Intraperitoneal Chemotherapy of Peritoneal Carcinomatosis Using Pressurized Aerosol as an Alternative to Liquid Solution: First Evidence for Efficacy

Abstract

BackgroundPeritoneal carcinomatosis (PC) is an unmet medical need. Despite recent improvements, systemic chemotherapy has limited efficacy. We report the first application of intraperitoneal chemotherapy as a pressurized aerosol in human patients. MethodsThree end-stage patients with advanced PC from gastric, appendiceal, and ovarian origin were treated as a compassionate therapy. All patients had received previous systemic chemotherapy. A pressurized aerosol of CO2 loaded with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2 (pressurized intraperitoneal aerosol chemotherapy, PIPAC) was applied into the abdomen for 30 min at a pressure of 12 mmHg and a temperature of 37 °C.ResultsNo side-effects >2 CTCAE were observed, and the procedures were well tolerated. Early hospital discharge was possible (days 2–5). Nuclear presence of doxorubicin was documented throughout the peritoneum, reaching high local concentration (≤4.1 μmol/g) and plasma concentration was low (4.0–6.2 ng/ml). PIPAC created no significant adhesions, could be repeated, and was applied 6×, 4×, and 2×. Two patients showed a complete and one a partial histological remission. Mean survival after the first PIPAC was 288 days. One patient is alive after 567 days.ConclusionsPIPAC shows superior pharmacological properties with high local concentration and low systemic exposure. PIPAC can induce regression of PC in chemoresistant tumors, using 10 % of a usual systemic dose.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-013-3213-1) contains supplementary material, which is available to authorized users.

Nanomedicine-based intraperitoneal therapy for the treatment of peritoneal carcinomatosis — Mission possible?

“…The aerosol form accomplishes homogeneous drug distribution [30], while it is believed that the high intra-abdominal pressure enhances tissue penetration and antitumor effects [31,32]. As a consequence, a low dose of chemotherapy can be used, causing low systemic drug uptake and toxicity [29,33]. Interestingly, Solass and coworkers indeed showed that clinical PIPAC therapy with Doxorubicin achieves high tissue drug concentrations, even though a relatively low dose is nebulized [29].…”

“…As a consequence, a low dose of chemotherapy can be used, causing low systemic drug uptake and toxicity [29,33]. Interestingly, Solass and coworkers indeed showed that clinical PIPAC therapy with Doxorubicin achieves high tissue drug concentrations, even though a relatively low dose is nebulized [29].…”

A new ex vivo model for optimizing distribution of therapeutic aerosols: the (inverted) bovine urinary bladder

“…Application of the therapeutic aerosol was performed as described previously [1]. Shortly, 30 mL of a saline solution stained with methylene blue 0.0003 % were aerosolized with a nebulizer (Capnopen ® , Capnomed, Villingendorf, Germany) at a pressure of 15 mmHg and room temperature (24.5°C) and maintained for 15 min.…”

“…Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) has received much attention in recent years due to its superior pharmacological properties, which offers potential clinical advantages [1]. In particular, locoregional administration of a therapeutic substance as an aerosol under pressure allows higher tissue penetration, optimal exposition of the surface of the target organ to the drug, dose reduction and low systemic exposure.…”

Single-port access for Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC): technique, feasibility and safety

“…Compared with conventional IPC using catheters or to Hyperthermic IntraPeritoneal Chemotherapy (HIPEC), PIPAC achieves a more homogeneous distribution of the drug onto the exposed peritoneal surfaces [5]. Moreover, PIPAC increases drug penetration into the peritoneal tissue by application of an artificial hydrostatic intraperitoneal pressure [6,7].…”