Changes in angiogenic growth factor levels after gefitinib treatment in non-small cell lung cancer.
BACKGROUND
To investigate the changes in angiogenic growth factor expression before and after gefitinib treatment, and the association between this expression and response to gefitinib treatment, we measured circulating levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase (MMP) -2 and -9, and tissue inhibitors of metalloproteinase (TIMP) -1 and -2 in patients with non-small cell lung cancer (NSCLC).


METHODS
Serum and plasma samples were collected from 52 patients before and after gefitinib treatment. The levels of VEGF, bFGF, MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured using a sandwich enzyme immunoassay kit.


RESULTS
Of the 52 patients, 17 (32.7%) achieved a partial response, 19 (36.5%) had stable disease and 16 (30.8%) had progressive disease. The levels of VEGF, bFGF, MMP-2, MMP-9, TIMP-1 and TIMP-2 did not change significantly after gefitinib treatment, even in responders. The levels of VEGF in volunteers, responders and non-responders were 384 +/- 86.4, 404 +/- 94.3 and 719 +/- 99.8 pg/ml, respectively. The difference between volunteers and responders was not significant (P = 0.540), while the differences between volunteers and non-responders (P = 0.031), and responders and non-responders (P = 0.028) were significant.


CONCLUSIONS
Although our results indicate that gefitinib treatment does not affect circulating levels of angiogenic growth factors even in patients who showed a response to gefitinib treatment, low levels of VEGF may predict response to gefitinib treatment in patients with NSCLC.
Yoshimoto
Akihiro
A
Department of Hematology-Oncology and Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8641, Japan.
Kasahara
Kazuo
K
Nishio
Makoto
M
Hourai
Takeshi
T
Sone
Takashi
T
Kimura
Hideharu
H
Fujimura
Masaki
M
Nakao
Shinji
S
D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008875:Middle Aged; D011799:Quinazolines / Q000627:therapeutic use*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis
D043925:Angiogenesis Inducing Agents; D000970:Antineoplastic Agents; D011799:Quinazolines; D019715:Tissue Inhibitor of Metalloproteinase-1; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077156:Gefitinib