ABSTRACT
Epithelial ovarian cancer remains confined to the PC for long periods and is largely sensitive to platinum-based chemotherapy. A pharmacologic rationale for delivering chemotherapy drugs directly into the PC was originally proposed by Dedrick [5]. The central focus of the theory is the ability to expose tumor cells to higher concentrations of cytotoxic or biologic agents than would be possible with systemic delivery with its associated toxicity. The relevant factors include the size and polarity of the active molecule and the pharmacokinetics of the peritoneal-to-systemic passage of the drug. The ideal drug would (1) be cleared slowly from the PC and rapidly from the blood, (2) have preclinical data supporting enhanced activity with direct and prolonged exposure, (3) be nontoxic to peritoneal organs, and (4) not require metabolic conversion to the active form in the liver [5]. The impact of intraperitoneal (IP) cytotoxic therapy on a cancer is determined by the peak concentration within the PC and the duration of drug retention within it. This is ref lected in the PC/plasma area under the concentration-versustime curve expressed in mg h/L (Table 13.2) [6]. Of note is that IP chemotherapy reaches the tumor cells not only by direct perfusion from the peritoneal tumor surface but also, following absorption through the peritoneum, by the systemic circulation [9].
