Hyperthermia During Intraperitoneal Chemotherapy With Paclitaxel or Docetaxel for Ovarian Cancer: Is There Any Benefit?

Pharmacological considerations regarding intraoperative hyperthermic intraperitoneal chemotherapy for ovarian cancer

“…Recently, however, some studies demonstrated that hyperthermia may have some adverse oncological effects [41]. Hyperthermia may initiate immunosuppressive effects and consequently disease progression [42], whereas the heat shock proteins that are systemically released in high concentrations in patients undergoing HIPEC may impair the efficacy of hyperthermia and chemotherapy [43][44][45][46][47] as well as result in decreased apoptosis and increased tumour cell proliferation, invasiveness and metastatic dissemination [46,48].…”

“…The use of paclitaxel for HIPEC may not be appropriate because thermal enhancement seems to be limited, or even absent, in experimental studies [28,41,71]. Therefore, paclitaxel could be administered for normothermic intraoperative intraperitoneal chemotherapy, exploiting its wellknown great effectiveness against ovarian cancer, proved in systemic chemotherapy and experimental studies, as well as its highly favourable profile reported in pharmacokinetic studies, while avoiding the potential oncological adverse effects and morbidity of additional hyperthermia [41]. Results of a small randomized trial (NCT02739698) comparing hyperthermic with normothermic intraoperative intraperitoneal chemotherapy with paclitaxel after CRS for ovarian cancer are eagerly awaited [76].…”

“…Docetaxel, another taxane which is also highly effective in the systemic chemotherapy of ovarian cancer, has been less often administered in intraperitoneal chemotherapy. Docetaxel may even be more effective in intraperitoneal chemotherapy, since in our recent experimental study with drug concentrations mimicking those of intraperitoneal chemotherapy, docetaxel was more cytotoxic than paclitaxel [41]. Pharmacokinetic studies demonstrated for docetaxel a promising profile comparable to that of paclitaxel, with a peritoneal to plasma AUC ratio of 150-3000 [6,7,71,72,80].…”

“…Pharmacokinetic studies demonstrated for docetaxel a promising profile comparable to that of paclitaxel, with a peritoneal to plasma AUC ratio of 150-3000 [6,7,71,72,80]. Similar to paclitaxel, thermal enhancement is limited or absent for docetaxel, while the depth of tumour penetration is appraised to be 1.5 mm [28,41,72,72]. With the most common dose of 75-125 mg/m 2 , its toxicity profile is generally well tolerated.…”

Novel Gellan Gum-Based In Situ Nanovesicle Formulation of Docetaxel for Its Localized Delivery Using Depot Formation

“…Docetaxel (DTX), as an armamentarium has been successfully engaged in tackling ovarian carcinoma (1). Unfortunately, commercial DTX injectable formulation leads to RBC hemolysis, neuropathy along with spleen and kidney injury (2,3).…”