98. Perioperative outcomes of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal carcinomatosis: PRODIGE 7 randomized trial

Quénet, François; Élias, Dominique; Roca, Lise; Goéré, D.; Ghouti, Laurent; Pocard, Marc; Facy, Olivier; Arvieux, C.; Lorimier, G.; Pezet, Denis; Marchal, Frédéric; Loi, Valeria; Méeus, Pierre; Forges, Hélène de; Stanbury, Trevor; Paineau, J; Gléhen, Olivier

doi:10.1016/j.ejso.2016.06.105

Cited by 6 publications

(8 citation statements)

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“…This procedure was first introduced by Paul Sugarbaker for the treatment of Pseudomyxoma Peritonei (PMP) ( 46 ) and has since been widely adapted to treat PM from multiple cancer types. However, the added value of HIPEC over CRS alone for the treatment of colorectal PM has recently been questioned in the PRODIGE7 trial ( 47 ). CRS with or without HIPEC is a high-cost procedure that is associated with considerable morbidity and mortality rates ( 48 , 49 ).…”

Section: Treatmentmentioning

confidence: 99%

“…A clear benefit of the HIPEC procedure following CRS has recently been demonstrated in patients with PM from ovarian cancer ( 58 ). However, the PRODIGE7 trial failed to prove an additional value of HIPEC in patients treated for PM from CRC ( 47 ). However a post-hoc subgroups analysis showed that HIPEC improved relapse-free and overall survival specifically in a subgroup with intermediate PCI ( 11 – 15 ), suggesting that future optimization of the procedure should focus on this subgroup with the potential for (near-) complete surgical PM resection.…”

Section: Treatmentmentioning

confidence: 99%

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Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges

2021

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The presence of peritoneal metastases (PM) in patients with colorectal cancer (CRC) is associated with an extremely poor prognosis. The diagnosis of PM is challenging, resulting in an underestimation of their true incidence. While surgery can be curative in a small percentage of patients, effective treatment for non-operable PM is lacking, and clinical and pre-clinical studies are relatively sparse. Here we have defined the major clinical challenges in the areas of risk assessment, detection, and treatment. Recent developments in the field include the application of organoid technology, which has generated highly relevant pre-clinical PM models, the application of diffusion-weighted MRI, which has greatly improved PM detection, and the design of small clinical proof-of-concept studies, which allows the efficient testing of new treatment strategies. Together, these developments set the stage for starting to address the clinical challenges. To help structure these efforts, a translational research framework is presented, in which clinical trial design is based on the insight gained from direct tissue analyses and pre-clinical (organoid) models derived from CRC patients with PM. This feed-forward approach, in which a thorough understanding of the disease drives innovation in its clinical management, has the potential to improve outcome in the years to come.

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Section: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges

2021

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“…With regards to the chemotherapy regimen used in this study, the results of the recently published PRODIGE-7 trial may question the intraperitoneal use of oxaliplatin (combined with 5-fluorouracil and leucovorin) in patients with CPM. 37 However, in contrast with PRODIGE-7, patients in the present study are either systemic therapy-naïve or had undergone a mandatory 6-month wash-out period of systemic therapy. As a result, the previously untreated patients in this study may be more sensitive to intraperitoneal oxaliplatin than patients in the PRODIGE-7 trial.…”

Section: Discussionmentioning

confidence: 94%

First-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy (oxaliplatin) for isolated unresectable colorectal peritoneal metastases: protocol of a multicentre, single-arm, phase II study (CRC-PIPAC-II)

