Takeshi Johkoh1, Fumikazu Sakai2, Masahiko Kusumoto3, Hiroaki Arakawa4, Ryosuke Harada5, Masamichi Ueda6, Shoji Kudoh7, Masahiro Fukuoka8. 1. Department of Radiology, Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Itami, Hyogo, Japan. Electronic address: johkoht@aol.com. 2. Department of Diagnostic Radiology, Saitama International Medical Center, Saitama Medical University, Hidaka, Saitama, Japan. 3. Department of Diagnostic Radiology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan. 4. Department of Radiology, Dokkyo Medical University, Shimotsuga-gun, Tochigi, Japan. 5. Clinical Research Department, Chugai Pharmaceutical Co, Ltd, Chuo-ku, Tokyo, Japan. 6. Clinical Research Planning Department, Chugai Pharmaceutical Co, Ltd, Chuo-ku, Tokyo, Japan. 7. Department of Respiratory Medicine, Fukujuji Hospital, Kiyose, Tokyo, Japan. 8. Department of Internal Medicine, Izumi Municipal Hospital, Izumi, Osaka, Japan.
Abstract
INTRODUCTION: 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. PATIENTS AND 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. CONCLUSION: 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.
INTRODUCTION: 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. PATIENTS AND 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. CONCLUSION: 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: Sarah Skeoch; Nicholas Weatherley; Andrew J Swift; Alexander Oldroyd; Christopher Johns; Conal Hayton; Alessandro Giollo; James M Wild; John C Waterton; Maya Buch; Kim Linton; Ian N Bruce; Colm Leonard; Stephen Bianchi; Nazia Chaudhuri Journal: J Clin Med Date: 2018-10-15 Impact factor: 4.241