Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)-directed treatment of peritoneal metastasis in end-stage colo-rectal cancer patients

Abstract

BackgroundPressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) represents a novel approach to intraperitoneal chemotherapy. Hereby results, obtained with PIPAC in patients with advanced peritoneal metastasis (PM) from colorectal cancer (CRC), are presented.MethodsData from CRC patients (n = 24) included in the prospective PIPAC-OPC1 and PIPAC-OPC2 trials are reported. Oxaliplatin 92 mg/m2 was administered at 4-6-week intervals. A CE certified nebulizer was used to aerosolize the chemotherapeutics. Outcome criteria were objective tumor response, survival and adverse events.ResultsRetrospective analysis of 74 PIPAC procedures carried out in 24 consecutive patients with PM from CRC included from October 2015 to February 2019. Five patients had still the primary tumor in situ, and 22 patients had received palliative systemic chemotherapy. Nineteen patients completed more than two PIPAC procedures, and objective tumor response according to the histological Peritoneal Regression Grading Score (PRGS) was observed in 67% of the patients, while 21% had stable disease. Four patients (21%) had complete response (mean PRGS = 1 and negative cytology). We recorded a median survival of 37.6 (range 7.3–48.9) months from the time of PM diagnosis, whereas it was 20.5 (range 0.13–34.7) months following the first PIPAC session. Minor postoperative complications were noted, and few were considered causally related to the PIPAC treatment. However, two cases of severe postoperative complications were recorded (urosepsis and iatrogenic bowel perforation).ConclusionsPIPAC with low-dose oxaliplatin can induce objective tumor regression in selected patients with advanced PM from colorectal cancer.

Development of rotational intraperitoneal pressurized aerosol chemotherapy to enhance drug delivery into the peritoneum

“…PIPAC has been suggested to be useful as palliative therapy for PM of recurrent or refractory solid tumors, which may lead to histologic regression, and thereby improve the quality of life (Tempfer et al., 2015 ; Horvath et al., 2018 ; Alyami et al., 2020 ; Ellebaek et al., 2020 ). Even if chemotherapeutic agents shown to be resistant in intravenous chemotherapy are used again in PIPAC, the agents may be absorbed into the peritoneal tumors by passive diffusion, which can be effective for treating PM by maintaining higher concentrations within tumor tissues while minimizing systemic absorption (Yan et al., 2010 ; Alyami et al., 2019 ).…”

Histological regression of gastrointestinal peritoneal metastases after systemic chemotherapy

“…The Peritoneal Regression Grading Score (PRGS) was initially developed to quantify PM’s histological response to palliative intraperitoneal chemotherapy [ 8 ]. This study demonstrated that PRGS can also be used for measuring the objective response of PM to systemic, intravenous chemotherapy.…”

“…A generic, unique score for assessing histological tumor response to chemotherapy in PM makes sense because of the clinical impact of histological response to therapy and because the organ of metastasis (peritoneum) is the same [ 3 ]. The PRGS has been the object of a multi-institutional validation study [ 4 ] and is now diffusing into clinical practice [ 8 , 14 ], [ 15 ], [ 16 ], [ 17 ], [ 18 ], [ 19 ], [ 20 ]. The PRGS is increasingly used as secondary [ 21 ], [ 22 ], [ 23 ], [ 24 ], or even as primary outcome criteria [ 25 ] in clinical studies on PM.…”

PIPAC (Pressurized Intraperitoneal Aerosol Chemotherapy) en el tratamiento de la carcinomatosis peritoneal. Primeros casos en Chile.

“…Se ha reportado reducción significativa de ascitis, dolor, distensión abdominal y otros síntomas gastrointestinales 7 . En el tratamiento de metástasis peritoneales de origen colorrectal ha destacado la negativización de los estudios citológicos para células malignas, regresión tumoral y disminución de la ascitis y una mediana de sobrevida de 27,6 meses (10,2-47) 8 .…”