The addition of hyperthermic intraperitoneal chemotherapy to interval cytoreductive surgery prolonged recurrence-free survival (RFS) and overall survival (OS) without increasing toxicity among patients with stage III epithelial ovarian cancer, according to randomized open-label phase 3 study results published in The New England Journal of Medicine.

“Hyperthermia increases the penetration of chemotherapy at the peritoneal surface and increases the sensitivity of cancer to chemotherapy by impairing DNA repair,” said Willemien J. van Driel,  of the department of gynecology at Netherlands Cancer Institute.

“Hyperthermia also induces apoptosis and activates heat-shock proteins that serve as receptors for natural killer cells, inhibits angiogenesis and has a direct cytotoxic effect by promoting the denaturation of proteins,” van Driel added.

van Driel and colleagues evaluated whether the addition of hyperthermic intraperitoneal chemotherapy to interval cytoreductive surgery would improve outcomes among 245 patients receiving neoadjuvant chemotherapy for stage III epithelial ovarian cancer.

All patients had at least stable disease after three cycles of carboplatin and paclitaxel. At the time of surgery, researchers randomly assigned patients to undergo interval cytoreductive surgery with (n = 122) or without (n = 123) hyperthermic intraperitoneal chemotherapy with 100 mg/m2 cisplatin. Patients underwent three additional cycles of carboplatin and paclitaxel postoperatively.

In the intent-to-treat analysis, disease recurrence or death occurred among 99 patients who underwent hyperthermic intraperitoneal chemotherapy and 110 patients who did not (HR = 0.66; 95% CI, 0.5-0.87). Patients who underwent hyperthermic intraperitoneal chemotherapy also showed longer median RFS (14.2 months vs. 10.7 months) and OS (45.7 months vs. 33.9 months).

Sixty-one patients in the hyperthermic intraperitoneal chemotherapy group died, compared with 76 patients in the surgery-alone group (HR = 0.67; 95% CI, 0.48-0.94). Among patients who underwent bowel resection significantly more of those who received hyperthermic intraperitoneal chemotherapy underwent colostomy or ileostomy (72% vs. 43%; P = .04).

“In the current trial, we evaluated hyperthermic intraperitoneal chemotherapy as a single administration of intraperitoneal chemotherapy during surgery to overcome the side effects and inconvenience of serial adjuvant intraperitoneal chemotherapy and to improve the distribution of heated chemotherapy in the abdominal cavity,” authors noted.

“The authors enrolled only patients who underwent interval cytoreductive surgery after receiving three cycles of neoadjuvant chemotherapy for the primary treatment of ovarian cancer,” they wrote.

“Well-designed clinical trials may eventually identify other subgroups of patients with ovarian cancer who are undergoing therapeutic interventions that differ from those of the population eligible for this trial and might benefit from intraoperative administration of hyperthermic intraperitoneal chemotherapy, but the results of the current trial cannot yet be extrapolated to any other conditions or clinical settings,” they added.