Safety and feasibility of pressurized intraperitoneal aerosol chemotherapy (PIPAC) associated with systemic chemotherapy: an innovative approach to treat peritoneal carcinomatosis

Abstract

Background: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment that applies chemotherapeutic drugs into the peritoneal cavity as an aerosol under pressure. It improves local bioavailability of chemotherapeutic drugs as compared with conventional intraperitoneal chemotherapy. It has been proved to be safe and feasible if performed as an exclusive treatment in patients affected by peritoneal carcinomatosis. The first results in patients treated with PIPAC associated with systemic chemotherapy are presented.

Methods: Between June 2015 and February 2016, 57 PIPAC applications with oxaliplatin or cisplatin + doxorubicin every 6 weeks at 37 °C and 12 mmHg for 30 min were performed. Forty PIPAC procedures performed in 14 patients were included in this study; thirteen patients were undergoing systemic chemotherapy with a wash-out interval of at least 2 weeks before and 1 week after each PIPAC. Safety, tolerability, and postoperative complications were assessed by collection of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) 2.

Results: Forty PIPAC administrations were performed in 14 patients with no major perioperative complications. CTCAE grades 1 and 2 were observed after six and eight procedures, respectively, for abdominal pain and nausea. Renal and hepatic functions were not impaired; no cumulative renal toxicity was observed after repeated PIPAC procedures in association with systemic chemotherapy.

Conclusions: These preliminary data show that the association of PIPAC and systemic chemotherapy does not induce significant hepatic and renal toxicity. It allows inclusion of patients with extraperitoneal disease or at a high risk of developing it. Further studies are needed to assess whether this combination therapy could become part of the standard treatment for peritoneal carcinomatosis.

Keywords: Colorectal cancer; Gastric cancer; Metastasis; Peritoneum; Pneumoperitoneum; Surgery.

Fig. 1

Box plot of liver, renal, and pancreatic functions before the intervention and during the hospital stay. The light blue and blue boxes represent the second and the third quartile, respectively. The upper and lower whiskers represent scores outside the middle 50 %, the highest and lowest value, respectively. The red line represents the upper limit of normal range of measured parameters. PIPAC pressurized intraperitoneal aerosol chemotherapy, CTCAE common terminology criteria for adverse events, PC peritoneal carcinomatosis, CRC colorectal cancer, EOC epithelial ovarian cancer, GC gastric cancer, DMPM diffuse malignant peritoneal mesothelioma, CRS cytoreductive surgery, HIPEC hyperthermic intraperitoneal chemotherapy, IPC intraperitoneal chemotherapy, CT computed tomography, LMWH low molecular weight heparin, PCI Peritoneal Cancer Index, CRP C-reactive protein, POD postoperative day, and QoL quality of life