title: Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial.
abstract: BACKGROUND
  The optimum use of cytotoxic drugs for advanced colorectal cancer has not been defined. Our aim was to investigate whether combination treatment is better than sequential administration of the same drugs in patients with advanced colorectal cancer.
  
  
  METHODS
  We randomly assigned 820 patients with advanced colorectal cancer to receive either first-line treatment with capecitabine, second-line irinotecan, and third-line capecitabine plus oxaliplatin (sequential treatment; n=410) or first-line treatment capecitabine plus irinotecan and second-line capecitabine plus oxaliplatin (combination treatment; n=410). The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov with the number NCT00312000.
  
  
  RESULTS
  17 patients (nine in the sequential treatment group, eight in the combination group) were found to be ineligible and were excluded from the analysis. 675 (84%) patients died during the study: 336 in the sequential group and 339 in the combination group. Median overall survival was 16.3 (95% CI 14.3-18.1) months for sequential treatment and 17.4 (15.2-19.2) months for combination treatment (p=0.3281). The hazard ratio for combination versus sequential treatment was 0.92 (95% CI 0.79-1.08; p=0.3281). The frequency of grade 3-4 toxicity over all lines of treatment did not differ significantly between the two groups, except for grade 3 hand-foot syndrome, which occurred more often with sequential treatment than with combination treatment (13%vs 7%; p=0.004).
  
  
  CONCLUSIONS
  Combination treatment does not significantly improve overall survival compared with the sequential use of cytotoxic drugs in advanced colorectal cancer. Thus sequential treatment remains a valid option for patients with advanced colorectal cancer.
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
authors.forename: Miriam
authors.initials: M
authors.lastname: Koopman
authors.affiliation: Netherlands Cancer Institute (NKI), Biometrics Department, Amsterdam, Netherlands.
authors.forename: Ninja F
authors.initials: NF
authors.lastname: Antonini
authors.affiliation: Rijnstate Hospital, Arnhem, Netherlands.
authors.forename: Joep
authors.initials: J
authors.lastname: Douma
authors.affiliation: Atrium Medical Centre, Heerlen, Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Wals
authors.affiliation: Isala Hospital, Zwolle, Netherlands.
authors.forename: Aafke H
authors.initials: AH
authors.lastname: Honkoop
authors.affiliation: Maasland Hospital, Sittard, Netherlands.
authors.forename: Frans Lg
authors.initials: FL
authors.lastname: Erdkamp
authors.affiliation: Martini Hospital, Groningen, Netherlands.
authors.forename: Robert S
authors.initials: RS
authors.lastname: de Jong
authors.affiliation: Meander Medical Centre, Amersfoort, Netherlands.
authors.forename: Cees J
authors.initials: CJ
authors.lastname: Rodenburg
authors.affiliation: Maxima Medical Centre, Veldhoven, Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Vreugdenhil
authors.affiliation: Amphia Hospital, Breda, Netherlands.
authors.forename: Olaf Jl
authors.initials: OJ
authors.lastname: Loosveld
authors.affiliation: Zaans Medical Centre, Zaandam, Netherlands.
authors.forename: Aart
authors.initials: A
authors.lastname: van Bochove
authors.affiliation: Jeroen Bosch Hospital, Den Bosch, Netherlands.
authors.forename: Harm Am
authors.initials: HA
authors.lastname: Sinnige
authors.affiliation: Catharina Hospital, Eindhoven, Netherlands.
authors.forename: Geert-Jan M
authors.initials: GM
authors.lastname: Creemers
authors.affiliation: Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Margot Et
authors.initials: ME
authors.lastname: Tesselaar
authors.affiliation: St Antonius Hospital, Nieuwegein, Netherlands.
authors.forename: Peter H Th J
authors.initials: PHTJ
authors.lastname: Slee
authors.affiliation: Viecuri Hospital, Venlo, Netherlands.
authors.forename: Marjon Jbp
authors.initials: MJ
authors.lastname: Werter
authors.affiliation: Comprehensive Cancer Centre East (IKO), Nijmegen.
authors.forename: Linda
authors.initials: L
authors.lastname: Mol
authors.affiliation: Netherlands Cancer Institute (NKI), Biometrics Department, Amsterdam, Netherlands.
authors.forename: Otilia
authors.initials: O
authors.lastname: Dalesio
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. Electronic address: c.punt@onco.umcn.nl.
authors.forename: Cornelis Ja
authors.initials: CJ
authors.lastname: Punt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D015996:Survival Rate
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin