Hyperthermic Intraperitoneal Chemotherapy With Primary or Interval Cytoreductive Surgery for Advanced Ovarian Cancer

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In a Korean study reported in JAMA Surgery, Lim et al found that hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery did not improve progression-free survival vs no HIPEC in women with newly diagnosed stage III or IV epithelial ovarian cancer. A benefit of HIPEC was observed in the subgroup of patients who received interval cytoreductive surgery following neoadjuvant chemotherapy.

Study Details

In the single-blind trial, 184 women from two Korean centers (National Cancer Center and Ajou University Hospital) were randomly assigned between March 2010 and January 2016 to receive cytoreductive surgery with (n = 92) or without (control group, n = 92) HIPEC. Intraoperative HIPEC consisted of 75 mg/m2 of cisplatin perfused through a closed technique with a target temperature of 41.5°C for 90 minutes.

A total of 58 patients in the HIPEC group and 49 in the control group underwent primary cytoreductive surgery. A total of 34 patients in the HIPEC group and 43 in the control group underwent interval cytoreductive surgery after receiving neoadjuvant chemotherapy with three cycles of carboplatin at area under the curve = 5 and paclitaxel at 175 mg/m2. All patients were to receive adjuvant chemotherapy with six cycles of paclitaxel and carboplatin. The primary endpoint was progression-free survival.  

Key Findings

Date of last follow-up was in January 2020, and data were locked in February 2020. Median follow-up was 69.4 months (interquartile range [IQR] = 54.4–86.3 months).

Median progression-free survival was 19.8 months (IQR = 13.7–55.4 months) in the HIPEC group vs 18.8 months (IQR = 13.0–43.2 months) in the control group (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.63–1.21, P = .43). Median overall survival was 69.5 months (IQR = 45.6 months–not reported) in the HIPEC group vs 61.3 months (IQR = 34.3 months–not reported) in the control group (HR = 0.87, 95% CI = 0.58–1.32, P = .52).  

Among patients receiving interval cytoreductive surgery after neoadjuvant chemotherapy, median progression-free survival was 17.4 months (IQR = 13.8–31.5 months) in the HIPEC group vs 15.4 months (IQR = 10.6–21.1 months) in the control group (HR = 0.60, 95% CI = 0.37–0.99, P = .04). Median overall survival was 61.8 months (IQR = 46.7 months–not reported) vs 48.2 months (IQR = 33.8–61.3 months; HR = 0.53, 95% CI = 0.29–0.96, P = .04).

Among patients undergoing primary cytoreductive surgery, median progression-free survival was 23.9 months (IQR = 12.3–71.5 months) in the HIPEC group vs 29.7 months (IQR = 17.2–90.1 months) in the control group (HR = 1.16, 95% CI = 0.74–1.83, P = .51). Median overall survival was 71.3 months (IQR = 45.6 months–not reported) vs not reached (HR = 1.38, 95% CI = 0.75–2.54, P = .29).

Any-grade increased prothrombin time (81.5% vs 65.2%, P = .01) and acute kidney injury (20.7% vs 6.5%, P = .005) were more common in the HIPEC group, as was grade 3 or 4 electrolyte disturbance (80.4% vs 44.6%, P < .001).

The investigators concluded, “The addition of HIPEC to cytoreductive surgery did not improve progression-free and overall survival in patients with advanced epithelial ovarian cancer. Although the results are from a subgroup analysis, the addition of HIPEC to interval cytoreductive surgery provided an improvement of progression-free and overall survival.”

Sang-Yoon Park, MD, PhD, of the Center for Gynecologic Cancer, National Cancer Center, Goyang, is the corresponding author for the JAMA Surgery article.  

Disclosure: The study was supported by grants from the National Cancer Center of Korea. For full disclosures of the study authors, visit

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