Early U.S. Trial Tests PIPAC for Recurrent Ovarian Cancer
- 6 hours ago
- 4 min read
Nakamura B, Senguttuvan R, Ruel NH, et al. Safety and efficacy of cisplatin and doxorubicin pressurized intraperitoneal aerosolized chemotherapy (PIPAC) in patients with ovarian cancer with peritoneal metastases: a multicenter US phase I trial. Ann Surg Oncol. 2026;33:415–425. doi:10.1245/s10434-025-18432-0
When ovarian cancer returns and spreads throughout the abdominal cavity, treatment options can become limited—particularly when the disease cannot be removed surgically or has stopped responding to standard chemotherapy.
A small U.S. phase I trial examined whether pressurized intraperitoneal aerosolized chemotherapy, known as PIPAC, could be delivered safely to patients with recurrent ovarian cancer and peritoneal metastases.
What Is PIPAC?
PIPAC delivers chemotherapy directly into the abdominal cavity as a pressurized mist during a minimally invasive laparoscopic procedure. The pressure and aerosolized delivery are intended to distribute chemotherapy across the peritoneal surfaces and help the medication penetrate tumor tissue.
Unlike HIPEC, which is generally administered once during cytoreductive surgery, PIPAC can be repeated without removing tumors during the procedure. PIPAC remains investigational and is not a standard treatment for ovarian cancer in the United States.
The Key Study Question
Could PIPAC using cisplatin and doxorubicin be delivered safely to patients with heavily pretreated recurrent ovarian cancer, and were there early indications that it could help control disease within the abdomen?
The Big Picture
This prospective phase I trial enrolled 15 women at three U.S. academic medical centers. All participants:
Had ovarian cancer with peritoneal metastases
Had experienced progression after at least one established chemotherapy regimen
Were not candidates for cytoreductive surgery and HIPEC
Had previously undergone primary or interval cytoreductive surgery
Participants had received a median of three previous treatment regimens, with some having received as many as ten. Most patients also had cancer outside the abdominal cavity.
PIPAC with cisplatin and doxorubicin was administered every four to six weeks, with three treatments initially planned. Patients experiencing a benefit could receive as many as six treatments.
What the Researchers Found
PIPAC was successfully delivered
Thirteen of the 15 participants completed at least two PIPAC procedures. Researchers reported no technical failures and no serious surgical complications associated with the laparoscopic procedures.
Serious side effects were uncommon
No dose-limiting toxicities or grade 4 or 5 adverse events were reported. Two grade 3 side effects occurred: abdominal pain in one patient and loss of appetite in another.
The most commonly reported treatment-related side effects were abdominal pain, fatigue and nausea.
Some disease control occurred inside the abdomen
On CT imaging:
One patient experienced a partial response
Four patients had stable disease
Eight experienced disease progression
Among the 13 patients who completed at least two treatments, approximately 31% showed a reduction in their Peritoneal Cancer Index, a surgical measure of tumor burden within the abdomen. Tissue samples showed evidence of tumor response in approximately 46%.
Fluid buildup in the abdomen, known as ascites, remained stable or decreased in 12 of the 13 evaluable patients between the first and second procedures.
One patient with low-grade serous ovarian cancer received six PIPAC cycles and experienced a partial response lasting 14 months. However, other patients with the same subtype had stable or progressive disease, so the study could not identify a specific subtype most likely to benefit.
Overall cancer control remained limited
Median progression-free survival—the length of time before the cancer worsened—was 2.3 months. Median overall survival was 17.1 months, although the small study size and additional treatments received after PIPAC make this number difficult to interpret.
Because PIPAC delivers treatment locally within the abdomen, it did not adequately control cancer elsewhere in the body. Most patients with disease outside the abdominal cavity experienced progression in those areas.
Why This Matters for Patients
This early trial suggests that PIPAC with cisplatin and doxorubicin can be delivered safely and consistently at experienced U.S. centers. It also showed that the medication reached both normal and tumor tissue while producing lower blood concentrations than have historically been reported with intravenous chemotherapy.
However, PIPAC alone provided limited overall disease control in this heavily pretreated population. The researchers suggested that future studies explore PIPAC alongside intravenous therapy so that treatment can address cancer both inside and outside the abdominal cavity.
Researchers must also determine which medications work best when delivered through PIPAC and which patients are most likely to benefit.
Important Study Limitations
This was a phase I trial designed primarily to evaluate safety and feasibility—not to prove that PIPAC improves survival.
The study included only 15 patients, did not have a comparison group and had a relatively short follow-up period. Most participants had received several previous treatments and had cancer outside the abdomen, which may have contributed to the limited disease control.
Quality-of-life data were also incomplete, with only seven patients completing the questionnaires.
The Bottom Line
PIPAC with cisplatin and doxorubicin was feasible and generally well tolerated in this small U.S. trial of women with heavily pretreated recurrent ovarian cancer. Some patients experienced disease stability or signs of response within the abdomen, but most ultimately experienced progression, particularly at disease sites outside the abdominal cavity.
The results support continued research into better PIPAC drug combinations, careful patient selection and treatment approaches that combine PIPAC with systemic therapy. For now, PIPAC should be considered an investigational option available through specialized centers and clinical trials.
