Comparative Study of Antitumor Efficiency of Intraperitoneal and Intravenous Cytostatics in Experimental Rats with Disseminated Ovarian Cancer

Abstract

Antitumor efficiencies of cytostatics dioxadet, cisplatin, mitomycin C, melphalan, and paclitaxel after a single intraperitoneal or intravenous injection in doses of 1.5, 4, 1.5, 2, and 5 mg/kg, respectively, were studied on the model of transplanted ovarian tumor in 124 rats. The antitumor effects were evaluated by the increase in median survival. Dioxadet, cisplatin, and melphalan injected intraperitoneally significantly prolonged the lifespan median - by 79, 88, and 114%, respectively, and were in fact ineffective, when injected intravenously. Intraperitoneal mitomycin C prolonged lifespan median by just 35%, intravenous - by 152%. Paclitaxel injected intraperitoneally and intravenously prolonged the lifespan median by 45 and 81%, respectively.

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

“…On the other hand, CIPC could be implemented at any stage of the treatment. Though less effective than NIPEC and HIPEC, the magnitude of survival benefit from CIPC is still much favourable compared to IV chemotherapeutic regimes as shown in our previous report [12]. In our study, rats treated by CIPEC with both cisplatin and dioxadet had a 66-85% increase in ALE (10 and 13 days).…”

“…The pronounced therapeutic efficacy of the drug is due to intramolecular crosslinking of the tumour cell DNA regardless of the cell cycle; low molecular weight, amphiphilic properties and slow clearance from the peritoneum [12]. According to our data, the largest efficacy of dioxadet could be achieved in HIPEC route.…”

“…Death of the animals in control without treatment occurred in 7-14 days after ovarian cancer inoculation. The ALE in the control without treatment accounted for 12 15 19 days. Contrarily, CIPC, NIPEC and HIPEC with dioxadet increased this rate by 13 (p ¼ 1.7 Â 10 À13 ), 15 (p ¼ 3.1 Â 10 À7 ) and 31 days (p ¼ 1.6 Â 10 À14 ) or 85%, 97% and 202%, respectively ( Table 2).…”

“…The diagnosis of ovarian cancer was confirmed by cytological examination of ascitic smear stained with haematoxylin and eosin. The methodology has been thoroughly described in our previous reports [12][13][14]. Nine rats died due to surgical complications and were excluded from the analysis.…”

“…Phase II clinical trial of dioxadet has demonstrated its pronounced antitumor efficacy during IV þ IP administration with dose-limiting but reversible myelosuppression in women with advanced EOCs [11]. Its ability to penetrate tumour tissue on direct contact as well as cellcycle independent activity leads to a renewed interest of dioxadet as a compound for IP regimes [11][12][13][14].…”