Harmonized statistical analysis of the efficacy of intraperitoneal chemotherapy regimens with dioxadet on ascitic ovarian cancer model

Abstract

A comparative statistical study of the results of eight independent experiments on the efficacy of intraperitoneal chemotherapy has been performed. The regiments of cathether intraperitoneal chemotherapy (CIPC), normothermic and hyperthermic chemoperfusion (NIPEC and HIPEC) with antitumor drug dioxadet were investigated in 288 female Wistar rats with ascitic ovarian cancer. Ovarian cancer was transplanted intraperitoneally (i.p.) 48 hours prior to a single chemotherapy at a number of 1><107 tumor cells. Dioxadet was administered at the maximum tolerated doses: CIPC - via syringe - 1.5 mg/kg body weight; NIPEC (36,5-37,5°C) and HIPEC (40,5-41,5°C) - infused for a continuous circulation using an experimental setting - at respective doses 30 and 15 mg/kg body weight. The rats in the control groups were administered in the same manner with physiological saline solution. The antitumor effects of the treatment were estimated as an increase in survival time. The statistical analysis was based on the principles of harmonization of statistical evidence and predictions. The mean survival time in the control group without treatment (i.p. saline injection) was 15 days with 95% confidence interval (CI) from 12 to 19 days. IPC, NIPEC and HIPEC increased mean survival time by 85, 97 and 202% (p<0.001 for the all cases) compared to the control group without treatment. Thus, HIPEC is the most effective mode of i.p. chemotherapy with antitumor drug dioxadet.