Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib.
OBJECTIVE
Interstitial lung disease (ILD) is a serious adverse effect of gefitinib, but its prevalence and risk factors remain largely unknown. We examined the prevalence of and risk factors for gefitinib-induced ILD associated with practical use of the drug in Japanese with non-small-cell lung cancer (NSCLC).


METHODS
Clinical information was retrospectively assembled for NSCLC patients who started gefitinib treatment at affiliated institutions of the West Japan Thoracic Oncology Group between August 31 and December 31, 2002. Medical records of patients who developed pulmonary infiltrates were reviewed by a central committee of extramural experts for identification of patients with gefitinib-induced ILD. Multivariate logistic or Cox regression analysis was performed to identify independent predictive factors for ILD, antitumor response, and survival.


RESULTS
Seventy cases of and 31 deaths from gefitinib-induced ILD were identified among 1,976 consecutively treated patients at 84 institutions, corresponding to a prevalence of 3.5% and mortality of 1.6%. Gefitinib-induced ILD was significantly associated with male sex, a history of smoking, and coincidence of interstitial pneumonia (odds ratios = 3.10, 4.79, and 2.89, respectively). Predictive factors for response were female sex, no history of smoking, adenocarcinoma histology, metastatic disease, and good performance status (PS), whereas predictive factors for survival were female sex, no history of smoking, adenocarcinoma histology, nonmetastatic disease, good PS, and previous chest surgery.


CONCLUSIONS
ILD is a serious adverse effect of gefitinib in the clinical setting that cannot be ignored. However, patient selection based on sex and smoking history can minimize ILD risk and maximize the clinical benefit of gefitinib.
Ando
Masahiko
M
Department of Preventive Services, Kyoto University School of Public Health, Kyoto, Japan. mando@kuhp.kyoto-u.ac.jp
Okamoto
Isamu
I
Yamamoto
Nobuyuki
N
Takeda
Koji
K
Tamura
Kenji
K
Seto
Takashi
T
Ariyoshi
Yutaka
Y
Fukuoka
Masahiro
M
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D000077156:Gefitinib; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D017563:Lung Diseases, Interstitial / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib