title: Prognostic factors for 60-day mortality in first-line treatment of metastatic colorectal cancer (mCRC): individual patient analysis of four randomised, controlled trials by the AIO colorectal cancer study group.
abstract: BACKGROUND
  The 60 day mortality is an established parameter for chemotherapy-related safety in randomised trials for metastatic colorectal cancer (mCRC). Prognostic factors associated with 60-day mortality would be helpful to identify high-risk patients in advance.
  
  
  METHODS
  Individual baseline patient data from four randomised, controlled trials from the Arbeitsgemeinschaft Internistische Onkologie (AIO) study group were retrospectively analysed. Chemotherapy consisted of fluoropyrimidine (5-FU/capecitabine), irinotecan, oxaliplatin with or without bevacizumab or cetuximab. Prognostic factors were identified by univariate and multivariate logistic regression models in two cohorts: one limited to ECOG PS 0 and 1 and one including ECOG PS 2 patients.
  
  
  RESULTS
  A total of 1377 patients were evaluated. The analysis of ECOG PS 0, 1 and 2 patients consisted of 898 patients where a total of 33 deaths within the first 60 days of treatment (3.7%) occurred. In multivariate analysis, 60-day mortality was significantly associated with ECOG PS 2 and high leucocyte count (white blood cell, WBC). Odds ratio was 6.28 for WBC and 12.92 for ECOG PS 2. Exclusion of ECOG PS 2 patients but inclusion of one trial limited to ECOG PS 0 and 1 patients resulted in 1302 assessable patients and 44 early deaths (3.4%). In both cohorts, around 50% of deaths were disease related. WBC was confirmed as a significant risk factor for early death (OR 7.60). A combined score using ECOG PS 2 and WBC ≥8.000/µl is able to identify high-risk patients with a sensitivity of 18% and specificity of 98%.
  
  
  CONCLUSIONS
  In this large retrospective analysis of individual patient data, around 50% of early deaths were disease related. Elevated WBC was found strongly associated with increased 60-day mortality in first-line treatment of mCRC. The proposed AIO-60-Day-Mortality score serves as an additional trial exclusion criterion.
authors.affiliation: Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Munich.
authors.forename: C
authors.initials: C
authors.lastname: Giessen
authors.forename: U
authors.initials: U
authors.lastname: Graeven
authors.forename: R P
authors.initials: RP
authors.lastname: Laubender
authors.forename: D P
authors.initials: DP
authors.lastname: Modest
authors.forename: C
authors.initials: C
authors.lastname: Schulz
authors.forename: R
authors.initials: R
authors.lastname: Porschen
authors.forename: W
authors.initials: W
authors.lastname: Schmiegel
authors.forename: A
authors.initials: A
authors.lastname: Reinacher-Schick
authors.forename: S
authors.initials: S
authors.lastname: Hegewisch-Becker
authors.forename: S
authors.initials: S
authors.lastname: Stintzing
authors.forename: V
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D000068258:Bevacizumab; D000069287:Capecitabine; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D012372:ROC Curve; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000068818:Cetuximab; D005472:Fluorouracil
keywords: 60-day mortality; first-line chemotherapy; metastatic colorectal cancer; prognostic factors; randomised trials