Treatment of ovarian cancer using intraperitoneal chemotherapy with taxanes: from laboratory bench to bedside

Abstract

The combination of a taxane, paclitaxel or docetaxel, and a platinum compound has become the systemic chemotherapy of choice for primary ovarian cancer and has demonstrated high efficacy. However, ultimately most patients will die from this disease. Hence, there is a need for even more effective systemic chemotherapy or different treatment strategies. Intraperitoneal chemotherapy with taxanes is such an alternative treatment option. Ovarian cancer is theoretically an attractive malignancy for this regional treatment, because the disease remains largely confined to the peritoneal cavity. The choice of taxanes for this kind of chemotherapy is rational, because of its high activity against ovarian cancer cells and expected favourable pharmacokinetics because of limited absorption from the peritoneal cavity due to their large molecular weight and first-pass effect in the liver. In animal model and human pharmacokinetic studies, very high intraperitoneal drug concentrations and exposure and high peritoneal tumour concentrations were achieved, while systemic drug levels were low. The combination of intraperitoneal chemotherapy with hyperthermia enhances the penetration and cytotoxic activity of many drugs. Although data concerning thermal enhancement of taxane cytotoxicity are inconsistent, experimental studies show that at high locoregional concentrations there seems to be such an effect. Recently, feasibility and efficacy of this treatment have evidently been demonstrated in various clinical studies. A large randomized trial revealed improvement of outcome by intraperitoneal instillation chemotherapy with paclitaxel and cisplatin as first-line treatment. Moreover, promising results have been observed after intraoperative hyperthermic intraperitoneal chemotherapy with docetaxel for recurrent disease.