Interstitial lung disease associated with gemcitabine: A Japanese retrospective cohort study

Interstitial lung disease (ILD) is a widely recognized adverse consequence of gemcitabine administration, but data on gemcitabine-associated ILD are limited. This study aimed to elucidate the incidence and risk factors for this adverse event.

Patients who underwent gemcitabine-based chemotherapy between July 2010 and March 2013 were retrospectively identified using a Japanese nationwide administrative database. ILD was defined according to the International Classification of Diseases and Related Health Problems 10th Revision, codes: J70.2-70.4, J84.1 and J84.9. The cumulative incidence and risk factors for ILD were evaluated using a competing risk analysis.

In total, 25 924 patients who underwent gemcitabine-based chemotherapy were identified from 331 hospitals (primary cancer; pancreatic, urothelial, biliary tract, lung, ovarian and breast, in 9070, 5578, 4803, 4388, 1339 and746 patients, respectively). ILD was observed in 428 patients (1.7%), and the cumulative incidence was estimated at 1.1% (95% CI: 1.0-1.2%), 1.5% (95% CI: 1.4-1.7%) and 1.9% (95% CI: 1.7-2.1%) at 3, 6 and 12 months, respectively. In the multivariable regression model, age >80 years and lung cancer were the strongest predictors for ILD (subdistribution hazard ratio (SHR), 2.61; 95% CI: 1.69-4.02 and SHR, 2.81; 95% CI: 2.16-3.65, respectively). Other significant risk factors included heavy smoking, prior chemotherapy and advanced cancer stage.

This study successfully demonstrated the clinical course of gemcitabine-associated ILD. Clinical oncologists should stratify individual patients for risk of ILD based on identified risk factors and fully consider the indication for gemcitabine-based chemotherapy.