Elevated serum level of sialylated glycoprotein KL-6 predicts a poor prognosis in patients with non-small cell lung cancer treated with gefitinib.
OBJECTIVE
The factors affecting survival after gefitinib treatment in patients with non-small cell lung cancer (NSCLC) remain to be fully elucidated, although epidermal growth factor receptor (EGFR) mutation is a substantial prognostic factor. KL-6 has been studied as a useful indicator for interstitial lung diseases; however, it was first discovered as a lung cancer-related antigen. The aim of this study was to investigate the prognostic value of the serum KL-6 levels in advanced NSCLC patients treated with gefitinib and thus determine its association with the EGFR mutation status.


METHODS
Between September 2002 and September 2005, 41 patients with NSCLC were treated with gefitinib after having their serum KL-6 levels measured at Okayama University Hospital. EGFR mutations were analyzed by direct sequence methods.


RESULTS
The serum KL-6 levels ranged from 199 to 9080U/ml (median, 550U/ml), and 54% of 41 patients showed a level higher than the cut-off level of 500U/ml. The median progression-free survival (PFS) time and the median overall survival (OS) time were 4.7 months and 13.9 months, respectively. Multivariate analyses revealed that the elevated KL-6 level was an independent adverse prognostic factor for PFS (hazard ratio: 2.278, p=0.040) as well as OS (hazard ratio: 4.858, p=0.002) in NSCLC patients treated with gefitinib. The EGFR mutation status was analyzed in 22 patients (54%). Among those with wild-type EGFR, the patients with high serum KL-6 levels also had a worse survival than those within normal serum KL-6 levels (6.5 months versus 13.3 months, p=0.0194).


CONCLUSIONS
Our data suggest that NSCLC patients with high serum KL-6 levels tended to have a poor clinical outcome when treated with gefitinib.
Fujiwara
Yoshiro
Y
Department of Hematology, Oncology and Respiratory Medicine, Okayama University Medical Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Kiura
Katsuyuki
K
Toyooka
Shinichi
S
Hotta
Katsuyuki
K
Tabata
Masahiro
M
Takigawa
Nagio
N
Soh
Junichi
J
Tanimoto
Yasushi
Y
Kanehiro
Arihiko
A
Kato
Katsuya
K
Date
Hiroshi
H
Tanimoto
Mitsune
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D009154:Mutation; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use*; D012189:Retrospective Studies
D000970:Antineoplastic Agents; C060192:MUC1 protein, human; D018396:Mucin-1; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib