Introduction
cancers, Ovarian cancer, cancer of the female reproductive system, gynaecological malignancies, deaths, hyperthermia
CANCERS, CATHETER COMPLICATIONS, ADVERSE EVENTS, ADVERSE EVENT, OVARIAN CANCER STAGE IIA, OVARIAN CANCER, EPITHELIAL OVARIAN CANCER, CAVITY, EVENTS
Ovarian cancer is a common type of cancer of the female reproductive system. Globally approximately 295,000 new diagnoses and 185,000 deaths were reported in the year 2018, which reflects a mortality-to-incidence ratio of approximately 0.6 which is the highest of all gynaecological cancers [Although first-line platinum-based chemotherapy is considered standard of care for advanced-stage epithelial ovarian cancer, a major controversy concerns the route of administration which can be intravenous or intraperitoneal. Intraperitoneal administration results in increased drug concentrations and exposure time at the target site, which is considered beneficial for the efficacy of these cytotoxic drugs. Despite the theoretical pharmacological advantage, the evidence for clinical benefit of intraperitoneal administration of chemotherapy after primary debulking surgery from phase III trials is inconclusive. Until now, four pivotal phase III trials have been performed investigating different agents, doses and schedules [Negative consequences of intraperitoneal, mainly cisplatin, administration of chemotherapy are higher incidence of adverse events, catheter complications and higher costs compared to intravenous treatment. Adverse events associated with intraperitoneal administration of platinum-based chemotherapy includes both local and systemic events [Intraperitoneal administration can be performed using different approaches. The first method is intraperitoneal administration using an indwelling catheter. The drug remains in the abdominal cavity after administration from where it will be absorbed. The second approach consists of perfusion of the drug immediately after cytoreductive surgery for several hours after which the chemotherapy is removed from the peritoneal cavity. This approach is often combined with hyperthermia, which is referred to as hyperthermic intraperitoneal chemotherapy (HIPEC). A recent developed intraperitoneal drug delivery technique is pressurized intraperitoneal aerosol chemotherapy (PIPAC) using a nebulizer. It can be expected that these different methods of intraperitoneal administration will impact the pharmacokinetics of the drugs. The majority of pharmacokinetic studies regarding intraperitoneal administration of chemotherapy in patients with gynaecological malignancies involve intraoperative administration. Although extensively studied in the past, the available full text articles in English regarding pharmacokinetics after intraperitoneal administration of cisplatin and paclitaxel using an indwelling catheter are considered sparse [The current study investigated the systemic exposure to both cisplatin and paclitaxel after intraperitoneal administration in patients with ovarian cancer stage III receiving intraperitoneal chemotherapy after primary debulking surgery to provide an explanation for the high incidence of systemic adverse events associated with this treatment regimen. Knowledge about the systemic uptake of drugs administered intraperitoneally can help to find the most optimal intraperitoneal chemotherapy schedule that balance efficacy and safety of the treatment.