title: Impact of Pre-Treatment Lactate Dehydrogenase Levels on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer.
abstract: BACKGROUND
  To investigate the impact of pre-treatment lactate dehydrogenase (LDH) levels on the outcome of patients with metastatic colorectal cancer treated with first-line chemotherapy with or without the anti-VEGF monoclonal antibody, bevacizumab, in a phase III prospective multicentre randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial.
  
  
  METHODS
  Three hundred and seventy patients enrolled onto the ITACa first-line trial were considered for this study, 176 receiving chemotherapy (either FOLFIRI or FOLFOX) plus bevacizumab and 194 receiving chemotherapy only. Pre-treatment LDH levels were evaluated to identify a potential correlation with progression-free survival (PFS), overall survival (OS) and objective response rate.
  
  
  RESULTS
  Information on pre-treatment LDH levels was available for 344 patients. High LDH levels were predictive of a lower median PFS (8.1 months vs. 9.2 months, p< 0.0001) and median OS (16.1 months vs. 25.2 months, p< 0.0001) in the overall population. In the chemotherapy plus bevacizumab group, median PFS was 9.1 and 9.8 months in patients with high LDH and low LDH, respectively (p= 0.073), whereas in the chemotherapy-only arm it was 6.9 and 9.1 months, respectively (p < 0.0001). In patients with high LDH, the addition of bevacizumab to chemotherapy led to a reduction in the rate of progressive disease (16.4 vs. 30.5%, p= 0.081) and to a prolonged PFS (p= 0.028).
  
  
  CONCLUSIONS
  A high LDH value was confirmed as a marker of poor prognosis. Bevacizumab reduced the progressive disease rate and improved PFS in the high-LDH subgroup, making serum LDH a potentially effective an easily available and marker to select patients who benefit from bevacizumab.
  
  
  BACKGROUND
  NCT01878422 ClinicalTrials.gov.
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Passardi
authors.affiliation: Unit of Biostatistics and Clinical Trials, IRST IRCCS, Meldola, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.affiliation: Oncology Unit, Degli Infermi Hospital, Faenza, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Tamberi
authors.affiliation: Medical Oncology Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cavanna
authors.affiliation: Department of Oncology, Per gli Infermi Hospital, Rimini, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Tassinari
authors.affiliation: Oncology Unit, University Hospital Modena, Modena, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Fontana
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Pini
authors.affiliation: Medical Oncology Unit, Ramazzini Hospital, Carpi, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bernardini
authors.affiliation: Medical Oncology Unit, Vito Fazzi Hospital, Lecce, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Accettura
authors.affiliation: Biosciences Laboratory, IRST IRCCS, Meldola, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ulivi
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Frassineti
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D045022:Lactate Dehydrogenases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D012007:Rectum / Q000187:drug effects* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab; D045022:Lactate Dehydrogenases