Serum level changes of matrix metalloproteinases 2 and 9, vascular endothelial growth factor and epidermal growth factor receptor during platinum-based chemotherapy in advanced non-small cell lung cancer patients.
OBJECTIVE
To evaluate serum changes of matrix metalloproteinases (MMPs) 2 and 9, vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) levels in patients with advanced non-small cell lung cancer (NSCLC) and their association with main clinicopathological parameters during chemotherapy with cisplatin and gemcitabine.


METHODS
In this prospective study, consecutive patients with stage III and IV NSCLC were enrolled. Serum MMP2 and 9, VEGF and EGFR levels were monitored in blood samples taken on day 1 of starting chemotherapy (baseline 1st), and after 3 cycles of chemotherapy (2nd) using commercial sandwich ELISA method.


RESULTS
116 patients were evaluated. Males / females 100 / 6, ECOG performance status (PS) 0/1/2: 47/65/4, stage III / IV: 49/67, squamous /adeno/large cell carcinoma 41/31/19. Forty-two (36%) patients achieved partial response (PR), 32 (28%) stable disease (SD) and 42 (36%) showed progressive disease (PD). Mean serum values -/+ standard deviation (SD) of the analyzed markers at baseline/at response evaluation were: EGFR 86 -/+ 87/96 -/+ 47 fmol/ml; MMP9 236 -/+ 156/162 -/+ 133 ng/ml ; MMP2 525 -/+ 189/569 -/+ 201 ng/ml; VEGF 555 -/+ 476/599 -/+ 611 pg/ml; VEGF adjusted for platelets (PLT) 1.9 -/+ 1.45/2.4 -/+ 2.78 pg/10(6). In logistic regression model for response rate adjusted for stage, the increase in MMP9 levels during chemotherapy (mean = 74 ng/ml -/+ SD 140) was predictive for progression (p=0.041) with 5% increase in the odds of progression for an increase of 10 ng.


CONCLUSIONS
MMP9 level increase was found to be predictive of disease progression. EGFR levels could refl ect extracellular domain (ECD) loss from resistant cells and its shedding into the circulation.
Mihaylova
Zh
Zh
Department of Hematology and Oncology, Military Medical Academy, Sofia, Bulgaria. zhasminam@yahoo.com
Ludovini
V
V
Gregorg
V
V
Floriani
I
I
Pistola
L
L
Toffaneti
Fr
F
Ferraldeschi
M
M
Spreafico
A
A
Ceresoli
G L
GL
Bellet
M
M
Darwish
S
S
Tonato
M
M
Raynov
J
J
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D066246:ErbB Receptors / Q000097:blood*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D040262:Receptors, Vascular Endothelial Growth Factor / Q000097:blood*; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D002945:Cisplatin; D000093542:Gemcitabine