Impact of Pre-Treatment Lactate Dehydrogenase Levels on Prognosis and Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer

PLoS One. 2015 Aug 5;10(8):e0134732. doi: 10.1371/journal.pone.0134732. eCollection 2015.

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).

Conclusion: 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.

Trial registration: NCT01878422 ClinicalTrials.gov.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / therapeutic use*
  • Bevacizumab / therapeutic use*
  • Colon / drug effects*
  • Colon / pathology
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Lactate Dehydrogenases / blood*
  • Male
  • Middle Aged
  • Neoplasm Metastasis / diagnosis
  • Neoplasm Metastasis / drug therapy*
  • Neoplasm Metastasis / pathology
  • Prognosis
  • Rectum / drug effects*
  • Rectum / pathology
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Bevacizumab
  • Lactate Dehydrogenases

Associated data

  • ClinicalTrials.gov/NCT01878422

Grants and funding

This trial was partially supported by the Italian Medicines Agency (AIFA - research grant no. FARM6FJJAY). AIFA was involved in the design of the clinical study but not in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to submit the article for publication. No other funding or sources of support to be declared.