Immunological and angiogenic markers during metronomic temozolomide and cyclophosphamide in canine cancer patients

Metronomic chemotherapy stimulates the immune response via depletion of regulatory T cells (Tregs) and suppresses angiogenesis by modulating the secretion of thrombospondin-1 (TSP-1) and vascular endothelial growth factor (VEGF). In this study, blood was collected from 10 healthy dogs and from 30 canine cancer patients before and 2 and 4weeks after treatment with metronomic temozolomide (6.6mgm−2), cyclophosphamide (12.5mgm−2) or cyclophosphamide and temozolomide. The percentage of circulating CD25+Foxp3+CD4+ Tregs and the plasma levels of TSP-1 and VEGF were measured. There was a significant difference in the percentage of Tregs between cancer patients and healthy dogs. A significant decrease in Tregs was noted in patients treated with metronomic cyclophosphamide and the combination. Treatment with temozolomide had no effect on the percentage of Tregs. TSP-1 and VEGF levels were, respectively, significantly lower and higher in cancer patients than in healthy dogs, but they were not influenced by any of the studied metronomic treatment regimens