Interstitial lung disease in Japanese patients with lung cancer - A cohort and nested case-control study
Interstitial lung disease in Japanese patients with lung cancer - A cohort and nested case-control study
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DOI：
10.1164/rccm.200710-1501oc
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发表时间：
2008-06-15
影响因子：
24.7
通讯作者：
Nyberg, Fredrik
中科院分区：
文献类型：
--
作者：
Kudoh, Shoji;Kato, Harubumi;Nyberg, Fredrik
目的：阐明日本非小细胞肺癌患者在接受吉非替尼治疗或化疗期间发生间质性肺疾病的危险因素。方法：在前瞻性流行病学队列中，3166名日本晚期/复发非小细胞肺癌患者接受吉非替尼250 mg(n=1,872个疗程)或化疗(n=2,551个疗程)12周的随访。发生急性ILD的患者(n=122)和随机选择的对照组(n=574)进入病例对照研究。调整后的发病率比根据病例对照数据通过Logistic回归的95%可信区间(CI)的优势比(OR)来估计。测量和主要结果：12周以上的观察(未调整)发病率为每千人周2.8(95%可信区间，2.3~3.3)，吉非替尼为4.5(3.5~5.4)，化疗组为1.7(1.2~2.2)；12周末观察到的幼稚累积发病率分别为4.0%(3.0-5.1%)和2.1%(1.5-2.9%)。调整了治疗之间危险因素的失衡，吉非替尼与化疗的总体OR为3.2(1.9-5.4)，主要在前4周(3.8[1.9-7.7])。两组中的其他ILD危险因素包括：年龄较大、世界卫生组织工作状况不佳、吸烟、最近诊断为非小细胞肺癌、CT扫描正常肺减少、既往存在慢性ILD、并发心脏病。ILD患者ILD相关死亡率为31.6%(吉非替尼)和27.9%(化疗组)；调整后OR为1.05(95%CI，0.3~3.2)。结论：ILD在接受吉非替尼治疗或化疗的日本非小细胞肺癌患者中相对常见，在老年、吸烟、既往存在ILD或表现不佳的患者中ILD发生率较高。服用吉非替尼的患者发生ILD的风险高于接受化疗的患者，主要发生在前4周。
Rationale: Interstitial lung disease (ILD) occurs in Japanese patients with non-small cell lung cancer (NSCLC) receiving gefitinib.Objectives: To elucidate risk factors for ILD in Japanese patients with NSCLC during treatment with gefitinib or chemotherapy.Methods: In a prospective epidemiologic cohort, 3,166 Japanese patients with advanced/recurrent NSCLC were followed for 12 weeks on 250 mg gefitinib (n = 1,872 treatment periods) or chemotherapy (n = 2,551). Patients who developed acute ILD (n = 122) and randomly selected control subjects (n = 574) entered a case-control study. Adjusted incidence rate ratios were estimated from case-control data by odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression. Crude (observed) incidence rates and risks were calculated from cohort data.Measurements and Main Results: The observed (unadjusted) incidence rate over 12 weeks was 2.8 (95% CI, 2.3-3.3) per 1,000 person-weeks, 4.5 (3.5-5.4) for gefitinib versus 1.7 (1.2-2.2) for chemotherapy; the corresponding observed naive cumulative incidence rates at the end of 12-week follow-up were 4.0% (3.0-5.1%) and 2.1% (1.5-2.9%), respectively. Adjusted for imbalances in risk factors between treatments, the overall OR for gefitinib versus chemotherapy was 3.2 (1.9-5.4), elevated chiefly during the first 4 weeks (3.8 [1.9-7.7]). Other ILD risk factors in both groups included the following: older age, poor World Health Organization performance status, smoking, recent NSCLC diagnosis, reduced normal lung on computed tomography scan, preexisting chronic ILD, concurrent cardiac disease. ILD-related deaths in patients with ILD were 31.6% (gefitinib) versus 27.9% (chemotherapy); adjusted OR, 1.05 (95% CI, 0.3-3.2).Conclusions: ILD was relatively common in these Japanese patients with NSCLC during therapy with gefitinib or chemotherapy, being higher in the older, smoking patient with preexisting ILD or poor performance status. The risk of developing ILD was higher with gefitinib than chemotherapy, mainly in the first 4 weeks.