Description:
<jats:p> e13066 </jats:p><jats:p> Background: Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies in order to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage (PKA) of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) and intravenous fluid (IVF) administration, by affecting intravascular volume, would correlate with PKA. Methods: On an IRB-approved study, we collected blood and peritoneal perfusate from 13 patients undergoing HIPEC with a set dose of 100 mg cisplatin (n=4) or a BSA-based dose of 250 mg/m<jats:sup>2</jats:sup> oxaliplatin (n=9), and measured Pt concentrations by Inductively Coupled Plasma Mass Spectrophotometry. Areas under concentration-time curves from 0-60 minutes (AUC0-60) were calculated by Trapezoidal Rule. PKA was calculated by (AUC0-60[peritoneal fluid]/AUC0-60[plasma]). Linear regression and Wilcoxon rank-sum test were performed using SAS. Results: Models with both BSA and IVF as predictors of PKA fit better than BSA alone for cisplatin (p=.022 vs. p=.076) but not for oxaliplatin (p=.119 vs. p=.037). The BSA and IVF model was a better fit for peritoneal cisplatin (p=.003) than for plasma cisplatin (p=.146). The BSA-only model was a better fit for plasma oxaliplatin (p=.013) than for peritoneal oxaliplatin (p=.778). There was no statistically-significant difference between the median PKA of cisplatin vs. oxaliplatin (p=.706). Conclusions: Our results suggest that BSA is a better PKA predictor than the compound’s diffusion properties. When a set drug dose is used, rather than a BSA-based dose, IVF is also an important predictor. This is likely due to HIPEC’s limited duration, thus the drug does not reach equilibrium between the peritoneal and vascular compartments. When monitoring the pharmacokinetic parameters of HIPEC administration, factors influencing intravascular volume, including BSA and IVF, should be considered. Maintaining intravascular volume repletion is a key strategy for maximizing PKA, and thereby minimizing systemic side effects due to HIPEC. </jats:p>