Impact of preexisting pulmonary fibrosis detected on chest radiograph and CT on the development of gefitinib-related interstitial lung disease.
OBJECTIVE
Although preexisting pulmonary fibrosis (PF) on chest radiograph is known to be a risk factor of gefitinib-related interstitial lung disease (ILD), the significance of PF detected by chest computed tomography (CT) on the development of gefitinib-related ILD has not been investigated sufficiently.


METHODS
We reviewed 182 nonsmall cell lung cancer patients treated with gefitinib between July 2002 and March 2003. Chest radiographs and CT were taken in all patients periodically and reviewed by radiologists. PF was defined as ground-glass attenuation, consolidation, or reticular shadow without segmental distribution. Gefitinib-related ILD was defined as the acute respiratory failure developed during the course of gefitinib administration and lack of evidence for other cause of respiratory failure. Expected risk factors for gefitinib-related ILD were evaluated in multivariate analysis.


RESULTS
There were 15 patients with PF. Nine PF were detected on both chest radiograph and chest CT, and 6 on only chest CT. Twelve patients (6.6%) developed ILD during the course of gefitinib monotherapy and 4 died of it. Univariate and multivariate analyses showed that PF detected on chest radiograph was found to be the only significant risk factor for developing ILD (32.2, P < 0.001). Preexisting fibrosis diagnosed on chest CT but not apparent on chest radiograph was not significantly correlated with ILD.


CONCLUSIONS
Gefitinib should not be given to patients with PF apparent on chest radiograph. Patients with PF on chest CT but not detected on chest radiograph could be treated carefully with gefitinib, but a risk-benefit analysis should be considered.
Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. ynaito@east.ncc.go.jp
Yoichi
Y
Naito
Satoshi
S
Tsuchiya
Shinichi
S
Ishihara
Koichi
K
Minato
Yoshinori
Y
Shitara
Atsushi
A
Takise
Tatsuo
T
Suga
Akira
A
Mogi
Katsumi
K
Yamabe
Ryusei
R
Saito
D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011658:Pulmonary Fibrosis / Q000150:complications / Q000000981:diagnostic imaging*; D011799:Quinazolines / Q000009:adverse effects*; D013902:Radiography, Thoracic; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib