ABSTRACT
1MedicalSchool Hospital “Santa Maria alle Scotte”, Oncology Unit,University of Siena
2Dep. of Neurological and Behavioural Science, “G.Segre” Pharmacology Unit, School of Medicine, University of Siena
Background: Bevacizumab is an anti-angiogenic humanized anti-VEGF mAb able to improve chemotherapy efficacy in advanced non-squamous non-small cell lung cancer (NSCLC), colorectal and breast cancer patients. VEGF acts by specific binding to multiple membrane receptors which are expressed on endothelial precursors as well as on other cell lineages including mesencephalic neurons, myeloid precursors, dendritic cells and lymphocytes. We therefore, investigated bevacizumab immune-modulating effects in advanced non-small-cell lung cancer patients, enrolled in an ongoing phase I-II trial. Material and methods: Twenty-five patients (20 males and 5 females) with stage IIIB/IV NSCLC enrolled in the phase II mPEBev study (EUDRACT#2008-00-6051-40) received every three weeks, iv. cisplatinum (30 mg/sqm, days 1-3), oral etoposide (50 mg, days 1-15) and bevacizumab (5 mg/kg, on day 3). These patients were evaluated for serum VEGF, IL-10, IL-4, IL-12, IFN-gamma, myeloperoxidase (MPO) and leptin concentration through ELISA assays. Furthermore, a cytometric analysis was done to evaluate neutrophils, lymphocytes, monocytes and platelets counts. We carried our immunological analysis at baseline and after they had received 4 cycles of treatment. Results: We observed a significant reduction in serum VEGF (p=0.003) and MPO (p= 0.026), and in lymphocytes (p=0.047), monocytes (p=0.008), neutrophils (p<0.001) and platelets (p<0.001). Moreover, IL-10 concentration was found to be higher than normal in all patients. No significant change were found in the others variables. Conclusions: These results indicate that Bevacizumab was able to reduce circulating VEGF and to impair neutrophils activity. Furthermore, we observed a stronger reduction in neutrophils and platelets counts, probably related to the capability of these cells to transport the majority of VEGF. On these basis, we hypothesize that selective bevacizumab-dependent reduction in circulating neutrophils and platelets may contribute to its antitumor effect.