title: Primary tumor location and bevacizumab effectiveness in patients with metastatic colorectal cancer.
abstract: BACKGROUND
  There is an unmet need for predictive markers for the antiangiogenic agent bevacizumab in metastatic colorectal cancer (mCRC). We aimed to assess whether the location of the primary tumor is associated with bevacizumab effectiveness when combined with capecitabine and oxaliplatin (CAPEOX) in the first-line treatment of patients with mCRC.
  
  
  METHODS
  A cohort of 667 consecutive patients with mCRC from the general community treated from 2006 to 2011 with CAPEOX and bevacizumab as standard first-line therapy was compared with a cohort of 213 patients treated with CAPEOX from 2003 to 2006, before bevacizumab was approved. Main outcome measures were progression-free survival (PFS) and overall survival (OS). Differences in outcome were tested using Kaplan-Meier curves and log-rank tests, and multivariate analyses were carried out using Cox Proportional Hazards models.
  
  
  RESULTS
  Patients treated with CAPEOX and bevacizumab with primary tumors originating in the sigmoid colon and rectum had a significantly better outcome than patients with primary tumors originating from the cecum to the descending colon, both for PFS (median PFS 9.3 versus 7.2 months; hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.56-0.82) and for OS (median OS 23.5 versus 13.0 months; HR 0.47, 95% CI 0.38-0.57). This difference was confirmed in multivariate analyses after adjustment for other potentially prognostic factors. For patients treated with CAPEOX, there was no association between primary tumor location and outcome, neither in unadjusted nor adjusted analyses.
  
  
  CONCLUSIONS
  The addition of bevacizumab to CAPEOX in first-line treatment of patients with mCRC may primarily benefit patients with primary tumors originating in the rectum and sigmoid colon. This hypothesis needs to be validated in data from completed randomized trials.
  NCT00212615.
authors.affiliation: Department of Oncology;. Electronic address: mogens.karsboel.boisen@regionh.dk.
authors.forename: M K
authors.initials: MK
authors.lastname: Boisen
authors.affiliation: Department of Oncology;; Department of Medicine, Herlev Hospital, Copenhagen University Hospital, Herlev.
authors.forename: J S
authors.initials: JS
authors.lastname: Johansen
authors.affiliation: Department of Statistics, Bioinformatics and Registry, Danish Cancer Society, Copenhagen.
authors.forename: C
authors.initials: C
authors.lastname: Dehlendorff
authors.affiliation: Department of Oncology, Roskilde Sygehus, Roskilde.
authors.forename: J S
authors.initials: JS
authors.lastname: Larsen
authors.affiliation: Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Østerlind
authors.affiliation: Department of Oncology, Västerås County Hospital, Västerås, Sweden;; Department of Oncology, Aalborg Sygehus, Aalborg.
authors.forename: J
authors.initials: J
authors.lastname: Hansen
authors.affiliation: Department of Oncology and Palliation, Hillerød Hospital, Hillerød.
authors.forename: S E
authors.initials: SE
authors.lastname: Nielsen
authors.affiliation: Department of Oncology, Odense University Hospital, Odense.
authors.forename: P
authors.initials: P
authors.lastname: Pfeiffer
authors.affiliation: Department of Oncology, Odense University Hospital, Odense.
authors.forename: L S
authors.initials: LS
authors.lastname: Tarpgaard
authors.affiliation: Department of Oncology and Hematology, Næstved Sygehus, Næstved.
authors.forename: N H
authors.initials: NH
authors.lastname: Holländer
authors.affiliation: Department of Oncology, Herning Hospital, Herning.
authors.forename: N
authors.initials: N
authors.lastname: Keldsen
authors.affiliation: Department of Oncology, Vejle Sygehus, Vejle.
authors.forename: T F
authors.initials: TF
authors.lastname: Hansen
authors.affiliation: Department of Oncology, Sydvestjysk Sygehus, Esbjerg, Denmark.
authors.forename: B B
authors.initials: BB
authors.lastname: Jensen
authors.affiliation: Department of Oncology.
authors.forename: B V
authors.initials: BV
authors.lastname: Jensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000378:metabolism; D000069287:Capecitabine; D002432:Cecum / Q000473:pathology; D044683:Colon, Descending / Q000473:pathology; D012809:Colon, Sigmoid / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000401:mortality; D012007:Rectum / Q000473:pathology; D012811:Sigmoid Neoplasms / Q000188:drug therapy / Q000401:mortality; D013534:Survival; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil
keywords: bevacizumab; biomarker; chemotherapy; metastatic colorectal cancer; primary tumor