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PR063/#206  The role of hyperthermia in intraperitoneal chemotherapy on abdominal tissue concentrations of cisplatin – insights from a porcine model
  1. Christina Harlev,
  2. Mats Bue,
  3. Elisabeth Petersen,
  4. Andrea Jørgensen,
  5. Bo Bibby,
  6. Anne Schmedes,
  7. Maiken Stilling and
  8. Lone Petersen
  1. Aarhus University, Department of Clinical Medicine, Aarhus, Denmark

Abstract

Introduction In clinical studies cytoreductive surgery (CRS) combined with hyperterm intraperitoneal chemotherapy (HIPEC) utilizing cisplatin has revealed enhanced survival in patients with advanced ovarian cancer. One potential mechanism behind the effect of HIPEC is increased local penetration of chemotherapy. This study aims to examine the effect of hyperthermia during intraperitoneal chemotherapy on local abdominal tissue concentrations of cisplatin during and after HIPEC and normothermic intraperitoneal chemotherapy (NIPEC).

Methods We used microdialysis to dynamically sample tissue concentrations during and after HIPEC/NIPEC in a porcine model. All 16 pigs underwent CRS and were divided into two groups, receiving either CRS+HIPEC or CRS+NIPEC. Figure 1 shows the experimental timeline and sampling times. Table 1 shows sampling sites. The concentration of cisplatin in dialysate samples was determined by UPLC-MS/MS.

Abstract PR063/#206 Table 1

Results There was no statistical significant difference between the maximal concentration or area under the curve between the two groups. For both the HIPEC and NIPEC setup we found statistical significantly higher concentrations in the peritoneal compartments compared to all other compartments in terms of Cmax and AUC0-last

Conclusion/Implications Applying hyperthermia during intraperitoneal chemotherapy did not enhance cisplatin penetration or concentration in abdominal tissue in our study. It remains to be established whether HIPEC confers benefits compared to NIPEC beyond drug penetration by inducing other cytotoxic effects such as promoting apoptosis or impairing DNA repair mechanisms in cancer cells.

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