Implementation and Evaluation of PIPAC for the Treatment of Patients With Peritoneal Carcinomatosis - a Feasibility Study.

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.

The installation of chemotherapeutic agents within the peritoneal cavity would seem a simple and effective treatment of PC - at least from a theoretical point of view. Unfortunately, the effect of intraperitoneal chemotherapy on PC is disappointing. Like with SC, the poor response rates may be explained by the poor penetration of the active chemical substances into the PC plaques. Combining cytoreductive surgery (CRS) with intraperitoneal chemotherapy has gained interest in the recent years, but this approach can only be used in highly selected patients (where CRS is possible), and the procedure carries a significant risk of complications and side effects. Thus, a minimally invasive and safe delivery of relevant chemotherapy in such concentration that may allow it to work efficiently on the PC plaques would be an ideal platform for a new treatment strategy in these patients.

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 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 intra-abdominal air saturated with chemotherapy is evacuated through a standard trocar.

Recently, a German research group published their preliminary experience with PIPAC in gastric and ovarian cancer patients with PC .

PIPAC is not available freely on the market, and the procedure is not 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.