et al. 2021

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IntroductionDespite its increasing use, first-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX), hereinafter referred to as first-line bidirectional therapy, has never been prospectively investigated in patients with colorectal peritoneal metastases (CPM). As a first step to address this evidence gap, the present study aims to assess the safety, feasibility, antitumour activity, patient-reported outcomes, costs and systemic pharmacokinetics of first-line bidirectional therapy in patients with isolated unresectable CPM.Methods and analysisIn this single-arm, phase II study in two Dutch tertiary referral centres, 20 patients are enrolled. Key eligibility criteria are a good performance status, pathologically proven isolated unresectable CPM, no previous palliative systemic therapy for colorectal cancer, no (neo)adjuvant systemic therapy ≤6 months prior to enrolment and no previous pressurised intraperitoneal aerosol chemotherapy (PIPAC). Patients receive three cycles of bidirectional therapy. Each cycle consists of 6 weeks first-line palliative systemic therapy at the medical oncologists’ decision (CAPOX-bevacizumab, FOLFOX-bevacizumab, FOLFIRI-bevacizumab or FOLFOXIRI-bevacizumab) followed by ePIPAC-OX (92 mg/m2) with an intraoperative bolus of intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Study treatment ends after the third ePIPAC-OX. The primary outcome is the number of patients with—and procedures leading to—grade ≥3 adverse events (Common Terminology Criteria for Adverse Events V.5.0) up to 4 weeks after the last procedure. Key secondary outcomes include the number of bidirectional cycles in each patient, treatment-related characteristics, grade ≤2 adverse events, tumour response (histopathological, cytological, radiological, biochemical, macroscopic and ascites), patient-reported outcomes, systemic pharmacokinetics of oxaliplatin, costs, progression-free survival and overall survival.Ethics and disseminationThis study is approved by the Dutch competent authority, a medical ethics committee and the institutional review boards of both study centres. Results will be submitted for publication in peer-reviewed medical journals and presented to patients and healthcare professionals.Trial registration numberNL8303.

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“…Even if peritoneal carcinomatosis is a poor prognostic index, its responsiveness to chemotherapy has been documented [ 35 , 36 ]. A debate is ongoing regarding systemic and intraperitoneal chemotherapy [ 36 , 37 ], with the data from the Prodige 7 trial suggesting similar results between the two [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Hepatic and Extrahepatic Colorectal Metastases Have Discordant Responses to Systemic Therapy. Pathology Data from Patients Undergoing Simultaneous Resection of Multiple Tumor Sites

Viganò

Corleone

Darwish

et al. 2021

Cancers

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Background: Systemic therapy is the standard treatment for patients with hepatic and extrahepatic colorectal metastases. It is assumed to have the same effectiveness on all disease foci, independent of the involved organ. The present study aims to compare the response rates of hepatic and extrahepatic metastases to systemic therapy. Methods: All consecutive patients undergoing simultaneous resection of hepatic and extrahepatic metastases from colorectal cancer after oxaliplatin- and/or irinotecan-based preoperative chemotherapy were analyzed. All specimens were reviewed. Pathological response to chemotherapy was classified according to tumor regression grade (TRG). Results: We analyzed 45 patients undergoing resection of 134 hepatic and 72 extrahepatic metastases. Lung and lymph node metastases had lower response rates to chemotherapy than liver metastases (TRG 4–5 95% and 100% vs. 67%, p = 0.008, and p = 0.006). Peritoneal metastases had a higher pathological response rate than liver metastases (TRG 1–3 66% vs. 33%, p < 0.001) and non-hepatic non-peritoneal metastases (3%, p < 0.001). Metastases site was an independent predictor of pathological response to systemic therapy. Conclusions: Response to chemotherapy of distant metastases from colorectal cancer varies in different organs. Systemic treatment is highly effective for peritoneal metastases, more so than liver metastases, while it has a very poor impact on lung and lymph node metastases.

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98. Perioperative outcomes of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal carcinomatosis: PRODIGE 7 randomized trial

Cited by 6 publications

References 0 publications

Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges

Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges

First-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy (oxaliplatin) for isolated unresectable colorectal peritoneal metastases: protocol of a multicentre, single-arm, phase II study (CRC-PIPAC-II)

Hepatic and Extrahepatic Colorectal Metastases Have Discordant Responses to Systemic Therapy. Pathology Data from Patients Undergoing Simultaneous Resection of Multiple Tumor Sites

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