Chimiothérapies hyperthermiques intra péritonéales (CHIP)

11 novembre 2010

J. Vandenbroucke UZ Gent, Belgique
Co-coordinateur « Standards of Practice » ISOPP

HYPEC is a intra peritoneal rinsing with cytotoxic drug under hyperthermia.

Intra operative IP cytotoxic therapy results in a definite pharmacological advantage, since high peritoneal concentrations are achieved with limited systemic absorption

Results from experiments with multicellular models have shown that direct tissue penetration of most cytotoxic agents is very limited in space (usually less than 1 mm). Intra peritoneal chemotherapy effectiveness will therefore be limited to tumour nodules of a very small dimension or to loose cancer cells.

Furthermore, the limited exposure time of intra operative chemo perfusion could limit cytotoxic activity despite high local concentrations.
Combining cytotoxic drug administration with hyperthermia results in increased uptake, probably related to membrane alterations
Among the cytotoxic agents currently used, the pharmacodynamic aspects of the platinum compounds are the best studied both with and without associated hyperthermia.

Newer agents such as the taxanes and the camptothecins appear promising for IP chemo perfusion during or immediately after surgery.

A rational choice of a cytotoxic agent for HIPEC therapy should consider the following
elements :

  • Activity against the disease process
  • Cell cycle specificity
  • Relation between dose / exposure time and response
  • Thermal enhancement ratio (when used in combination with hyperthermia)
  • Pharmacokinetic advantage (peritoneal/plasma AUC ratio)
  • Pharmacodynamic properties
  • Local and systemic toxicity

Attention also should be given to the vehiculum used in the intra peritoneal perfusion.
Since oxaliplatin can only be administered in a dextrose 5% solution, severe hyperglycaemia and hyponatriemia develops during chemo perfusion and continuous high dose insulin infusion has to be provided.

An overview of the UZ Gent experience with 130 patients treated will be given.

The technique used for this procedure is the coliseum technique.
Using this technique, the surgeons glove will be in contact with the drug for more the 30 minutes at a temperature of 41°C. This could lead to unacceptable skin contact of the surgeon to the cytotoxic drug.
Also considerations about evaporation have to be taken into account.
How it is performed and the materials used will be shown.

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