{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:24:53Z","timestamp":1792452293470,"version":"4.5.0"},"reference-count":20,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Standard treatment for patient with peritoneal metastases from colorectal cancer is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). In recent years, the efficacy of oxaliplatin-based HIPEC has been challenged. An intensified HIPEC (oxaliplatin+irinotecan) in combination with early postoperative intraperitoneal chemotherapy (EPIC) has shown increased recurrence-free survival in retrospective studies. The aim of this trial is to develop a new HIPEC\/EPIC regimen and evaluate its effect on morbidity, oncological outcome, and quality-of-life (QoL). This study is designed as a combined phase I\/III multicenter randomized trial (RCT) of patients with peritoneal metastases from colorectal cancer eligible for CRS-HIPEC. An initial phase I dose escalation study, designed as a 3+3 stepwise escalation, will determine the maximum tolerable dose of 5-Fluorouracil (5-FU) as 1-day EPIC, enrolling a total of 15\u201330 patients in 5 dose levels. In the phase III efficacy study, patients are randomly assigned intraoperatively to either the standard treatment with oxaliplatin HIPEC (control arm) or oxaliplatin\/irinotecan-HIPEC in combination with single dose of 1-day 5-FU EPIC (experimental arm). 5-FU is administered intraoperatively after CRS-HIPEC and closure of the abdomen. The primary endpoint is 12-month recurrence-free survival. Secondary endpoints include 5-year overall survival, 5-year recurrence-free survival (registry based), postoperative complications, and QoL up to 3 years after study treatment. This phase I\/III trial aims to identify a more effective treatment of colorectal peritoneal metastases by combination of HIPEC and EPIC.<\/jats:p>","DOI":"10.1371\/journal.pone.0294018","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T18:29:29Z","timestamp":1709576969000},"page":"e0294018","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Efficacy of hyperthermic intraperitoneal chemotherapy in colorectal cancer: A phase I and III open label randomized controlled registry-based clinical trial protocol"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6513-8228","authenticated-orcid":true,"given":"Lana","family":"Ghanipour","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Jansson Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per J.","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Nordenvall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Erik","family":"Fr\u00f6din","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1466-1486","authenticated-orcid":true,"given":"Elinor","family":"Bexe Lindskog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Asplund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torbj\u00f6rn","family":"Swartling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Graf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helgi","family":"Birgisson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingvar","family":"Syk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Verwaal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Br\u00e4ndstedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Cashin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"issue":"2","key":"pone.0294018.ref001","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S1470-2045(20)30599-4","article-title":"Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial.","volume":"22","author":"UNICANCER-GI Group and BIG Renape Group.","year":"2021","journal-title":"Lancet Oncol"},{"issue":"Suppl 1","key":"pone.0294018.ref002","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.21037\/jgo-2020-05","article-title":"Hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal and appendiceal peritoneal metastases: lessons learned from PRODIGE 7.","volume":"12","author":"P Cashin","year":"2021","journal-title":"J Gastrointest Oncol."},{"issue":"3","key":"pone.0294018.ref003","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1056\/NEJMoa1708618","article-title":"Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer","volume":"378","author":"WJ van Driel","year":"2018","journal-title":"N Engl J Med"},{"issue":"6","key":"pone.0294018.ref004","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1245\/s10434-011-1631-5","article-title":"Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial","volume":"18","author":"XJ Yang","year":"2011","journal-title":"Ann Surg Oncol"},{"issue":"2","key":"pone.0294018.ref005","doi-asserted-by":"crossref","first-page":"516","DOI":"10.21037\/jgo-20-494","article-title":"Oxaliplatin-based Hyperthermic Intraperitoneal Chemotherapy with Single Drug Versus Multiple Drug Treatment for Colorectal Cancer with Peritoneal Metastases: An Observational Cohort Study.","volume":"12","author":"P Fr\u00fchling","year":"2021","journal-title":"J Gastrointest Oncol"},{"key":"pone.0294018.ref006","article-title":"Hyperthermic Intraperitoneal Chemotherapy in Colorectal Cancer.","author":"Oliver M. 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