Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for the treatment of malignant mesothelioma

Abstract

BackgroundPatients with recurrent malignant epithelioid mesothelioma (MM) after surgery and standard chemotherapy with cisplatin and pemetrexed have limited treatment options.MethodsWe performed a retrospective cohort study of patients with recurrent MM undergoing Pressurized IntraPeritoneal/Thoracal Aerosol Chemotherapy (PIPAC/PITAC) with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2. Data were retrospectively collected in a prospective registry of patients undergoing PIPAC/PITAC. Study outcomes were microscopic tumor regression grade (TRG), survival and adverse events (v4.0 CTCAE).ResultsA total of 29 patients (m/f = 17/12) with MM with a mean age of 62.4 (range: 42 to 84) years were analyzed. A total of 74 PIPAC and 5 PITAC procedures were performed. The mean number of PIPAC applications was 2.5 (range: 0 to 10) per patient. Twenty patients (69%) had > 2 PIPAC procedure and were eligible for TRG analysis. TRG 1 to 4 was observed in 75% (15/20) of patients. Major regression (TRG 3) or complete regression (TRG 4) was observed in 20% and 10%, respectively. PIPAC induced significant tumor regression in 51.7% (15/29) of patients with a cumulative effect after repetitive PIPACs (PIPAC #1 vs. PIPAC #2: p = 0.001; PIPAC #1 vs. PIPAC #3: p = 0.001; PIPAC #1 vs. PIPAC #4: p = 0.001). Postoperative CTCAE grade 4 complications were observed in two patients (6.9%) who had cytoreductive surgery (CC2) and intraoperative PIPAC. One patient (3.4%) died due to postoperative kidney insufficiency. After a follow up of 14.4 (95% CI: 8.1 to 20.7) months after the last PIPAC/PITAC application, median overall survival was 26.6 (95% CI: 9.5 to 43.7) months (from the first application).ConclusionAfter prior abdominal surgery and systemic chemotherapy, repetitive PIPAC applications are feasible and safe for patients with end-stage MM. Furthermore, PIPAC induces significant histological regression of malignant mesothelioma in the majority of patients. PITAC is feasible, but its safety and efficacy to control malignant pleural effusion remain unclear.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4363-0) contains supplementary material, which is available to authorized users.

Intrathoracic aerosol chemotherapy via spray‑catheter

“…The treatment of PM is often interdisciplinary and includes oncologist, pulmonologists, surgeons, anesthesiologists and other specialists. Recently, pressurized intrathoracic aerosol chemotherapy (PITAC) has been introduced to the clinical setting as a modified version of the micropump © (MIP™; Reger Medizintechnik)-based pressurized intraperitoneal aerosol chemotherapy (PIPAC) (7). PITAC is currently used in PM patients who especially suffer from recurrent pleural effusions.…”

“…Following PITAC treatment, patients exhibited good results with a significant decrease or even remission of MPE production in the pleural cavity. Currently, only limited clinical data is available on the efficacy of intrathoracic aerosol chemotherapy by means of PITAC (7). In its present form, PITAC is defined as a surgical procedure requiring an operation room, a defined amount of surgical personnel, such as a general or thoracic surgeon and surgical assistants, and materials as well as the MIP™, a single-use, high-pressure injector pump.…”

Creating nanocrystallized chemotherapy: the differences in pressurized aerosol chemotherapy (PAC) via intracavitary (IAG) and extracavitary aerosol generation (EAG) regarding particle generation, morphology and structure

“…Recent studies have introduced preliminary results of aerosol particle applications for oncologic treatment of peritoneal [6] and pleural metastases [7] as well as bladder cancer [8]. The introduction of pressurized intraperitoneal aerosol chemotherapy (PIPAC) has also advanced efforts in investigating clinical applicability of nanocrystals.…”

MESOTIP: Phase II multicenter randomized trial evaluating the association of PIPAC and systemic chemotherapy vs. systemic chemotherapy alone as 1st-line treatment of malignant peritoneal mesothelioma

“…PIPAC was tested in the setting of malignant mesothelioma showing encouraging results. The safety was evaluated on 29 patients out of whom 7 were assigned to alternating systemic and PIPAC regimens [22].…”