• S Zeamari, B Floot, N van der Vange, and F A Stewart.
• Department of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
• Anticancer Res. 2003 Mar 1; 23 (2B): 1643-8.

BackgroundHIPEC is a new treatment modality for abdominal cancers that combines cytoreductive surgery with Hyperthermic, Intraoperative Peritoneal Chemotherapy, followed by systemic chemotherapy. A significant survival benefit has been shown for HIPEC compared with systemic therapy alone. However, it is not clear what is the contribution of i.p. drug delivery and what influence the mild hyperthermia has on the uptake of cisplatin in abdominal tumors.Materials And MethodsWe used a peritoneal perfusion system in rats to compare the pharmacokinetics and pharmacodynamics of cisplatin, after normothermic (37 degrees C/90 minutes) and hyperthermic (40 degrees C/90 minutes) intra-peritoneal perfusion, with an i.p. bolus injection.ResultsHyperthermic perfusion with 15 micrograms/ml (in 200 ml) cisplatin gave equivalent plasma drug levels to a maximum tolerated dose (MTD) i.p. bolus injection of 4 mg/kg (36 micrograms/ml in 20 ml). The drug concentration in small (1-5 mm) intra-peritoneal tumors was also comparable for both these treatments, and for normothermic perfusion.ConclusionMild hyperthermic perfusion with cisplatin (40 degrees C/90 minutes) did not improve drug uptake in small intra-peritoneal tumors, relative to normothermic perfusion or i.p. bolus injection.

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