung cancer (NSCLC).
Clinical information was retrospectively assembled for NSCLC patients who started gefitinib treatment at affiliated institutions of the West Japan Thoracic Oncology Group between August 31 and December 31, 2002. Medical records of patients who developed pulmonary infiltrates were reviewed by a central committee of extramural experts for identification of patients with gefitinib-induced ILD. Multivariate logistic or Cox regression analysis was performed to identify independent predictive factors for ILD, antitumor response, and survival.
Seventy cases of and 31 deaths from gefitinib-induced ILD were identified among 1,976 consecutively treated patients at 84 institutions, corresponding to a prevalence of 3.5% and mortality of 1.6%. Gefitinib-induced ILD was significantly associated with male sex, a history of smoking, and coincidence of interstitial pneumonia (odds ratios = 3.10, 4.79, and 2.89, respectively). Predictive factors for response were female sex, no history of smoking, adenocarcinoma histology, metastatic disease, and good performance status (PS), whereas predictive factors for survival were female sex, no history of smoking, adenocarcinoma histology, nonmetastatic disease, good PS, and previous chest surgery.
ILD is a serious adverse effect of gefitinib in the clinical setting that cannot be ignored. However, patient selection based on sex and smoking history can minimize ILD risk and maximize the clinical benefit of gefitinib.
间质性肺病（ILD）是吉非替尼的一种严重不良反应，但其发生率及危险因素仍大多未知。我们研究了在日本非小细胞肺癌（NSCLC）患者中实际使用吉非替尼时，吉非替尼诱发的ILD的发生率及危险因素。
回顾性收集了2002年8月31日至12月31日在西日本胸部肿瘤学组下属机构开始接受吉非替尼治疗的NSCLC患者的临床信息。由校外专家中央委员会对出现肺部浸润的患者病历进行审查，以确定吉非替尼诱发的ILD患者。进行多因素逻辑回归或Cox回归分析，以确定ILD、抗肿瘤反应和生存的独立预测因素。
在84家机构连续接受治疗的1976例患者中，确诊70例吉非替尼诱发的ILD，其中31例死亡，发生率为3.5%，死亡率为1.6%。吉非替尼诱发的ILD与男性、吸烟史以及间质性肺炎并存显著相关（比值比分别为3.10、4.79和2.89）。反应的预测因素为女性、无吸烟史、腺癌组织学类型、转移性疾病和良好的体能状态（PS），而生存的预测因素为女性、无吸烟史、腺癌组织学类型、非转移性疾病、良好的PS以及既往胸部手术史。
在临床环境中，ILD是吉非替尼的一种严重不良反应，不容忽视。然而，根据性别和吸烟史进行患者选择可将ILD风险降至最低，并使吉非替尼的临床获益最大化。
