Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study.
BACKGROUND
Interstitial lung disease (ILD) occurs in Japanese patients with non-small cell lung cancer (NSCLC) receiving gefitinib.


OBJECTIVE
To elucidate risk factors for ILD in Japanese patients with NSCLC during treatment with gefitinib or chemotherapy.


METHODS
In a prospective epidemiologic cohort, 3,166 Japanese patients with advanced/recurrent NSCLC were followed for 12 weeks on 250 mg gefitinib (n = 1,872 treatment periods) or chemotherapy (n = 2,551). Patients who developed acute ILD (n = 122) and randomly selected control subjects (n = 574) entered a case-control study. Adjusted incidence rate ratios were estimated from case-control data by odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression. Crude (observed) incidence rates and risks were calculated from cohort data.


RESULTS
The observed (unadjusted) incidence rate over 12 weeks was 2.8 (95% CI, 2.3-3.3) per 1,000 person-weeks, 4.5 (3.5-5.4) for gefitinib versus 1.7 (1.2-2.2) for chemotherapy; the corresponding observed naive cumulative incidence rates at the end of 12-week follow-up were 4.0% (3.0-5.1%) and 2.1% (1.5-2.9%), respectively. Adjusted for imbalances in risk factors between treatments, the overall OR for gefitinib versus chemotherapy was 3.2 (1.9-5.4), elevated chiefly during the first 4 weeks (3.8 [1.9-7.7]). Other ILD risk factors in both groups included the following: older age, poor World Health Organization performance status, smoking, recent NSCLC diagnosis, reduced normal lung on computed tomography scan, preexisting chronic ILD, concurrent cardiac disease. ILD-related deaths in patients with ILD were 31.6% (gefitinib) versus 27.9% (chemotherapy); adjusted OR, 1.05 (95% CI, 0.3-3.2).


CONCLUSIONS
ILD was relatively common in these Japanese patients with NSCLC during therapy with gefitinib or chemotherapy, being higher in the older, smoking patient with preexisting ILD or poor performance status. The risk of developing ILD was higher with gefitinib than chemotherapy, mainly in the first 4 weeks.
Kudoh
Shoji
S
Nippon Medical School, Tokyo, Japan.
Kato
Harubumi
H
Nishiwaki
Yutaka
Y
Fukuoka
Masahiro
M
Nakata
Kouichiro
K
Ichinose
Yukito
Y
Tsuboi
Masahiro
M
Yokota
Soichiro
S
Nakagawa
Kazuhiko
K
Suga
Moritaka
M
Jiang
Haiyi
H
Itoh
Yohji
Y
Armour
Alison
A
Watkins
Claire
C
Higenbottam
Tim
T
Nyberg
Fredrik
F
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D016022:Case-Control Studies; D005260:Female; D000077156:Gefitinib; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000453:epidemiology* / Q000401:mortality; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011799:Quinazolines / Q000009:adverse effects*; D012307:Risk Factors
D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077156:Gefitinib