A device that sprays aerosolized chemotherapy drugs directly onto peritoneal tumors is now being tested in a Phase I trial in the U.S. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a drug delivery tool that aerosolizes liquid medication and lets the surgeon apply the spray into the abdominal cavity to treat peritoneal carcinomatosis, according to Amit Merchea, MD, a consultant for Colon & Rectal Surgery in the Department of Surgery at the Mayo Clinic, Jacksonville, Fla. He is the first to use the device in a patient in the U.S.
PIPAC was initially developed in 2011 in Germany and used in several European countries as a palliative therapy; however, it's still investigational. Now it is just finding its way into the U.S. via a Phase I trial being conducted as a collaboration between the Mayo Clinic, California's City of Hope Cancer Center, Northwell Health Cancer Institute in New York, and the National Cancer Institute (NCT04329494).
"When I first heard about [PIPAC], it was really exciting. It was revolutionary in the treatment of this disease. These patients often have minimal hope with limited treatment options and very poor outcomes and survival," Merchea noted.
PIPAC is used to treat tumors that have metastasized to the peritoneal space. Because it does not treat primary tumors, it's considered palliative but shows promise in terms of improving or maintaining quality of life. Some studies suggest it may offer modest improvements in survival, depending on the type of cancer.
PIPAC consists of a nebulizer that is connected to a high-pressure injector. The end of the injector is inserted into the abdomen laparoscopically, which includes inflating the abdomen with carbon dioxide (which is done during normal laparoscopy). Chemotherapy is aerosolized into the abdomen allowing the medication to directly reach target cells in the peritoneal space.
The idea is that it delivers a higher concentration of chemotherapy to cancer cells than what systemic chemotherapy can provide, but using less drug overall. It is also less invasive than hyperthermic intraperitoneal chemotherapy (HIPEC), with lower rates of reported morbidity and mortality.
Research Studies
In a systematic review of PIPAC published in Lancet Oncology in 2019, European researchers concluded that PIPAC is feasible and safe, and that it can be considered as a treatment option for refractory, isolated peritoneal metastasis of various origins (doi: https://doi.org/10.1016/S1470-2045(19)30318-3). It also noted that data on objective response and quality of life were encouraging.
The review included studies of PIPAC published between 2011 and 2019, and included a total of 106 articles or reports, and 45 clinical studies on 1,810 PIPAC procedures in 838 patients. The researchers found PIPAC delivery was feasible in 64 percent of patients with few intraoperative and postoperative surgical complications (about 3%).
Adverse events greater than grade 2 occurred after 12-15 percent of procedures, and typically included bowel obstruction, bleeding, and abdominal pain. PIPAC can be repeated in patients and was not found to have a negative effect on quality of life.
They also reported an objective clinical response of 62-88 percent "for patients with ovarian cancer (median survival of 11-14 months), 50-91 percent for gastric cancer (median survival of 8-15 months), 71-86 percent for colorectal cancer (median survival of 16 months), and 67-75 percent (median survival of 27 months) for peritoneal mesothelioma."
A study published in 2018 in Pleura and Peritoneum reported PIPAC can be used as an outpatient procedure (doi: https://doi.org/10.1515/pp-2018-0128). The researchers used data from their prospective PIPAC-OPC2 study. A total of 106 PIPAC procedures were performed in 41 patients with gastrointestinal or ovarian peritoneal metastasis (PM). Patients with PM were treated with cisplatin and doxorubicin, and patients with colorectal PM were treated by oxaliplatin using the device.
Overall, 90 percent of the patients were pretreated with systemic chemotherapy. Twenty-four percent of the first PIPAC procedures were completed in an outpatient setting, which increased to 65 percent for the third procedure. Increasing numbers of cisplatin and doxorubicin cohort underwent PIPAC as outpatients in subsequent treatments, increasing from 28 percent in the first treatment compared to 80 percent for the third, respectively. This contrasted to 11 percent and 20 percent, respectively, in the PIPAC oxaliplatin group.
The researchers reported that there were no readmissions after outpatient care. However, they noted that postoperative morphine administration was more frequent in the PIPAC oxaliplatin group.
Generally, PIPAC might provide an alternative to HIPEC, which requires a large incision through which tumor debulking is done, as well as a hospital stay. While HIPEC has some high-level evidence in its favor, "it is an expensive operation with high morbidity, high mortality, and then you administer the chemotherapy after that," Merchea said.
Another intriguing feature of PIPAC is that it can be repeated in individual patients.
"PIPAC tends to be repeated every 6-8 weeks. We deliver the treatment, patients are on chemotherapy in the interim in many situations, then we go back and we can treat again. And we can also get additional tissue samples to actually measure the real-time response of the treatment. We don't have that opportunity with regular chemotherapy or other modalities or treating this," he said.
However, it's important to know the device is not available in the U.S. and won't have FDA approval until more studies have been completed.
Pippa Wysong is a contributing writer.