Abstract
Background: Peritoneal carcinomatosis is a common metastatic pattern in ovarian, gastric, colorectal, and appendiceal cancer; systemic chemotherapy is the current standard of care for peritoneal metastatic disease; however, in a subset of patients its beneficial effect remains questionable. More effective perioperative chemotherapy is needed. Materials and methods: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment that applies chemotherapeutic drugs into the peritoneal cavity as an aerosol under pressure. It’s a safe and feasible approach that improves local bioavailability of chemotherapeutic drugs as compared with conventional intraperitoneal chemotherapy. Till now the drugs used in PIPAC for the treatment of the peritoneal carcinomatosis (PC) are cisplatin, doxorubicin, and oxaliplatin; as of yet, there are no in vivo data comparing different drug formulations and dosage schedules of PIPAC. Pegylated liposomal doxorubicin 1.5 mg/sm was aerosolized in PIPAC procedures. Results: Pharmacokinetics analysis of 10 procedures performed with conventional doxorubicin solution at the dose of 1.5 mg/m2 were compared to 15 procedures with the same dose of pegylated liposomal doxorubicin (PLD). Significant differences between experimental groups were detected by one-way ANOVA followed by Bonferroni correction; a p value < 0.05 was considered statistically significant. A statistically different doxorubicin tissue concentration was observed for the doxorubicin solution compared to pegylated liposomal doxorubicin in the right parietal peritoneum and right diaphragm. In the Caelyx® series a mean tissue concentration of 1.27 ± 1.33 mg/g was reported, while in the second one we registered a mean concentration of 3.1 ± 3.7 mg/g. Conclusions: The delivery of nano-particles in PIPAC was feasible, but pegylated liposomal concentrations are lower than standard doxorubicin formulation. Probably mechanical and physical properties of pressurized aerosol chemotherapy might alter their stability and cause structural disintegration.
Highlights
Peritoneal carcinomatosis (PC) is a clinical presentation both of different primary tumors such as colon-rectum, ovarian, appendix, stomach, pancreas, liver, and primitive peritoneal neoplasms such as diffuse peritoneal mesothelioma and primary peritoneal adenocarcinomas
“Pegylation” is the process whereby the doxorubicin-containing liposomes are enclosed within a polyethylene glycol (PEG) layer; pegylation protects the liposomes from detection by the mononuclear phagocyte system and provides a stabilization effect that reduces adhesion to cells, blood vessel walls, and other surfaces
At least 90% of pegylated liposomal doxorubicin (PLD) remains encapsulated within the liposomes, resulting in an extended half-life compared to conventional doxorubicin (Alberts et al, 2004)
Summary
Peritoneal carcinomatosis (PC) is a clinical presentation both of different primary tumors (synchronous or metachronous) such as colon-rectum, ovarian, appendix, stomach, pancreas, liver, and primitive peritoneal neoplasms such as diffuse peritoneal mesothelioma and primary peritoneal adenocarcinomas. Curative approach is reserved to a minority of selected patients, while most of patients are still treated with palliative intent (due to comorbidity, advanced stage of disease, age limits, availability of specialized centers). The edge between those two major PC features is sometimes unclear and new ways to treat the “gray-zone patients,” merging low-impact treatment and acceptable clinical results may be, probably, the near-future ideal approach to PC. Peritoneal carcinomatosis is a common metastatic pattern in ovarian, gastric, colorectal, and appendiceal cancer; systemic chemotherapy is the current standard of care for peritoneal metastatic disease; in a subset of patients its beneficial effect remains questionable.
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