Risk factors for interstitial lung disease and predictive factors for tumor response in patients with advanced non-small cell lung cancer treated with gefitinib.
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.
Takano
Toshimi
T
Division of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. totakano@ncc.go.jp
Ohe
Yuichiro
Y
Kusumoto
Masahiko
M
Tateishi
Ukihide
U
Yamamoto
Seiichiro
S
Nokihara
Hiroshi
H
Yamamoto
Noboru
N
Sekine
Ikuo
I
Kunitoh
Hideo
H
Tamura
Tomohide
T
Kodama
Tetsuro
T
Saijo
Nagahiro
N
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
D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib