Immunological aspects of metronomic chemotherapy regimens

Background. Metronomic chemotherapy regimens involving the continuous administration of chemotherapeutic agents in low doses may have additional clinical efficacy due to the activation of the antitumor immune response, while not leading to suppression of the functions of the immune system. Objective. Evaluation of the immunological efficacy of metronomic chemotherapy according to the cyclophosphamide+methotrexate (CM) regimen in combination with immunotherapy with the autologous dendritic cell vaccine CaTeVac in patients with soft tissue sarcomas (STS). Methods. The study included 25 patients with metastatic STS, who received CaTeVac in mono-regimen (n=13) in combination with metronomic therapy with cyclophosphamide and methotrexate (CaTeVac-CM) (n=12) as one of the stages of systemic treatment at the N.N. Petrov National Medical Research Center of Oncology in the 2013-2019. The immunological parameters and survival rates of this group of patients were assessed. Results. The only difference between the groups was found in the number of regulatory T-lymphocytes (T-reg), which significantly decreased during CaTeVac-CM therapy (p=0.0315). The median overall survival in patients receiving CaTeVac-CM was higher than in the group receiving only CaTeVac and amounted to 38.6 and 6.8 months, respectively (p=0.0074). The time to progression also significantly differed between groups and was 5.5 and 2.9 months, respectively (p=0.0416). Conclusion. The addition of metronomic chemotherapy according to the CM regimen to immunotherapy with the autologous dendritic cell vaccine CaTeVac increases the survival rates of patients by reducing the T-reg level. The combination of immunotherapy with metronomic chemotherapy may provide a new approach to the systemic therapy of patients with metastatic STS.

immunotherapy, autologous dendritic cell vaccine CaTeVac, metronomic chemotherapy