Gefitinib-induced Interstitial Lung Disease in Korean Lung Cancer Patients

Abstract

Background Gefitinib is effective in the treatment of advanced non-small cell lung cancer (NSCLC), especially in patients harboring an epidermal growth factor receptor (EGFR) gene mutation. Interstitial lung disease (ILD) is a serious adverse effect of gefitinib, but its incidence and risk factors are not clearly defined yet. We examined the incidence and clinical characteristics of drug-induced ILD in Korean NSCLC patients treated with gefitinib.

Patients and methods A retrospective cohort study was performed in NSCLC patients who started gefitinib treatment at Seoul National University Hospital from January 2002 through December 2011. Patients who developed new abnormal radiologic findings with respiratory symptoms after gefitinib treatment were defined as having possible adverse pulmonary reactions. The patients medical records were reviewed independently by investigators to identify the causes of pulmonary toxicities. Multivariate logistic regression analyses were performed to identify independent predictive factors for gefitinib-induced ILD.

Results Among the 1,114 patients evaluated, 128 (11.5%) patients developed pulmonary adverse reactions after taking gefitinib. An infectious complication occurred in 98 (8.8%) patients and 15 (1.3%) patients developed ILD. Nine (60.0%) of the 15 patients with gefitinib-induced ILD experienced a fatal clinical course that met the Common Terminology Criteria for Adverse Events (CTCAE) grade 4 (n = 3) or grade 5 (n = 6). Twelve (80.0%) of 15 patients developed ILD in the first 8 weeks of gefitinib administration. In multivariate analysis, a lower serum albumin level at the time of gefitinib initiation was significantly associated with the development of gefitinib-induced ILD (odds ratio = 0.46

95% confidence interval: 0.22 – 0.98, P = 0.045).

Conclusions The incidence of gefitinib-induced ILD in Korean NSCLC patients was similar to that reported worldwide, but lower than values reported for other Asian populations. ILD is usually a life-threatening adverse effect of gefitinib and the development of ILD should be monitored closely, particularly among patients with a low serum albumin level.