Concomitant intraperitoneal and systemic chemotherapy for extensive peritoneal metastases of colorectal origin: protocol of the multicentre, open-label, phase I, dose-escalation INTERACT trial.

Autor:	de Boer NL; Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Brandt-Kerkhof ARM; Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Madsen EVE; Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Diepeveen M; Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van Meerten E; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van Eerden RAG; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., de Man FM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Bouamar R; Department of Hospital Pharmacy, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands., Koolen SLW; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.; Department of Hospital Pharmacy, Erasmus MC, Rotterdam, Zuid-Holland, The Netherlands., de Hingh IHJT; Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands., Bakkers C; Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands., Rovers KP; Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands., Creemers GM; Department of Medical Oncology, Catharina Cancer Institute, Eindhoven, The Netherlands., Deenen MJ; Department of Clinical Pharmacy, Catharina Hospital, Eindhoven, The Netherlands., Kranenburg OW; Department of Surgical Oncology and Utrecht Platform for Organoid Technology, UMC Utrecht Cancer Centre, Utrecht, The Netherlands., Constantinides A; Department of Surgical Oncology and Utrecht Platform for Organoid Technology, UMC Utrecht Cancer Centre, Utrecht, The Netherlands., Mathijssen RHJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Verhoef C; Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Burger JWA; Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands pim.burger@catharinaziekenhuis.nl.; Department of Surgery, Catharina Cancer Institute, Eindhoven, The Netherlands.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2019 Dec 08; Vol. 9 (12), pp. e034508. Date of Electronic Publication: 2019 Dec 08.
DOI:	10.1136/bmjopen-2019-034508
Abstrakt:	Introduction: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases of colorectal origin with a low/moderate abdominal disease load. In case of a peritoneal cancer index (PCI) score >20, CRS-HIPEC is not considered to be beneficial. Patients with a PCI >20 are currently offered palliative systemic chemotherapy. Previous studies have shown that systemic chemotherapy is less effective against peritoneal metastases than it is against haematogenous spread of colorectal cancer. It is suggested that patients with peritoneal metastases may benefit from the addition of intraperitoneal chemotherapy to systemic chemotherapy. Aim of this study is to establish the maximum tolerated dose of intraperitoneal irinotecan, added to standard of care systemic therapy for colorectal cancer. Secondary endpoints are to determine the safety and feasibility of this treatment and to establish the pharmacokinetic profile of intraperitoneally administered irinotecan. Methods and Analysis: This phase I, '3+3' dose-escalation, study is performed in two Dutch tertiary referral centres. The study population consists of adult patients with extensive peritoneal metastases of colorectal origin who have a good performance status and no extra-abdominal metastases. According to standard work-up for CRS-HIPEC, patients will undergo a diagnostic laparoscopy to score the PCI. In case of a PCI >20, a peritoneal access port will be placed in the abdomen of the patient. Through this port we will administer intraperitoneal irinotecan, in combination with standard systemic treatment consisting of 5-fluorouracil/leucovorin with oxaliplatin and the targeted agent bevacizumab. Therapy consists of a maximum of 12 cycles 2-weekly. Ethics and Dissemination: This study protocol is approved by a research medical ethics committee (Rotterdam, Netherlands) and the Dutch Competent Authority (CCMO, The Hague, Netherlands). The results of this trial will be submitted for publication in a peer-reviewed scientific journal. Trail Registration Number: NL6988 and NL2018-000479-33; Pre-results. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu