title: Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study.
abstract: BACKGROUND
  Interstitial lung disease (ILD) occurs in Japanese patients with non-small cell lung cancer (NSCLC) receiving gefitinib.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Nippon Medical School, Tokyo, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.forename: Harubumi
authors.initials: H
authors.lastname: Kato
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nishiwaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Kouichiro
authors.initials: K
authors.lastname: Nakata
authors.forename: Yukito
authors.initials: Y
authors.lastname: Ichinose
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuboi
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yokota
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Moritaka
authors.initials: M
authors.lastname: Suga
authors.forename: Haiyi
authors.initials: H
authors.lastname: Jiang
authors.forename: Yohji
authors.initials: Y
authors.lastname: Itoh
authors.forename: Alison
authors.initials: A
authors.lastname: Armour
authors.forename: Claire
authors.initials: C
authors.lastname: Watkins
authors.forename: Tim
authors.initials: T
authors.lastname: Higenbottam
authors.forename: Fredrik
authors.initials: F
authors.lastname: Nyberg
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D016022:Case-Control Studies; D005260:Female; D000077156:Gefitinib; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000453:epidemiology* / Q000401:mortality; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011799:Quinazolines / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077156:Gefitinib