Comparative efficacy evaluation of catheter intraperitoneal chemotherapy,normothermic and hyperthermic chemoperfusion in a rat model of ascitic ovarian cancer

Objectives: The choice of an optimal administration route for intraperitoneal (IP) chemotherapy and a suitable chemotherapeutic regime in the treatment of ovarian cancer remains a controversy. We investigated survival outcomes according to catheter intraperitoneal chemotherapy (CIPC), normothermic and hyperthermic chemoperfusion (NIPEC and HIPEC) with cytostatic drugs dioxadet and cisplatin in rats with transplantable ascitic ovarian cancer.

Methods: Ascitic liquid containing 1?×?10⁷ tumour cells was inoculated to female Wistar rats and 48?hours after rats received dioxadet and cisplatin at the maximum tolerated doses. Dioxadet at doses 1.5, 30 and 15?mg/kg and cisplatin at doses 4, 40 and 20?mg/kg body weight were administered for CIPC, NIPEC and HIPEC, respectively. Rats in the control groups received physiological saline and CIPC with physiological saline was regarded as the untreated control. The antitumor activity of the drugs was evaluated as an increase in average life expectancy (ALE). Analysis of the data was based primarily on Bayesian statistics and included Kaplan–Meier method, log-rank test and hazard ratio (HR) estimation.

Results: Compared to the untreated control CIPC, NIPEC and HIPEC with dioxadet significantly increased ALE by ₁₀13₁₆, ₆15₂₄ and _1.717₃₅ days, whereas with cisplatin by ₆10₁₃, ₁₂24₃₇ and _–135₂₃ days, respectively.

Conclusions: Dioxadet and cisplatin show similar efficacy in the CIPC route. Compared with CIPC IP chemotherapy by chemoperfusions is more effective for both the drugs. Dioxadet in HIPEC showed highest survival benefit whereas largest effect during NIPEC is achieved with cisplatin.