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

Int J Hyperthermia. 2009 Mar;25(2):132-40. doi: 10.1080/02656730802520697.

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 x 10(3)). Interleukin-2 (4.1 x 10(4) 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 degrees C or 43 degrees 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 degrees C = 29.88, 199.32, and 108.52, ILS% - 43 degrees 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.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Body Temperature
  • Carcinoma / therapy*
  • Chemotherapy, Cancer, Regional Perfusion*
  • Combined Modality Therapy
  • Disease Models, Animal
  • Female
  • Humans
  • Hyperthermia, Induced / methods*
  • Immunotherapy / methods
  • Interleukin-2 / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred CBA
  • Neoplasm Transplantation
  • Peritoneal Neoplasms / therapy*
  • Survival Rate
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Interleukin-2