title: Analysis for prognostic factors of 60-day mortality: evaluation of an irinotecan-based phase III trial performed in the first-line treatment of metastatic colorectal cancer.
abstract: BACKGROUND
  Mortality rates in published irinotecan-based trials range between 1.7% and 5.0%. This analysis aimed to evaluate clinical and histopathologic factors associated with 60-day mortality in first-line therapy for metastatic colorectal cancer (mCRC).
  
  
  METHODS
  Sixty-day all-cause and disease-specific mortality rates from 479 patients who participated in a randomized phase III study comparing FUFIRI (5-fluorouracil [5-FU], leucovorin, irinotecan) (n = 238) vs. mIROX (modified irinotecan plus oxaliplatin (n = 241) were evaluated for association with prognostic factors such as platelet counts, alkaline phosphatase (AP) levels, white blood cell (WBC) counts, hemoglobin values, lactate dehydrogenase (LDH) levels, carcinoembryonic antigen (CEA) levels, and several other baseline parameters using univariate and multivariate logistic regression analyses applied to patients combined from both treatment groups.
  
  
  RESULTS
  The all-cause 60-day mortality rate was 5.0% (24/479). Thirteen patients (5.5%) in the FUFIRI arm died within the first 60 days of treatment compared with 11 (4.6%) patients in the mIROX arm (P = .68). Among the 24 patients in both treatment arms, mortality was qualified as disease related in 15 (63%) patients and treatment related in 7 (29%) patients (P = .695). In multivariate analyses, high LDH levels (P = .010) and an elevated WBC count (P = .006) remained as significant independent prognostic factors. Low Karnofsky performance status (KPS) showed a strong trend but failed to reach statistical significance (P = .057) as did AP levels and the number of metastatic sites.
  
  
  CONCLUSIONS
  In this study 63% of the early deaths were disease related, whereas only 29% were possibly related to study medication. Independent prognostic factors for early mortality were LDH levels and WBC counts. KPS showed a strong trend in the multivariate analysis. Future investigation may consider LDH levels and WBC counts for exclusion criteria.
authors: Department of Medical Oncology, Klinikum Grosshadern, University of Munich, Munich, Germany. clemens.giessen@med.uni-muenchen.de
authors: Clemens
authors: C
authors: Giessen
authors: Sebastian
authors: S
authors: Stintzing
authors: Ruediger Paul
authors: RP
authors: Laubender
authors: Donna Pauler
authors: DP
authors: Ankerst
authors: Christoph
authors: C
authors: Schulz
authors: Nicolas
authors: N
authors: Moosmann
authors: Dominik Paul
authors: DP
authors: Modest
authors: Andreas
authors: A
authors: Schalhorn
authors: Ludwig Fischer
authors: LF
authors: von Weikersthal
authors: Volker
authors: V
authors: Heinemann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin