Prevention of peritoneal carcinomatosis in mice with combination hyperthermal intraperitoneal chemotherapy and IL-2

Abstract

Purpose: The purpose of this study was to investigate the effect of local chemoimmunotherapy and hyperthermal intraperitoneal chemotherapy (HIPEC) in a mouse model of induced peritoneal carcinomatosis.Material and methods: Peritoneal carcinomatosis in mice was produced by intraperitoneal implantation of MCa cells (5 × 103). Interleukin-2 (4.1 × 104 IU/mouse) was injected into the abdominal cavity of mice at day 7 and 3 before implantation of tumour cells. Immediately after implantation of MCa cells mice were treated twice with 2 ml of saline that was heated either at 37°C or 43°C and cytostatics (doxorubicin 20 mg kg−1, cisplatin 10 mg kg−1, mitomycin 5 mg kg−1, or 5-FU 150 mg kg−1). We followed the survival of animals and side effects appearing with different forms of treatment.Results: Combined treatment with Interleukin-2 (IL-2) and cytostatics (5-FU, CIS or MIT) significantly affected the development of peritoneal carcinomatosis and increased the survival of mice (ILS% – 37°C = 29.88, 199.32, and 108.52, ILS% – 43°C = 62.69, 260.50, and 178.05, respectively). However, intraperitoneal chemotherapy on survival time of mice with DOX + IL-2 was ineffective as compared with DOX alone.Conclusion: We would like to stress that treatment with IL-2 prior to tumour diagnosis is not clinically practical, rather, the manuscript attempts to describe an experimental proof of principle. Results suggest the synergistic effect of hyperthermia, chemotherapy and immunotherapy; IL-2 significantly increases antitumor activity of hyperthermic chemotherapy and survival rate of mice with peritoneal carcinomatosis.