Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Unresectable Peritoneal Metastases. Feasibility, Safety and Efficacy Outcomes

Recently, a novel method for chemotherapy administration inside the abdominal cavity gained wide attention among surgical oncologists dealing with peritoneal surface malignancies. Based on laparoscopy, Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a drug delivery system designed to overcome the known hurdles of intraperitoneal chemotherapy. Preclinical data suggest that the aerosol drug that PIPAC creates and the increased intraabdominal pressure obtained during laparoscopy provide highly effective distribution of cytotoxic compounds into tumor nodules. Several studies have documented the favorable safety profile and promising clinical outcomes of repetitive PIPAC in different types of peritoneal malignancies. The present research assessed the feasibility, safety, and antitumor activity of current PIPAC drug treatment schedules through a systematic review of the literature and two retrospective cohort studies on gastric cancer and pancreatic or biliary tract cancer. In addition, it includes the study protocol of the first phase II trial exploring nabpaclitaxel PIPAC in combination with gemcitabine/nabpaclitaxel systemic chemotherapy. The systematic review of the literature of 668 patients showed an overall pathological response rate of 44% and a severe adverse events rate of 10%. In the single-center cohort of 28 consecutive patients affected by gastric cancer peritoneal metastases undergoing cisplatin/doxorubicin PIPAC and systemic chemotherapy, the pathological response rate, in the Intention-to Treat population, was 29%, with a 7% rate of severe adverse events and 1.7 PIPAC procedures per patient. In the 20 patients cohort of pancreatic and biliary tract cancer PM undergoing oxaliplatin or cisplatin/doxorubicin PIPAC, the pathological response rate was 42% and 62%, respectively. Concerning safety, there was just one intraoperative bowel perforation and no severe postoperative adverse events. PIPAC was feasible and safe, with the pathological response observed suggesting a high antitumoral activity. Despite such encouraging outcomes, the present research, as well as most of the literature, is affected by several biases and the resulting evidence is controversial. More phase I and II trials might be necessary to fill this knowledge gap.