Short summary

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a new treatment option in patients with peritoneal carcinomatosis (PC). PIPAC has proven efficacious in the treatment of PC from ovarian-, colon- and gastric cancer. PIPAC has a favourable profile regarding safety for patients and occupational health aspects. This study evaluates PIPAC in a cohort of Danish patients with PC.

Rationale

Background

Peritoneal carcinomatosis (PC) represents end stage disease in many types of cancer (e.g. gastric, pancreatic, liver, colo-rectal, ovarian) and the majority of patients with PC will die from their disease within 6 months. Platinum-based systemic chemotherapy (SC) may prolong survival in selected patients, but poor performance status and low response rates have led to conservative (nihilistic) treatment strategies in these patients. However, patients with PC who are in good condition and with a remaining life expectancy of more than a few months, may still have an unmet need for additional treatment in order to be able to perform with a high quality of life for as long as possible. These patients often have tried several lines of SC with disappointing results, and alternative and more effective treatment strategies are desperately needed.

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)

Temperature and pressure are important factors during absorption of fluid from the peritoneal cavity, and the use of a relative low intraperitoneal pressure (2-6 mmHg) seems to increase the inflow of intraperitoneal fluid into the abdominal wall. Studies have confirmed that higher tissue concentrations of chemotherapy may be obtained by increasing the intraperitoneal pressure. After years of extensive testing, and the development of a CE-certified micro-pump for safe aerosol infusion, a German research group has designed a system that allows a laparoscopy controlled, intraperitoneal aerosol infusion of chemotherapy (doxorubicin and cisplatin). The aerosol technique ensures that the entire peritoneal surface is covered by chemotherapy, and this is relevant in patients with PC. With the micro-pump positioned through a standard trocar pointing away from the bowels, a commercially available injection pump provides the necessary pressure to induce an aerosol mist covering the peritoneal cavity. After five minutes, the chemotherapy has been delivered, and the injector is turned off. After an additional 25 minutes of simple diffusion, the intraabdominal air saturated with chemotherapy is evacuated through a standard trocar.

The first results are suggesting a significant efficacy of PIPAC in platinum-resistant peritoneal carcinomatosis, which would be a novel treatment option in this dismal situation. Moreover, safety data are good, with a low adverse events profile. This could indicate progress in a palliative situation, where systemic combination chemotherapy is poorly tolerated by patients.

PIPAC is not available freely on the market, and the procedure is not EMA/FDA approved yet. The German research team has emphasized, that despite the very encouraging results obtained so far, the efficacy and safety of PIPAC still has to be assessed in adequate clinical trials. Therefore, during the visit to Herne a formal scientific cooperation between the Department of Surgical Oncology and Therapy Center for Peritoneal Cancer (Marien Hospital, Ruhr-University Bochum) and the Department of Surgery and Department of Oncology (Odense University Hospital) was established.

Aim

In a compassionate use program, the aim of this study is to implement and evaluate the PIPAC procedure at Odense University Hospital under strict observation of both patient and occupational health safety aspects. Thus, it is important to emphasize, that the primary aim of this feasibility study is a quick and safe implementation of a new combined surgical-oncologic treatment technique which uses conventional chemotherapy in a new way in desperately ill cancer patients. For technical and safety reasons this implementation needs to be fulfilled and documented before patients can be enrolled in clinical trials.

Description of the cohort

The cohort comprises patients with histological or cytological verified malignancy. The patients must be over 18 years of age and have clinical or radiological evidence of peritoneal carcinomatosis without indication for treatment with standard chemotherapy. The patients must be in general good physical condition (performance status 0-2) and have life expectancy of more than 3 months.

Data and biological material

• Quadrant biopsies of the peritoneum.
• EORTC Quality of Life schemes.
• Patient history including date of diagnosis and earlier chemotherapy treatment.
• Perioperative data including amount of chemotherapy, procedure time, PONV, pain scores etc. 

Collaborating researchers and departments

Department of Surgery, Odense University Hospital

• PhD-student and Investigator Martin Graversen, MD
• Professor and Sponsor Michael Bau Mortensen

Department of Surgical Oncology and Therapy Center for Peritoneal Cancer, Marien Hospital, Ruhr-University Bochum, Germany

• Professor and Director Marc A. Reymond

Department of Gynaecology and Obstetrics, Odense University Hospital

• Professor Ole Mogensen

Department of Oncology, Odense University Hospital

• Professor Per Pfeiffer, Professor Jørn Herrstedt

Department of Clinical Pathology, Odense University Hospital

• Consulting pathologist Sönke Detlefsen, PhD