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Surgery after platinum-based chemotherapy and the addition of HIPEC
Source: Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: May 14, 2025 · Captured 2026-09-09.
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Hyperthermic intraperitoneal chemotherapy (HIPEC) is another pharmacological-based modality to enhance the antitumor effects via direct drug delivery to peritoneal surfaces. It was initially tested against mucinous tumors of gastrointestinal origin.[48] Increasingly, HIPEC is being applied to ovarian cancers. There is considerable variation in patient selection, drugs administered, and time at target temperatures (most often 30 minutes at 42°C). The role of HIPEC remains experimental in the treatment of patients with high-grade serous ovarian cancers.
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Experience with HIPEC spans more than two decades after initial publications that have since been summarized.[49] Evidence for its use in ovarian cancer includes a randomized study.
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Evidence (surgery after platinum-based chemotherapy and the addition of HIPEC):
The final results of a phase III, open-label, Dutch study (NCT00426257) have been published. The study was performed in eight hospitals and included 245 patients with newly diagnosed ovarian cancer who were at least stable after receiving three cycles of carboplatin (AUC, 5–6) and paclitaxel (175 mg/m2), both of which were given by IV every 3 weeks.[50] Randomization took place at the time of surgery, and patients were assigned to undergo either cytoreductive surgery without HIPEC (n = 123) or with HIPEC (n = 122). HIPEC consisted of perfusion of the abdominal cavity with cisplatin (100 mg/m2) in heated saline at 40°C (104°F) that was maintained for 60 minutes. Sodium thiosulfate was given at the start of the perfusion as an IV bolus (9 g/m2 in 200 mL) followed by continuous infusion IV (12 g/m2 in 1L) for 6 hours.[51] All patients subsequently received three additional cycles of IV chemotherapy. Only two patients received first-line PARP inhibitors for maintenance. The final survival analysis was reported with a median follow-up of 10 years.[52]
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The final results of a phase III, open-label, Dutch study (NCT00426257) have been published. The study was performed in eight hospitals and included 245 patients with newly diagnosed ovarian cancer who were at least stable after receiving three cycles of carboplatin (AUC, 5–6) and paclitaxel (175 mg/m2), both of which were given by IV every 3 weeks.[50] Randomization took place at the time of surgery, and patients were assigned to undergo either cytoreductive surgery without HIPEC (n = 123) or with HIPEC (n = 122). HIPEC consisted of perfusion of the abdominal cavity with cisplatin (100 mg/m2) in heated saline at 40°C (104°F) that was maintained for 60 minutes. Sodium thiosulfate was given at the start of the perfusion as an IV bolus (9 g/m2 in 200 mL) followed by continuous infusion IV (12 g/m2 in 1L) for 6 hours.[51] All patients subsequently received three additional cycles of IV chemotherapy. Only two patients received first-line PARP inhibitors for maintenance. The final survival analysis was reported with a median follow-up of 10 years.[52]
The median OS was 33.3 months for patients in the surgery-alone group and 44.9 months for patients in the HIPEC group (HR, 0.70; 95% CI, 0.53–0.92).[51][Level of evidence A1]
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The final results of a phase III, open-label, Dutch study (NCT00426257) have been published. The study was performed in eight hospitals and included 245 patients with newly diagnosed ovarian cancer who were at least stable after receiving three cycles of carboplatin (AUC, 5–6) and paclitaxel (175 mg/m2), both of which were given by IV every 3 weeks.[50] Randomization took place at the time of surgery, and patients were assigned to undergo either cytoreductive surgery without HIPEC (n = 123) or with HIPEC (n = 122). HIPEC consisted of perfusion of the abdominal cavity with cisplatin (100 mg/m2) in heated saline at 40°C (104°F) that was maintained for 60 minutes. Sodium thiosulfate was given at the start of the perfusion as an IV bolus (9 g/m2 in 200 mL) followed by continuous infusion IV (12 g/m2 in 1L) for 6 hours.[51] All patients subsequently received three additional cycles of IV chemotherapy. Only two patients received first-line PARP inhibitors for maintenance. The final survival analysis was reported with a median follow-up of 10 years.[52]
The median recurrence-free survival was 10.7 months for patients in the surgery-alone group and 14.3 months for patients in the HIPEC group (HR, 0.63; 95% CI, 0.48–0.83).
The final results of a phase III, open-label, Dutch study (NCT00426257) have been published. The study was performed in eight hospitals and included 245 patients with newly diagnosed ovarian cancer who were at least stable after receiving three cycles of carboplatin (AUC, 5–6) and paclitaxel (175 mg/m2), both of which were given by IV every 3 weeks.[50] Randomization took place at the time of surgery, and patients were assigned to undergo either cytoreductive surgery without HIPEC (n = 123) or with HIPEC (n = 122). HIPEC consisted of perfusion of the abdominal cavity with cisplatin (100 mg/m2) in heated saline at 40°C (104°F) that was maintained for 60 minutes. Sodium thiosulfate was given at the start of the perfusion as an IV bolus (9 g/m2 in 200 mL) followed by continuous infusion IV (12 g/m2 in 1L) for 6 hours.[51] All patients subsequently received three additional cycles of IV chemotherapy. Only two patients received first-line PARP inhibitors for maintenance. The final survival analysis was reported with a median follow-up of 10 years.[52]
An exploratory analysis suggested patients without germline or somatic BRCA pathogenic variants had a better disease response to HIPEC. The effect was most pronounced for patients with BRCA wild-type tumors who were found to be homologous recombination deficient (HR, 0.41; 95% CI, 0.20–0.85).
In institutions that have experience performing HIPEC, adverse events were comparable between women who did and did not receive HIPEC during interval debulking surgery. Patients in the HIPEC group had higher incidences of ileus (3% vs. 8%), fever (8% vs. 12%), and thromboembolic events (2% vs. 6%), but the rates of electrolyte changes (5% vs. 6%) and neuropathy (27% vs. 31%) were similar between the HIPEC and the surgery-only groups. The use of sodium thiosulfate was mandatory as part of HIPEC protocol in a published phase I trial.[53] HIPEC should be considered an option during interval debulking surgery for patients who have access to a surgical team who has experience performing HIPEC and in whom optimal resection of disease is achieved at the time of interval debulking surgery.
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