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Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in combination with standard of care chemotherapy in primarily untreated chemo naive upper gi-adenocarcinomas with peritoneal seeding - a phase II/III trial of the AIO/CAOGI/ACO.

ABSTRACT: Background:Peritoneal metastasis is a common and dismal evolution of several gastrointestinal (GI) tumors, including gastric, colorectal, hepatobiliary, pancreatic, and other cancers. The therapy of peritoneal metastasis is largely palliative; with the aim of prolonging life and preserving its quality. In the meantime, a significant pharmacological advantage of intraperitoneal chemotherapy was documented in the preclinical model, and numerous clinical studies have delivered promising clinical results. Methods:This is a prospective, open, randomized multicenter phase III clinical study with two arms that aims to evaluate the effects of pressurized intraperitoneal aerosol chemotherapy (PIPAC) combined with systemic chemotherapy vs. intravenous systemic chemotherapy alone on patients with metastatic upper GI tumors with a peritoneal seeding. Upper GI-adenocarcinomas originated from biliary tract, pancreas and stomach, or esophago- gastric junction are eligible. Patients in the study are treated with standard of care systemic palliative chemotherapy (mFOLFOX6) vs. PIPAC with intravenous (i.v.) chemotherapy (mFOLFOX6). Patients in first line with first diagnosed peritoneal seeding are eligible. Primary outcome is progression free survival (PFS). Conclusions:PIPAC-procedure is explicit a palliative method but it delivers cytotoxic therapy like in hyperthermic intraperitoneal chemotherapy (HIPEC)-procedure directly to the tumor in a minimally invasive technique, without the need for consideration of the peritoneal-plasma barrier. The technique of PIPAC is minimally invasive and very gentle and the complete procedure takes only round about 45?min and, therefore, optimal in a clearly palliative situation where cure is not the goal. It is also ideal for using this approach in a first line situation, where deepest response should be achieved. The symbiosis of systemic therapy and potentially effective surgery has to be well-planned without deterioration of the patient due to aggressive way of surgery like in cytoreductive surgery (CRS)+HIPEC. Trial registration:EudraCT: 2018-001035-40.

SUBMITTER: Oliver Goetze T

PROVIDER: S-EPMC6404998 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in combination with standard of care chemotherapy in primarily untreated chemo naïve upper gi-adenocarcinomas with peritoneal seeding - a phase II/III trial of the AIO/CAOGI/ACO.

Oliver Goetze Thorsten T Al-Batran Salah-Eddin SE Pabst Urs U Reymond Marc M Tempfer Clemens C Bechstein Wolf O WO Bankstahl Ulli U Gockel Ines I Königsrainer Alfred A Kraus Thomas T Mönig Stefan P SP Rau Beate B Schwarzbach Matthias M Piso Pompiliu P

Pleura and peritoneum 20180608 2

<h4>Background</h4>Peritoneal metastasis is a common and dismal evolution of several gastrointestinal (GI) tumors, including gastric, colorectal, hepatobiliary, pancreatic, and other cancers. The therapy of peritoneal metastasis is largely palliative; with the aim of prolonging life and preserving its quality. In the meantime, a significant pharmacological advantage of intraperitoneal chemotherapy was documented in the preclinical model, and numerous clinical studies have delivered promising cli ...[more]

PMID: 30911658

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Project description: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.

