title: Risk factors for interstitial lung disease and predictive factors for tumor response in patients with advanced non-small cell lung cancer treated with gefitinib.
abstract: A high incidence of interstitial lung disease (ILD) has been reported in patients with non-small cell lung cancer (NSCLC) treated with gefitinib in Japan. We retrospectively analyzed 112 patients with advanced NSCLC who received gefitinib monotherapy. Univariate and multivariate analyses were used to identify risk factors for gefitinib-related ILD and predictive factors for tumor response to gefitinib. The incidence of ILD was 5.4%, and it was higher in the patients with pre-existing pulmonary fibrosis (33% versus 2%; P < 0.001). The results of a multivariate analysis showed that pulmonary fibrosis was a significant risk factor for ILD (odds ratio: 177, 95% confidence interval: 4.53-6927, P = 0.006). The response rate was 33% in the 98 evaluable patients and higher in women (53% versus 23%; P = 0.003), patients with adenocarcinoma (38% versus 6%; P = 0.010), never-smokers (63% versus 18%; P < 0.001), and the patients with no history of thoracic radiotherapy (39% versus 13%; P = 0.015). The results of a multivariate analysis showed that the predictors of tumor response were "no history of smoking" and "no history of thoracic radiotherapy". Never-smokers had a significantly longer survival time than smokers (P = 0.007). Although gefitinib therapy confers a clinical benefit on patients with advanced NSCLC, especially on women, patients with adenocarcinoma, never-smokers, and patients with no history of thoracic radiotherapy, it also poses a high risk of ILD, especially to patients with pulmonary fibrosis. The risk-benefit ratio must be carefully considered.
authors.affiliation: Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. totakano@ncc.go.jp
authors.forename: Toshimi
authors.initials: T
authors.lastname: Takano
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kusumoto
authors.forename: Ukihide
authors.initials: U
authors.lastname: Tateishi
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sekine
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kodama
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
mesh_terms: D000230:Adenocarcinoma / Q000150:complications* / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications* / Q000188:drug therapy*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000209:etiology*; D008175:Lung Neoplasms / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011799:Quinazolines / Q000009:adverse effects* / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib