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Grand Rounds

Is Hyperthermic Intraperitoneal Chemotherapy the Next Step Forward in the Treatment of Ovarian Cancer?

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BACKGROUND AND PURPOSE:

  • The most effective treatment for ovarian cancer, often diagnosed at advanced stage, is surgery followed by 6 cycles of chemotherapy
    • Another option is surgical cytoreduction after 3 cycles of chemotherapy
  • There may be benefit to hyperthermic intraperitoneal chemotherapy (HIPEC) delivered during surgery
    • Hyperthermia causes apoptosis and direct cytotoxic effects aside from other positive cancer treatment attributes
  • Willamien et al. (NEJM, 2018) studied whether the addition of HIPEC to interval cytoreductive surgery would improve outcomes in women with stage III epithelial ovarian cancer

METHODS:

  • Randomized Multicenter, open-label, phase 3 controlled trial
  • Participants
    • Patients with least stable disease after three cycles chemotherapy
    • Unfavorable prognostic stage III ovarian cancer
      • ineligible for primary cytoreduction because of extensive abdominal disease
    • Patients were randomized to the following groups
      • Interval cytoreductive surgery with HIPEC with cisplatin (100 mg per square meter)
      • Interval cytoreductive surgery without HIPEC
    • Three additional cycles of carboplatin and paclitaxel were administered postoperatively
    • Primary end point
      • Recurrence-free survival
    • Secondary end points:
      • Overall survival | Side-effect profile

RESULTS:

  • 245 patients were included in the study
  • There were significantly higher rates of disease recurrence or death in the non-HIPEC group (89%) compared to the HIPEC group (81%)
    • Hazard ratio for disease recurrence or death, 0.66; 95% CI, 0.50 to 0.87 (P=0.003)
  • Median recurrence-free survival was 10.7 months in the non-HIPEC group vs 14.2 months in the HIPEC group
  • At a median follow-up of 4.7 years significantly fewer patients in HIPEC group had died (62%), compared to non-HIPEC (50%)
    • Hazard ratio, 0.67; 95% CI, 0.48 to 0.94 (P=0.02)
  • Median overall survival was 33.9 months in the non-HIPEC group and 45.7 months in the HIPEC group
  • Adverse events of grade 3 or 4 was similar in the non-HIPEC group (25%) and HIPEC group (27%); (P=0.76)

CONCLUSION:

  • This efficacy data suggests that adding HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival in women with stage III epithelial ovarian cancer
  • HIPEC group median overall survival was 12 months longer and median recurrence-free survival was 3.5 months longer
  • Authors conclude that “HIPEC plus complete or optimal interval cytoreductive surgery resulted in longer survival than cytoreductive surgery alone”

Learn More – Primary Sources:

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

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USPSTF Releases Final Recommendation On Ovarian Cancer Screening
Ovarian or Endometrial Cancer? Consider Lynch Syndrome
Screening for Ovarian Cancer – Fantasy or Reality?
BRCA1 & BRCA2 Mutations: What Are the Risks for Developing Breast and Ovarian Cancer?

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