Pharmacokinetics and pharmacodynamics of perioperative cancer chemotherapy in peritoneal surface malignancy

The peritoneal surface remains an important failure site for patients with gastrointestinal and gynecologic malignancies. During the last 2 decades, novel therapeutic approaches, combining cytoreductive surgery with intraoperative intracavitary and intravenous chemotherapy, have emerged for peritoneal carcinomatosis patients. This has resulted in remarkable clinical successes in contrast with prior failures. Although further clinical data from phase II and III trials supporting this combined treatment protocols are necessary, an optimalization of the wide variety of different perioperative cancer chemotherapy protocols used in these treatment regimens is equally important. To this date, a clear understanding of the pharmacology of perioperative chemotherapy is still lacking. The efficacy of intraperitoneal cancer chemotherapy protocols is governed as much by nonpharmacokinetic variables (tumor nodule size, density, vascularity, interstitial fluid pressure, and binding) as by the pharmacokinetic variables (dose, volume, duration, pressure, and carrier solution). Our recent data support the importance of the tumor nodule as the most meaningful pharmacologic end point. Timing of perioperative intravenous chemotherapy may substantially influence the pharmacokinetics. This review aims to clarify the pharmacokinetic and pharmacodynamic data currently available regarding the intraperitoneal delivery of cancer chemotherapy agents in patients with peritoneal carcinomatosis.