Interstitial lung disease in Japanese patients with lung cancer: A cohort and nested case-control study

Shoji Kudoh, Harubumi Kato, Yutaka Nishiwaki, Masahiro Fukuoka, Kouichiro Nakata, Yukito Ichinose, Masahiro Tsuboi, Soichiro Yokota, Kazuhiko Nakagawa, Moritaka Suga, Haiyi Jiang, Yohji Itoh, Alison Armour, Claire Watkins, Tim Higenbottam, Fredrik Nyberg, Takeshi Johkoh, Masashi Takahashi, Yoshiharu Ohno, Masahiko KusumotoHiroaki Arakawa, Fumikazu Sakai

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431 Citations (Scopus)


Rationale: Interstitial lung disease (ILD) occurs in Japanese patients with non-small cell lung cancer (NSCLC) receiving gefitinib. Objectives: 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. Measurements and Main 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.

Original languageEnglish
Pages (from-to)1348-1357
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number12
Publication statusPublished - 15-06-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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