title: Treatment strategies in colorectal cancer patients with initially unresectable liver-only metastases, a study protocol of the randomised phase 3 CAIRO5 study of the Dutch Colorectal Cancer Group (DCCG).
abstract: BACKGROUND
  Colorectal cancer patients with unresectable liver-only metastases may be cured after downsizing of metastases by neoadjuvant systemic therapy. However, the optimal neoadjuvant induction regimen has not been defined, and the lack of consensus on criteria for (un)resectability complicates the interpretation of published results.
  
  
  METHODS
  CAIRO5 is a multicentre, randomised, phase 3 clinical study. Colorectal cancer patients with initially unresectable liver-only metastases are eligible, and will not be selected for potential resectability. The (un)resectability status is prospectively assessed by a central panel consisting of at least one radiologist and three liver surgeons, according to predefined criteria. Tumours of included patients will be tested for RAS mutation status. Patients with RAS wild type tumours will be treated with doublet chemotherapy (FOLFOX or FOLFIRI) and randomised between the addition of either bevacizumab or panitumumab, and patients with RAS mutant tumours will be randomised between doublet chemotherapy (FOLFOX or FOLFIRI) plus bevacizumab or triple chemotherapy (FOLFOXIRI) plus bevacizumab. Radiological evaluation to assess conversion to resectability will be performed by the central panel, at an interval of two months. The primary study endpoint is median progression-free survival. Secondary endpoints are the R0/1 resection rate, median overall survival, response rate, toxicity, pathological response of resected lesions, postoperative morbidity, and correlation of baseline and follow-up evaluation with respect to outcomes by the central panel.
  
  
  CONCLUSIONS
  CAIRO5 is a prospective multicentre trial that investigates the optimal systemic induction therapy for patients with initially unresectable, liver-only colorectal cancer metastases.
  
  
  BACKGROUND
  CAIRO 5 is registered at European Clinical Trials Database (EudraCT) (2013-005435-24). CAIRO 5 is registered at ClinicalTrials.gov: NCT02162563 , June 10, 2014.
authors.affiliation: Department of Surgery, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. j.huiskens@amc.nl.|Department of Medical Oncology, Academic Medical Centre, Amsterdam, the Netherlands. j.huiskens@amc.nl.
authors.forename: Joost
authors.initials: J
authors.lastname: Huiskens
authors.affiliation: Department of Surgery, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. t.m.vangulik@amc.nl.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: van Gulik
authors.affiliation: Department of Radiology, Academic Medical Centre, Amsterdam, the Netherlands. k.p.vanlienden@amc.uva.nl.
authors.forename: Krijn P
authors.initials: KP
authors.lastname: van Lienden
authors.affiliation: Department of Radiology, Academic Medical Centre, Amsterdam, the Netherlands. m.r.engelbrecht@amc.uva.nl.
authors.forename: Marc R W
authors.initials: MR
authors.lastname: Engelbrecht
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, the Netherlands. ga.meijer@vumc.nl.
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: Meijer
authors.affiliation: Department of Pathology, VU University Medical Centre, Amsterdam, the Netherlands. nct.vangrieken@vumc.nl.
authors.forename: Nicole C T
authors.initials: NC
authors.lastname: van Grieken
authors.affiliation: Netherlands Comprehensive Cancer Organisation, Utrecht, the Netherlands. j.schriek@iknl.nl.
authors.forename: Jonne
authors.initials: J
authors.lastname: Schriek
authors.affiliation: Netherlands Comprehensive Cancer Organisation, Utrecht, the Netherlands. a.keijser@iknl.nl.
authors.forename: Astrid
authors.initials: A
authors.lastname: Keijser
authors.affiliation: Netherlands Comprehensive Cancer Organisation, Utrecht, the Netherlands. l.mol@iknl.nl.
authors.forename: Linda
authors.initials: L
authors.lastname: Mol
authors.affiliation: Department of Surgery, UMCU, Utrecht, the Netherlands. i.q.molenaar@umcutrecht.nl.
authors.forename: I Quintus
authors.initials: IQ
authors.lastname: Molenaar
authors.affiliation: Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. c.verhoef@erasmusmc.nl.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Verhoef
authors.affiliation: Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. k.p.de.jong@umcg.nl.
authors.forename: Koert P
authors.initials: KP
authors.lastname: de Jong
authors.affiliation: Department of Surgery, MUMC, Maastricht, the Netherlands. chc.dejong@mumc.nl.
authors.forename: Kees H C
authors.initials: KH
authors.lastname: Dejong
authors.affiliation: Department of Surgery, VU University Medical Centre, Amsterdam, the Netherlands. g.kazemier@vumc.nl.
authors.forename: Geert
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authors.lastname: Kazemier
authors.affiliation: Department of Surgery, Netherlands Cancer Institute, Amsterdam, the Netherlands. t.ruers@nki.nl.
authors.forename: Theo M
authors.initials: TM
authors.lastname: Ruers
authors.affiliation: Department of Surgery, Radboud University Medical Center, Nijmegen, the Netherlands. hans.dewilt@radboudumc.nl.
authors.forename: Johanus H W
authors.initials: JH
authors.lastname: de Wilt
authors.affiliation: Department of Biostatistics, Netherlands Cancer Institute, Amsterdam, the Netherlands. h.v.tinteren@nki.nl.
authors.forename: Harm
authors.initials: H
authors.lastname: van Tinteren
authors.affiliation: Department of Medical Oncology, Academic Medical Centre, Amsterdam, the Netherlands. c.punt@amc.nl.
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000068258:Bevacizumab / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077544:Panitumumab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D000077544:Panitumumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin