Pressurized intraperitoneal aerosol chemotherapy for recurrent ovarian, fallopian or primary peritoneal cancer with peritoneal carcinomatosis: a narrative review.
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SUBMITTER: Oh S
PROVIDER: S-EPMC8033050 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC6404994 | biostudies-literature
Project description: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/m(2) and cisplatin 7.5 mg/m(2) (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.
| S-EPMC3929768 | biostudies-literature
Project description:BACKGROUND:Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment that applies chemotherapeutic drugs into the peritoneal cavity as an aerosol under pressure. It improves local bioavailability of chemotherapeutic drugs as compared with conventional intraperitoneal chemotherapy. It has been proved to be safe and feasible if performed as an exclusive treatment in patients affected by peritoneal carcinomatosis. The first results in patients treated with PIPAC associated with systemic chemotherapy are presented. METHODS:Between June 2015 and February 2016, 57 PIPAC applications with oxaliplatin or cisplatin?+?doxorubicin every 6 weeks at 37 °C and 12 mmHg for 30 min were performed. Forty PIPAC procedures performed in 14 patients were included in this study; thirteen patients were undergoing systemic chemotherapy with a wash-out interval of at least 2 weeks before and 1 week after each PIPAC. Safety, tolerability, and postoperative complications were assessed by collection of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) 2. RESULTS:Forty PIPAC administrations were performed in 14 patients with no major perioperative complications. CTCAE grades 1 and 2 were observed after six and eight procedures, respectively, for abdominal pain and nausea. Renal and hepatic functions were not impaired; no cumulative renal toxicity was observed after repeated PIPAC procedures in association with systemic chemotherapy. CONCLUSIONS:These preliminary data show that the association of PIPAC and systemic chemotherapy does not induce significant hepatic and renal toxicity. It allows inclusion of patients with extraperitoneal disease or at a high risk of developing it. Further studies are needed to assess whether this combination therapy could become part of the standard treatment for peritoneal carcinomatosis.
| S-EPMC4850728 | biostudies-literature
Project description:The treatment of peritoneal surface malignances has changed considerably over the last thirty years. Unfortunately, the palliative is the only current treatment for peritoneal carcinomatosis (PC). Two primary intraperitoneal chemotherapeutic methods are used. The first is combination of cytoreductive surgery (CRS) and Hyperthermic IntraPEritoneal Chemotherapy (HIPEC), which has become the gold standard for many cases of PC. The second is Pressurized IntraPeritoneal Aerosol Chemotheprapy (PIPAC), which is promising direction to minimally invasive as safedrug delivery. These methods were improved through multicenter studies and clinical trials that yield important insights and solutions. Major method development has been made through nanomedicine, specifically nanoparticles. Here, we are presenting the latest advances of nanoparticles and their application to precision diagnostics and improved treatment strategies for PC. These advances will likely develop both HIPEC and PIPAC methods that used for in vitro and in vivo studies. Several benefits of using nanoparticles will be discussed including: 1) Nanoparticles as drug delivery systems; 2) Nanoparticles and Near Infrred (NIR) Irradiation; 3) use of nanoparticles in perioperative diagnostic and individualized treatment planning; 4) use of nanoparticles as anticancer dressing's, hydrogels and as active beeds for optimal reccurence prevention; and 5) finally the curent in vitro and in vivo studies and clinical trials of nanoparticles. The current review highlighted use of nanoparticles as novel tools in improving drug delivery to be effective for treatment patients with peritoneal carcinomatosis.
| S-EPMC5652850 | biostudies-literature
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.
