title: Association between baseline pulmonary status and interstitial lung disease in patients with non-small-cell lung cancer treated with erlotinib--a cohort study.
abstract: BACKGROUND
  Although interstitial lung disease (ILD) is a known serious adverse effect of epidermal growth factor receptor tyrosine kinase inhibitors, the risk factors for its development are poorly defined. To determine the risk factors for the development of drug-induced ILD and poor-prognosis (fatal) drug-induced ILD after erlotinib treatment, we assessed the baseline pulmonary status in patients with non-small cell lung cancer enrolled in a postmarketing clinical study of erlotinib.
  
  
  METHODS
  In the present prospective cohort study, the baseline pulmonary status of all patients was evaluated using conventional or high-resolution computed tomography. The patients were monitored for the development of drug-induced ILD for 120 days after the start of treatment. All diagnoses of drug-induced ILD were confirmed by an independent ILD safety review committee. The risk factors were determined using logistic regression analysis.
  
  
  RESULTS
  A total of 645 patients were enrolled, of whom 627 were evaluable. The committee confirmed the diagnoses of drug-induced ILD in 19 patients, 6 of whom had fatal outcomes. Multivariate logistic regression analysis revealed that pre-existing ILD and limited residual normal lung were significant risk factors for the development of drug-induced ILD. An additional multivariate logistic regression analysis revealed that limited residual normal lung was a significant risk factor for the development of poor-prognosis (fatal) drug-induced ILD.
  
  
  CONCLUSIONS
  Pre-existing ILD and the amount of residual normal lung (≤ 50%) were identified as risk factors for the development of drug-induced ILD. The amount of residual normal lung (≤ 50%) was identified as a risk factor for the development of poor-prognosis (fatal) drug-induced ILD.
authors.affiliation: Department of Radiology, Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Itami, Hyogo, Japan. Electronic address: johkoht@aol.com.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Johkoh
authors.affiliation: Department of Diagnostic Radiology, Saitama International Medical Center, Saitama Medical University, Hidaka, Saitama, Japan.
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Sakai
authors.affiliation: Department of Diagnostic Radiology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kusumoto
authors.affiliation: Department of Radiology, Dokkyo Medical University, Shimotsuga-gun, Tochigi, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Arakawa
authors.affiliation: Clinical Research Department, Chugai Pharmaceutical Co, Ltd, Chuo-ku, Tokyo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Harada
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co, Ltd, Chuo-ku, Tokyo, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Respiratory Medicine, Fukujuji Hospital, Kiyose, Tokyo, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: Department of Internal Medicine, Izumi Municipal Hospital, Izumi, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D015331:Cohort Studies; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000453:epidemiology*; D008175:Lung Neoplasms / Q000188:drug therapy*; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011799:Quinazolines / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D014057:Tomography, X-Ray Computed
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride
keywords: Baseline pulmonary status; Erlotinib; Interstitial lung disease; Non–small cell lung cancer