title: Interstitial lung disease associated with gemcitabine: A Japanese retrospective cohort study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hamada
authors.affiliation: Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yasunaga
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Nakai
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Isayama
authors.affiliation: Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Department of Health Care Informatics, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fushimi
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
mesh_terms: D000367:Age Factors; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000453:epidemiology*; D008175:Lung Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: adverse effect; drug therapy; gemcitabine; incidence; interstitial lung disease