P3-1-1 - Efficacy of Intraperitoneal and Intravenous Administration of Antitumor Drugs in Rats with Peritoneal Carcinomatosis

Abstract

Background: Intraperitoneal (i.p.) chemotherapy in patients with peritoneal carcinomatosis could be an more effective treatment strategy than intravenous (i.v.) chemotherapy. The purpose of the study is to compare antitumor activity of different drugs at their i.p. and i.v. administration in rats with peritoneal carcinomatosis.Metods: The study was carried out in 100 Wistar female rats with ovarian cancer which was inoculated intraperitoneally (i.p.) to simulate peritoneal carcinomatosis. Transplanted epithelial ovarian cancer strain used was originated from the rat subjected to transplacental administration of 7,12-dimethylbenz(a)anthracene. After ovarian cancer inoculation rats were randomized in 10 groups, 10 rats in each group. There were five groups where saline (2 ml, i.p. control group) or the drugs (dioxadet 1.5 mg/kg, cisplatin 4mg/kg, melphalan 2 mg/kg, mitomycin C 1.5 mg/kg) were administered i.p. In other five groups saline (2 ml, i.v. control group) and the named above drugs at the same doses were administered i.v. Dioxadet is original Russian antineoplastic drug from the group of ethyleneimine alkylating agents. Antitumor effects of the treatment were estimated by increase in survival time (IST) comparing median survival time of rats in different groups.Results: IST for i.p. administration of dioxadet, cisplatin, melphalan and mitomycin C were 76.5% (p < 0.001), 91.1% (p < 0.001), 117.6% (p < 0.001) and 24% (p = 0.002) correspondingly compared to i.p. control group while for i.v. administration of these drugs IST were 5% (p = 0.796), 14.2% (p = 0.315), 19% (p = 0.631) and 152% (p < 0.001) correspondingly compared to i.v. control group. Thus, the only drug to provide significant antitumor action at i.v. administration was mitomycin C.Conclusion: I.p. chemotherapy with alkylating agents dioxadet, cisplatin and melphalan is much more effective then their i.v. administration while antitumor antibiotic mitomycin C is more active at i.v. administration.