Project description:BackgroundPeritoneal carcinomatosis (PC) is a common endpoint in both gastrointestinal and non-gastrointestinal cancers, and PC is treated as other systemic metastases - unfortunately with disappointing results and considerable side-effects. Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a new method of applying traditional chemotherapy, and preliminary data indicate that PIPAC is safe, able to stabilize or improve quality of life, and can induce an objectively measurable reduction in disease burden in PC.MethodsPIPAC-OPC2 is a prospectively controlled Phase II, single center, one-arm, open-label clinical trial investigating the treatment effect of PIPAC in patients with histological or cytological proven PC from gastrointestinal, ovarian or primary peritoneal cancer. Eligible patients will receive PIPAC in series of three using a combination of doxorubicin (1.5 mg/m2) and cisplatin (7.5 mg/m2) for non-colorectal cancer patients (PIPAC C/D), and oxaliplatin (92 mg/m2) in patients with PC of colorectal origin (PIPAC OX). Patients are monitored by: (1) repeated measurements of the Peritoneal Regression Grading Score (PRGS) in biopsies obtained from metal clips marked areas, (2) Quality-of-Life (QoL) questionnaires, (3) Magnetic Resonance Imaging (MRI) and (4) Prognostic Nutritional Index (PNI). Adverse events and surgical complications will be recorded according to the 30 days definition.ResultsThe primary outcome of PIPAC-OPC2 is to evaluate if PIPAC can induce major or complete response (PRGS 1 or 2) within a series of three PIPAC procedures. Secondarily this study investigates changes in QoL and MRI as a staging and response evaluation tool. The secondary outcomes will be used to create a model that may predict which of the patients will benefit from PIPAC treatment.ConclusionsIt is expected that PIPAC directed therapy can induce major or complete response in 50 % of patients with PC of colorectal origin and in 30 % of patients with PC of non-colorectal origin - and at the same time stabilize or even improve quality of life. This trial may provide data regarding the utility of MRI as a staging and response evaluation tool in patients with PC.Trial registrationThe study is registered with ClinicalTrials.gov Identifier NCT03287375 and the European Clinical Trials Database (EudraCT) number 2016-003394-18.

Project description:Objective: The objective of this study is to analyze oncological outcomes of patients with peritoneal metastases (PM) of colorectal origin treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). Background: PIPAC has been demonstrated to be a feasible and safe novel treatment for patients with PM of various origins. Only small series reports on survival after PIPAC by disease entity. Methods: International retrospective cohort study of consecutive patients with PM of colorectal origin. Outcome measures were overall survival (OS), radiological response according to Response Evaluation Criteria in Solid Tumors (RECIST), histological response (peritoneal regression grading score [PRGS]: complete response: 1–4: no response), change of peritoneal cancer index (PCI), and symptom control. Results: Seventeen eligible centers compiled 256 non-selected patients (mean age 61 [50.6–69.2], 43% female) and 606 procedures. Sixty-three percent were treated after 2 lines of chemotherapy, median PCI at PIPAC1 was 18 (interquartile range [IQR] = 10–27). Median OS was 19.00 months (IQR = 12.9–29.8) from diagnosis and 9.4 months (IQR = 4.5–16.8) from PIPAC1. One hundred and four of 256 patients (40.6%) had ≥3 procedures (per protocol [pp]) with the following outcomes at PIPAC3: RECIST: 59.3% partial response/stable, 40.7% progression; mean PRGS: 2.1 ± 0.9. Median PCI was 21 (IQR = 15–29) at baseline and 20 (IQR = 12–27) at PIPAC3 (P = 0.02). Fifty-six (54%) and 48 (46%) patients were symptomatic at baseline and PIPAC3, respectively (P = 0.267). Median OS for the pp cohort was 11.9 months (IQR = 10.7–15.0) from PIPAC1. Independent predictors for survival were radiological response (HR = 3.0; 95% CI = 1.6–5.7) and no symptoms (HR = 4.5, 95% CI = 2.2–9.1) at PIPAC3. Conclusions: Objective treatment response and encouraging survival were demonstrated after PIPAC for colorectal PM. Prospective registry data and comparative studies are now needed in to confirm these data.

Dataset Information

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in combination with standard of care chemotherapy in primarily untreated chemo naive upper gi-adenocarcinomas with peritoneal seeding - a phase II/III trial of the AIO/CAOGI/ACO.

Publications

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in combination with standard of care chemotherapy in primarily untreated chemo naïve upper gi-adenocarcinomas with peritoneal seeding - a phase II/III trial of the AIO/CAOGI/ACO.

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