Clinical trialPhase 3Ovarian cancer

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

N Engl J Med · 2018245 patients

van Driel WJ, Koole SN, Sikorska K, Schagen van Leeuwen JH, Schreuder HWR, Hermans RHM, et al. N Engl J Med. 2018. 378:230-240

A newer report of this study has been published: Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial (2023)

Study type: Clinical trial
Study name: OVHIPEC-1
Phase: Phase 3
Design: Randomised, multicentre, open-label trial
Sample size: 245 patients
Source: N Engl J Med · 2018
Trial registration: NCT00426257

In plain words

HIPEC means washing the inside of the abdomen with a warm solution containing a chemotherapy drug (cisplatin) at the end of surgery. In this study, in patients who had chemotherapy first and then surgery, adding HIPEC helped them live about a year longer on average, without increasing serious side effects. This procedure is done only in specialist centres, and not all guidelines yet consider it standard.

Key results

HR 0.66

Risk of recurrence or death

95% CI 0.50–0.87; P=0.003

14.2 vs 10.7 months

Median recurrence-free survival

45.7 vs 33.9 months

Median overall survival

HR for death 0.67 (95% CI 0.48–0.94); P=0.02; median follow-up 4.7 years

27% vs 25%

Grade 3 or 4 adverse events

P=0.76

Drugs in this study:Carboplatin (Paraplatin)Cisplatin (Platinol)Paclitaxel (Taxol)

Dose and schedule cards

HIPEC with cisplatin at interval debulking surgery (OVHIPEC-1)

Stage III with at least stable disease after 3 cycles of neoadjuvant chemotherapy, when complete or optimal cytoreduction (residual disease 10 mm or less) is feasibleOn the page “Ovarian cancer” · First line: chemotherapy and surgery

Stage III with at least stable disease after 3 cycles of neoadjuvant chemotherapy, when complete or optimal cytoreduction (residual disease 10 mm or less) is feasible

Drug	Dose	Route	Schedule
Before surgery: 3 cycles
Carboplatin + paclitaxel	AUC 5–6 + 175 mg/m²	IV	Day 1 every 21 days
During interval debulking surgery
Cisplatin (HIPEC)	100 mg/m²	Intraperitoneal, hyperthermic	Once
After surgery: 3 cycles
Carboplatin + paclitaxel	AUC 5–6 + 175 mg/m²	IV	Day 1 every 21 days

Cycle length: Every 21 days (IV chemotherapy)
Duration: 6 cycles in total

Grade 3–4 adverse events were similar in the two groups (27% vs 25%). The Pan-Asian ESMO guideline does not consider HIPEC a first-line standard [II, D]; only at experienced centres.

On the page “Ovarian cancer” · First line: chemotherapy and surgery

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Interval surgery + HIPEC (122 patients)

Neoadjuvant chemotherapy: three cycles of carboplatin (AUC 5 to 6 mg/mL per minute) and paclitaxel (175 mg/m²); then interval cytoreductive surgery with HIPEC using cisplatin 100 mg/m²; then three further cycles of carboplatin and paclitaxel after surgery.

2Interval surgery without HIPEC (123 patients)

The same neoadjuvant and postoperative chemotherapy, without HIPEC.

Source of the regimen details: Abstract of the paper (carboplatin AUC 5–6, paclitaxel 175 mg/m², HIPEC cisplatin 100 mg/m²)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with stage III epithelial ovarian cancer who had at least stable disease after three cycles of neoadjuvant chemotherapy and in whom complete or optimal cytoreductive surgery (residual disease 10 mm or less) was feasible; randomisation during surgery.

Endpoints

Primary endpoint: recurrence-free survival. Key secondary: overall survival and adverse event profile.

Safety and side effects

The proportion of patients with grade 3 or 4 adverse events was similar in the two groups (27% with HIPEC and 25% without; P=0.76).

Clinical significance and place in guidelines

OVHIPEC-1 was the first randomised phase 3 trial to show an overall survival benefit of HIPEC at interval surgery for ovarian cancer. However, because the evidence is debated, the ESMO guideline (Pan-Asian adapted version 2025) does not consider HIPEC [II, D] or intraperitoneal chemotherapy [I, E] standard first-line treatment. The OVHIPEC-2 trial (primary surgery) is ongoing.

Limitations

Open-label design and relatively small sample size; no blinding; only patients receiving neoadjuvant chemotherapy (interval surgery) were studied; conducted before the era of PARP inhibitors.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.