| S-EPMC10406066 | biostudies-literature
Project description:Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an emerging palliative treatment for patients with unresectable peritoneal metastases. Potential advantages of PIPAC over current treatment options are a homogeneous intraperitoneal distribution, low local and systemic toxicity, and enhanced tumour penetration. Given these possible benefits, PIPAC is increasingly implemented in many centres worldwide. Scientific research into PIPAC is currently available from in vitro/in vivo/in animal studies, retrospective cohorts in humans, and phase I and II studies in humans. There are no results from randomised trials comparing PIPAC with conventional treatment, such as palliative systemic therapy. This narrative review aimed to provide an overview of the currently available literature on PIPAC. In general, repetitive PIPAC was feasible and safe for patients and operating room personnel. Primary and secondary non-access rates varied from 0-17% and 0-15%, respectively. Iatrogenic bowel injury was observed in 0-3% of PIPAC procedures. CTCAE grade 1-2 complications were common, mostly consisting of abdominal pain, nausea, vomiting, and fatigue. CTCAE grade 3-4 complications were uncommon, occurring on 0-15% of PIPAC procedures. Post-operative mortality rates of 0-2% were reported. The risk of occupational exposure to cytotoxic drugs was very low when strict safety guidelines were followed. Clinical heterogeneity was high in most studies, since, in general, patients with unresectable peritoneal metastases from a variety of primary tumours were included. Also, patients received either PIPAC monotherapy or PIPAC combined with concomitant systemic therapy, and were able to receive PIPAC in any line of palliative treatment. Since the results were generally not stratified for these three important factors, this severely complicates the interpretation of results. Based on the current literature, PIPAC may be regarded as a promising palliative treatment option in patients with diffuse peritoneal metastases. Initial results show that it is feasible and safe. However, well designed and (ideally) randomized controlled trials are urgently needed to determine the additional value of PIPAC in this setting. Until then, PIPAC should preferably be performed in the setting of clinical trials.
| S-EPMC8100694 | biostudies-literature
Project description:Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an innovative approach for treating peritoneal carcinomatosis that applies chemotherapeutic drugs into the peritoneal cavity as an under-pressure airflow. It improves local bioavailability of cytostatic drugs as compared to conventional intraperitoneal chemotherapy. The aim of this study is to prove feasibility, efficacy and safety of this new treatment. Patients included in the analysis underwent at least two single port PIPAC procedures; drugs used were Oxaliplatin for colorectal cancers and Cisplatin + Doxorubicin for ovarian, gastric, and primary peritoneal cancers. The primary endpoint was the Disease Control Rate according to the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Secondary significant endpoints were overall and progression free survival, tumor regression on histology, and quality of life. Safety and tolerability were assessed according to the Common Terminology Criteria for Adverse Events 4. Sixty-three patients were enrolled in this trial. Forty patients (100 PIPAC) were eligible for analysis. Twenty patients were undergoing systemic chemotherapy. Fourteen patients reported an objective response (35%). Median overall survival was 18.1 months; median progression-free survival was 7.4 months. Minor morbidity was observed in seven procedures. Grade 3 complications occurred in two patients, and grade 4 in one patient submitted to reoperation. Single-port PIPAC is feasible, safe, and easy to perform. The combined treatment based on systemic chemotherapy and PIPAC does not induce significant hepatic and renal toxicity and can be considered a valid therapeutic option in patients with advanced peritoneal disease. Further studies on the use of PIPAC alone, possibly with different drug dosages, may define the real effectiveness of the procedure.
| S-EPMC7277495 | biostudies-literature
Project description:BACKGROUND:Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is used in the palliative treatment of peritoneal metastasis. The combination of intraperitoneal and systemic chemotherapy seems rational, and the aim of this systematic review was to compare PIPAC directed monotherapy with a bidirectional treatment approach (PIPAC in combination with systemic chemotherapy). Main outcomes were survival and quality of life. METHODS:A systematic literature search in Medline, Embase, Cochrane and the "Pleura and Peritoneum" was conducted and analyzed according to PRISMA guidelines. Studies in English reporting on bidirectional treatment with PIPAC and systemic chemotherapy and published before April 2019 were included. RESULTS:Twelve studies with a total of 386 patients were included. None were specifically designed to compare mono- versus bidirectional treatment, but 44% of the patients received bidirectional treatment. This was more frequent in women (non-gynecological cancers) and one-third of the bidirectional treated patients had received no prior chemotherapy. Data from the included studies provided no conclusions regarding survival or quality of life. CONCLUSION:Bidirectional treatment with PIPAC and systemic chemotherapy is practised and feasible, and some patients are enrolled having received no prior systemic chemotherapy for their PM. The difficulty in drawing any conclusions based on this systematic review has highlighted the urgent need to improve and standardize reports on PIPAC directed therapy. We have, therefore, constructed a list of items to be considered when reporting on clinical PIPAC research. TRIAL REGISTRATION:International Prospective Register of Systematic Reviews, PROSPERO. Registration number: 90352, March 5, 2018.
