Pharmacokinetics and pharmacodynamics of cisplatin after intraoperative hyperthermic intraperitoneal chemoperfusion (HIPEC)
Zeamari, S.; Floot, B.; van der Vange, N.; Stewart, F.A.
Anticancer Research 23(2b): 1643-1648
2003
ISSN/ISBN: 0250-7005 PMID: 12820435 Document Number: 556618
Background: HIPEC 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 Methods: We used a peritoneal perfusion system in rats to compare the pharmacokinetics and pharmacodynamics of cisplatin, after normothermic (37degreeC/90 minutes) and hyperthermic (40degreeC/90 minutes) intra-peritoneal perfusion, with an i.p. bolus injection. Results: Hyperthermic perfusion with 15 mug/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 mug/ml in 20 ml). The drug concentration in small (1-5mm) intra-peritoneal tumors was also comparable for both these treatments, and for normothermic perfusion. Conclusion: Mild hyperthermic perfusion with cisplatin (40degreeC/90 minutes) did not improve drug uptake in small intra-peritoneal tumors, relative to normothermic perfusion or i.p. bolus injection.