ABSTRACT
PURPOSE: To determine the systemic exposure to cisplatin and paclitaxel after adjuvant intraperitoneal administration in patients with advanced ovarian cancer who underwent primary debulking surgery. This could provide an explanation for the high incidence of systemic adverse events associated with this treatment regimen. METHODS: This is a prospective pharmacokinetic study in patients with newly diagnosed advanced ovarian cancer who were treated with intraperitoneal administered cisplatin and paclitaxel. Plasma and peritoneal fluid samples were obtained during the first treatment cycle. The systemic exposure to cisplatin and paclitaxel was determined and compared to previously published exposure data after intravenous administration. An exploratory analysis was performed to investigate the relation between systemic exposure to cisplatin and the occurrence of adverse events. RESULTS: Pharmacokinetics of ultrafiltered cisplatin were studied in eleven evaluable patients. The geometric mean [range] peak plasma concentration (Cmax) and area under the plasma-concentration time curve (AUC0-24 h) for cisplatin was 2.2 [1.8-2.7] mg/L and 10.1 [9.0-12.6] mg h/L, with a coefficient of variation (CV%) of 14 and 13.0%, respectively. The geometric mean [range] observed plasma concentration of paclitaxel was 0.06 [0.04-0.08] mg/L. No correlation was found between systemic exposure to ultrafiltered cisplatin and adverse events. CONCLUSION: Systemic exposure to ultrafiltered cisplatin after intraperitoneal administration is high. In addition to a local effect, this provides a pharmacological explanation for high incidence of adverse events seen after intraperitoneal administration of high-dose cisplatin. The study was registered at ClinicalTrials.gov under registration number NCT02861872.
