Serum levels of surfactant protein D predict the anti-tumor activity of gefitinib in patients with advanced non-small cell lung cancer.
OBJECTIVE
Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that has dramatic effects in selective patients with non-small cell lung cancer (NSCLC). A simple non-invasive method for predicting the efficacy of gefitinib is preferable in clinical settings. In this study, we evaluated prospectively whether surfactant protein-A (SP-A) and -D (SP-D) may be new conventional predictors of the efficacy of gefitinib treatment.


METHODS
We measured serum SP-A and SP-D levels on days 0 and 29 in 40 patients with advanced NSCLC treated with 250 mg gefitinib daily. Eligibility criteria included performance status ≤3, age ≤80 years, and stage IIIB-IV disease. In addition, EGFR mutations were analyzed in 24 patients.


RESULTS
Multivariate analysis showed that favorable progression-free survival (PFS) after gefitinib treatment was associated with adenocarcinoma and high serum SP-D levels before treatment. EGFR mutation analysis of 24 patients showed that 16 patients had exon 19 deletion and/or exon 21 point mutations. EGFR mutations were significantly correlated with response to gefitinib and serum SP-D levels before treatment was significantly high in patients with the EGFR mutations. Serum SP-A levels were not associated with PFS.


CONCLUSIONS
The present study showed that measurement of serum SP-D levels before treatment in patients with NSCLC may be a new surrogate marker for predicting the response to gefitinib.
Yamaguchi
Hiroyuki
H
Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Soda
Hiroshi
H
Nakamura
Yoichi
Y
Takasu
Mineyo
M
Tomonaga
Nanae
N
Nakano
Hirofumi
H
Doi
Seiji
S
Nakatomi
Katsumi
K
Nagashima
Seiji
S
Takatani
Hiroshi
H
Fukuda
Minoru
M
Hayashi
Tomayoshi
T
Tsukamoto
Kazuhiro
K
Kohno
Shigeru
S
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D037662:Pulmonary Surfactant-Associated Protein A / Q000097:blood; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D047428:Protein Kinase Inhibitors; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib