Interstitial Lung Disease in Japanese Patients with Lung Cancer: A Cohort and Nested Case-Control Study

• Published in: American journal of respiratory and critical care medicine Vol. 177; no. 12; pp. 1348 - 1357
• Main Authors: Kudoh, Shoji, Kato, Harubumi, Nishiwaki, Yutaka, Fukuoka, Masahiro, Nakata, Kouichiro, Ichinose, Yukito, Tsuboi, Masahiro, Yokota, Soichiro, Nakagawa, Kazuhiko, Suga, Moritaka, Japan Thoracic Radiology Group, Jiang, Haiyi, Itoh, Yohji, Armour, Alison, Watkins, Claire, Higenbottam, Tim, Nyberg, Fredrik
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.06.2008; American Lung Association; American Thoracic Society
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Case-Control Studies; Clinical death. Palliative care. Organ gift and preservation; Female; Humans; Incidence; Intensive care medicine; Japan - epidemiology; Kaplan-Meier Estimate; Logistic Models; Lung cancer; Lung Diseases, Interstitial - chemically induced; Lung Diseases, Interstitial - epidemiology; Lung Diseases, Interstitial - mortality; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Male; Medical sciences; Middle Aged; Prospective Studies; Protein Kinase Inhibitors - adverse effects; Quinazolines - adverse effects; Risk Factors; Japan; Antineoplastic agent; Intensive care; Quinazoline derivatives; Lung cancer; Case control study; non-small cell lung carcinoma; Cohort study; Bronchus disease; Gefitinib; Protein-tyrosine kinase; Resuscitation; Human; Lung disease; Enzyme; Tyrosine kinase inhibitor; Respiratory disease; Transferases; Enzyme inhibitor; Malignant tumor; Japanese; non-small cell lung cancer; interstitial lung disease; Japanese patients; gefitinib; Chemotherapy; Treatment; Interstitial pneumonitis; Cancer
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.200710-1501OC

Interstitial lung disease (ILD) occurs in Japanese patients with non-small cell lung cancer (NSCLC) receiving gefitinib. To elucidate risk factors for ILD in Japanese patients with NSCLC during treatment with gefitinib or chemotherapy. 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. 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). 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.