Influence of CAP-regimen poly- and autohemochemotherapy on oxygen-dependent cytotoxicity of neutrophils in experimental ovarian cancer

Ovarian cancer is a topical issue of modern gynecological oncology. Every year 13,2 thousand of ovarian tumors and 7,7 lethal outcomes on account of such tumors are registered in Russia. Chemotherapy is the second major component of the treatment for ovarian cancer. However, cytostatic therapies are cancelled almost in every fourth patient due to the severity of side effects. The method of autohemochemotherapy (AHCT) providing blood cells reinfusion after their incubation with cytostatic drug, has lower dose-dependent toxicity and higher anti-tumor efficacy compared to polychemotherapy (PCT) with traditional solvents. The objective of the study was to evaluate the influence of CAP-regimen PCT and AHCT on oxygen-dependent cytotoxicity of neutrophils in experimental ovarian cancer. Materials and Methods. The study was performed on white rats weighing 180-200 g. Animals with transplanted ovarian ascitic tumors were treated with cytotoxic agents administered according to monotherapy schemes and CAP-scheme by AHCT and PCT. Such drugs as doxorubicin («Ebewe», Austria), cyclophosphamide («CONPO», Russia) and cisplatin («LENS-FARM», Russia) were used. The doses were calculated according to the nomogram per m2 of the animal's body surface area; doxorubicin dasage was 40 mg/m2, cyclophosphamide dosage - 600 mg/m2 and cisplatin dosage - 75 mg/m2. Blood for neutrophil studies was taken at 3- and 8-day after the chemotherapy drug administration. Myeloperoxidase (MPO) activity and the proportion of active neutrophils (PAN) in a spontaneous version of NBT-test were detected cytochemically. Methods of nonparametric statistics were used to process the obtained data. Results. It was found out that AHCT method as compared to conventional intravenous cytostatic administration led to severe neutropenia as early as on the third day after administration. Thus, the MPO-dependent and MPO-independent bactericidity increased when using CAP scheme.