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

Anticancer Res. 2020 Dec;40(12):6769-6780. doi: 10.21873/anticanres.14700. Epub 2020 Dec 7.

Abstract

Background/aim: Intraperitoneal chemotherapy with taxanes provides high locoregional drug concentrations. Regarding their synergy with hyperthermia, results have been inconclusive. In this in vitro study, the thermal enhancement of the effect of paclitaxel and docetaxel on ovarian cancer cells under conditions mimicking those during hyperthermic intraperitoneal chemotherapy (HIPEC) is evaluated.

Materials and methods: Cisplatin-resistant SKOV-3 and OVCAR-3 ovarian cancer cells were exposed for 2 h to 0.1, 1 and 3 μΜ of paclitaxel and docetaxel at 37°C (normothermia) and 41.5°C (hyperthermia). Cell proliferation and cell-cycle distribution were evaluated after 24 h, 3 days and 7 days.

Results: A concentration-dependent cytotoxic effect on cell proliferation was observed. Concurrent hyperthermia caused an increased arrest of cells in the G2/M phase. At 7 days, thermal enhancement of drug effect was shown only for treatment of OVCAR-3 cells with 1 μM paclitaxel.

Conclusion: The concentration-dependent cytotoxic effect of paclitaxel and docetaxel supports their intraperitoneal use. Due to the lack of or only minimal thermal enhancement, normothermic may be as effective as hyperthermic intraoperative intraperitoneal chemotherapy with taxanes, avoiding, however, potential oncological and treatment-related adverse effects of concurrent hyperthermia.

Keywords: HIPEC; Paclitaxel; docetaxel; hyperthermia; in vitro study; intraperitoneal chemotherapy; ovarian cancer.

MeSH terms

  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Combined Modality Therapy
  • Docetaxel / administration & dosage*
  • Docetaxel / therapeutic use*
  • Female
  • G2 Phase / drug effects
  • Humans
  • Hyperthermia, Induced*
  • Injections, Intraperitoneal
  • Mitosis / drug effects
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy*
  • Paclitaxel / administration & dosage*
  • Paclitaxel / therapeutic use*

Substances

  • Docetaxel
  • Paclitaxel