The role of VEGF and other parameters in tracking the clinical course in metronomic chemotherapy.

PURPOSE: The purpose of this study was to investigate the effect of metronomic chemotherapy on serum vascular endothelial growth factor (VEGF) levels in cancer patients. METHODS: The study included 11 metastatic cancer patients who received daily 50 mg cyclophosphamide and biweekly 5 mg methotrexate per os as metronomic chemotherapy. Bevacizumab together with FOLFIRI chemotherapy was administered as anti-angiogenic treatment in another group of 16 metastatic colorectal carcinoma patients. Furthermore, VEGF levels of 10 healthy individuals and 5 cord blood samples served for comparisons. VEGF levels of patients before therapy and 3 months after treatment were analyzed and compared. RESULTS: Serum VEGF levels prior to metronomic chemotherapy were higher compared with the healthy controls (p=0.0001). Similarly, serum VEGF levels prior to the bevacizumab-based chemoimmunotherapy were significantly higher compared with the healthy controls (p=0.005). In patients on metronomic chemotherapy VEGF levels showed non significant decrease (p=0.075). On the contary, VEGF levels decreased significantly (p=0.002) with bevacizumab treatment. CONCLUSION: Serum VEGF levels may be used for assessing of the efficacy of anti-angiogenic therapies.

Cisplatin cytotoxicity is enhanced with zoledronic acid in A549 lung cancer cell line: preliminary results of an in vitro study.

We tested whether zoledronic acid, a biphosphonate with proposed apoptotic activity, augmented the cytotoxicity of cisplatin and/or gemcitabine in A549 lung cancer cell line. This cell line was subjected to different concentrations of the above chemotherapeutic agents and zoledronic acid. Cytotoxicity was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) assay. Particularly, zoledronic acid in 100 micromolar (microM) concentration augmented the cytotoxicity by cisplatin 1microg/ml from 25% to 70% (Z=3.22, P=0.0072). A significant portion of cells underwent apoptosis with or without zoledronic acid, but more so with the combination treatment as assessed by an Annexin V-FITC apoptosis detection kit. However, 100microM zoledronic acid showed 50% cytotoxicity on its own, but failed to improve cytotoxicity by Gemcitabine. Thus, we show for the first time in a lung cancer cell line that zoledronic acid bears cytotoxic potential on its own and in conjunction with cisplatin. The clinical potential of this finding should be further studied.