| S-EPMC7011374 | biostudies-literature
Project description:BackgroundPressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique of intraperitoneal chemotherapy. First results obtained with PIPAC in patients with advanced peritoneal metastasis (PM) from gastric cancer (GC) are presented.MethodsRetrospective analysis: Sixty PIPAC were applied in 24 consecutive patients with PM from GC. 67 % patients had previous surgery, and 79 % previous platinum-based systemic chemotherapy. Mean Peritoneal Carcinomatosis Index (PCI) of 16 ± 10 and 18/24 patients had signet-ring GC. Cisplatin 7.5 mg/m(2) and doxorubicin 1.5 mg/m(2) were given for 30 min at 37 °C and 12 mmHg at 6 week intervals. Outcome criteria were survival, adverse events, and histological tumor response.ResultsMedian follow-up was 248 days (range 105-748), and median survival time was 15.4 months. Seventeen patients had repeated PIPAC, and objective tumor response was observed in 12 (12/24 = 50 %): no vital tumor cells = 6, major pathological response = 6, minor response = 3. Postoperative adverse events > CTCAE 2 were observed in 9 patients (9/24, 37.5 %). In 3/17 patients, a later PIPAC could not be performed due to non-access. Two patients (ECOG 3 and 4) died in the hospital due to disease progression.ConclusionPIPAC with low-dose cisplatin and doxorubicin was safe and induced objective tumor regression in selected patients with PM from recurrent, platinum-resistant GC. First survival data are encouraging and justify further clinical studies in this indication.
| S-EPMC4722080 | biostudies-literature
Project description:IntroductionPressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug delivery system with superior pharmacological properties for treating peritoneal metastasis (PM). Safety and efficacy results of PIPAC with cisplatin/doxorubicin or oxaliplatin from a registry cohort are presented.MethodsIRB-approved registry study. Retrospective analysis. No predefined inclusion criteria, individual therapeutic recommendation by the interdisciplinary tumor board. Safety assessment with CTCAE 4.0. Histological assessment of tumor response by an independent pathologist using the 4-tied peritoneal regression grading system (PRGS). Mean PRGS and ascites volume were assessed at each PIPAC.ResultsA total of 142 PIPAC procedures were scheduled in 71 consecutive patients with PM from gastric (n = 26), colorectal (n = 17), hepatobiliary/pancreatic (n = 9), ovarian (n = 6), appendiceal (n = 5) origin, pseudomyxoma peritonei (n = 4), and other tumors (n = 3). Mean age was 58 ± 13 years. Patients were heavily pretreated. Mean PCI was 19 ± 13. Laparoscopic nonaccess rate was 11/142 procedures (7.7%). Mean number of PIPAC/patient was 2. All patients were eligible for safety analysis. There was no procedure-related mortality. There were 2.8% intraoperative and 4.9% postoperative complications. 39 patients underwent more than one PIPAC and were eligible for efficacy analysis, and PRGS could be assessed in 36 of them. In 24 patients (67%), PRGS improved or remained unchanged at PIPAC#2, reflecting tumor regression or stable disease. Ascites was present in 24 patients and diminished significantly under therapy. Median survival was 11.8 months (95% CI: 7.45-16.2 months) from PIPAC#1.ConclusionPIPAC is feasible, safe, and well-tolerated and can induce histological regression in a significant proportion of pretreated PM patients. This trial is registered with NCT03210298.
| S-EPMC6220392 | biostudies-literature