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

Purpose: 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. Patients and 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. Conclusion: 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.