Role of Intraperitoneal Intraoperative Chemotherapy with Paclitaxel in the Surgical Treatment of Peritoneal Carcinomatosis from Ovarian Cancer. Hyperthermia versus Normothermia. A randomized controlled trial

Abstract

ABSTRACTBackgroundThe treatment of ovarian carcinomatosis with cytoreductive surgery and HIPEC is still controversial. The effect and pharmacokinetics of the chemotherapeutics used (specially taxanes) are under consideration at present.MethodsA phase II, simple blind and randomized controlled trial (NTC02739698) was performed. Thirty-two patients with primary or recurrent ovarian carcinomatosis undergoing cytoreductive surgery (CRS) and intraoperative intraperitoneal chemotherapy with paclitaxel (PTX) were included; 16 in hyperthermic and 16 in normothermic conditions. Tissue, serum and plasma samples were taken in every patient before and after intraperitoneal chemotherapy to measure the concentration of PTX. To analyze the inmunohistochemical profile of p53, p27, p21, ki67, PCNA, caspasa-3 and the pathological response a scale of intensity and percentage of expression and a grouped Miller and Payne system were used, respectively. Perioperative characteristics and morbi-mortality were also analyzed.ResultsMain characteristics of patients, surgical morbidity, haematoxicity and nephrotoxicity were similar in both groups. The concentration of paclitaxel in the tissue was higher than that observed in plasma and serum, although no statistically significant differences were found between the two groups. No statistically significant association regarding pathological response and apoptosis (caspasa-3) between both groups was proved. Intraperitoneal PTX reduced the expression of p53, p27, p21, ki67 and PCNA more in hyperthermia group, but not significantly.ConclusionThe use of intraperitoneal PTX has proven an adequate pharmacokinetics with reduction of cell cycle and proliferation markers globally without finding differences between its administration in hyperthermia versus normothermia conditions.