Hyperthermic intraperitoneal chemotherapy boosts advanced ovarian cancer outcomes
medwireNews: Women with advanced-stage ovarian cancer derive a significant survival benefit from the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery, phase III trial results indicate.
Lead researcher Willemien van Driel, from the Netherlands Cancer Institute in Amsterdam, and colleagues explain that “[i]ntraperitoneal delivery of chemotherapy enhances drug delivery at the peritoneal surface,” with hyperthermic conditions not only increasing drug penetration but also boosting the sensitivity of the cancer to chemotherapy by impairing DNA repair mechanisms.
They recruited 245 women with stage III epithelial ovarian, fallopian tube, or peritoneal cancer that was too extensive for primary cytoreductive surgery. Participants had achieved at least stable disease after three cycles of carboplatin plus paclitaxel and were expected to have complete or optimal cytoreduction, defined as no visible disease or one or more residual tumors no larger than 10 mm in diameter, respectively. They were randomly assigned to undergo surgery either with or without a single administration of HIPEC with cisplatin 100 mg/m2, after which all patients received a further three cycles of carboplatin and paclitaxel.
As reported in The New England Journal of Medicine, patients who received cytoreductive surgery with HIPEC had a significant 34% reduced risk for disease recurrence, progression, or death, with a median recurrence-free survival time of 14.2 months versus 10.7 months for the surgery-only group.
The HIPEC group also had a significant 33% reduced risk for death, and longer overall survival than the control group, at a median of 45.7 and 33.9 months, respectively.
an absence of well-designed clinical trials has rendered the field of HIPEC to an esoteric realm... Until now.
The study authors note that the addition of HIPEC improved outcomes with “little effect on safety.” The rate of adverse events of grade 3 or 4 was comparable for the HIPEC and control arms, at a respective 27% and 25%. And there were no delays in the re-initiation of chemotherapy postoperatively, and a comparable proportion of participants in both arms completed all three cycles.
Furthermore, there were no significant differences between patients who did and did not receive HIPEC with regard to health-related quality of life outcomes, which were assessed using a variety of tools.
Writing in a linked editorial, David Spriggs and Oliver Zivanovic (both from Memorial Sloan Kettering Cancer Center, New York, USA) say that these findings “represent the most convincing information to date that a single administration of [HIPEC] delivered at the end of a surgical resection of ovarian cancer may provide a meaningful advantage for a defined group of patients with cancer.”
They believe, however, that the trial “should not drive changes in practice yet.”
Some unanswered questions – such as the cost of the intervention and the patient groups most likely to derive a benefit – need to be addressed before HIPEC can be incorporated in routine practice, say the editorialists.
“These considerations will be important for clinical trial investigators as they focus on the positive effect of HIPEC as an intervention as compared with the effects of promising new agent combinations or immunotherapy treatments,” they conclude.
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