{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:27:45Z","timestamp":1792787265918,"version":"4.5.0"},"reference-count":42,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T00:00:00Z","timestamp":1617062400000},"content-version":"unspecified","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"St. Antonius Research Foundation","award":["2019.01"],"award-info":[{"award-number":["2019.01"]}]},{"name":"Catharina Research Foundation","award":["CZE-2020.02"],"award-info":[{"award-number":["CZE-2020.02"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2021,3,12]]},"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Despite 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      In 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 \u22646 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\u2019 decision (CAPOX-bevacizumab, FOLFOX-bevacizumab, FOLFIRI-bevacizumab or FOLFOXIRI-bevacizumab) followed by ePIPAC-OX (92 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) with an intraoperative bolus of intravenous leucovorin (20 mg\/m2) and 5-fluorouracil (400 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ). Study treatment ends after the third ePIPAC-OX. The primary outcome is the number of patients with\u2014and procedures leading to\u2014grade \u22653 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 \u22642 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NL8303.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-044811","type":"journal-article","created":{"date-parts":[[2021,3,30]],"date-time":"2021-03-30T13:05:35Z","timestamp":1617109535000},"page":"e044811","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["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)"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct04329494","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03868228","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2692-0994","authenticated-orcid":false,"given":"Robin J.","family":"Lurvink","sequence":"first","affiliation":[{"name":"Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulien","family":"Rauwerdink","sequence":"additional","affiliation":[{"name":"Department of Surgery, Sint Antonius Ziekenhuis, Nieuwegein, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8174-2134","authenticated-orcid":false,"given":"Koen P.","family":"Rovers","sequence":"additional","affiliation":[{"name":"Department of Surgery, Catharina Hospital, Eindhoven, The 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