Reduction of carcinomatosis risk using icodextrin as a carrier solution of intraperitoneal oxaliplatin chemotherapy

Eur J Surg Oncol. 2017 Jun;43(6):1088-1094. doi: 10.1016/j.ejso.2016.12.009. Epub 2017 Jan 9.

Abstract

There is no standard treatment in patients with high risk metachronous peritoneal carcinomatosis (PC) in colonic cancer, as perforated tumour or synchronous ovarian metastasis. Icodextrin 4% (ICDX), presently used to prevent postoperative abdominal adhesions, could inhibit the coactivation of the tumour cells and the microenvironment cells, associated with the development of PC. The aim of this study was to inhibit the formation of the PC in a murine model mimicking surgical situation using ICDX and intraperitoneal (IP) prophylactic chemotherapy. We created a model of growing PC in mice using cells of murine colonic cancer CT26. Cells and treatments were injected simultaneously. Five groups were created: CT26 (control group), CT26 + ICDX (ICDX group), CT26 + chemotherapy (oxaliplatin and 5FU) (chemo group), CT26 + chemotherapy + ICDX (ICDX chemo group), ICDX (toxicity group). At day 15, PC was evaluated with rodents PCI. In the chemo group, PCI was significantly lower than in the control group (3.2 versus 8.4, p = 0.02). ICDX had a synergetic effect on PC with chemotherapy; indeed PCI in ICDX chemo group was lower than in chemo group (1.4 versus 3.2, p = 0.04). There was no morbidity linked to ICDX in toxicity group. Safety of ICDX needs to be verified, particularly on colonic anastomosis before ICDX associated to IP chemotherapy could be used as a preventive treatment of PC in high risk patients. This prophylactic treatment is easy to use and would be administrated at the end of a curative surgery for a colonic cancer.

Keywords: Carcinomatosis; Colon cancer; Experimental study; Prophylactic treatment.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Carcinoma / drug therapy*
  • Carcinoma / secondary
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Dialysis Solutions / pharmacology*
  • Dialysis Solutions / therapeutic use
  • Disease Models, Animal
  • Fluorouracil / administration & dosage
  • Fluorouracil / pharmacology
  • Glucans / pharmacology*
  • Glucans / therapeutic use
  • Glucose / pharmacology*
  • Glucose / therapeutic use
  • Icodextrin
  • Infusions, Parenteral
  • Mice
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / secondary

Substances

  • Dialysis Solutions
  • Glucans
  • Organoplatinum Compounds
  • Oxaliplatin
  • Icodextrin
  • Glucose
  • Fluorouracil