Correlation of lactate dehydrogenase isoenzyme profile with outcome in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab or cediranib: Retrospective analysis of the HORIZON i study

Jair Bar*, Stuart Spencer, Shethah Morgan, Laura Brooks, David Cunningham, Jane Robertson, Juliane M. Jürgensmeier, Glenwood D. Goss

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction Bevacizumab improves outcome for patients with advanced colorectal cancer (CRC) when added to chemotherapy. The HORIZON I trial resulted in similar outcome with bevacizumab or cediranib, a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptor, as treatment of advanced CRC. The spectrum of lactate dehydrogenase (LDH) isoenzyme expression was examined in serum samples of HORIZON I participants to identify biomarkers predictive of efficacy of VEGF pathway inhibitors. Materials and Methods Total LDH levels, as well as LDH isoenzyme levels in frozen baseline serum samples, were retrospectively evaluated. Total LDH serum levels measured during the study, progression-free survival (PFS), and overall survival (OS) were available from the HORIZON I study data. Results Total LDH levels measured in the frozen serum samples correlated with those measured in fresh samples. The expected reciprocal correlation was found between hypoxic and oxic LDH isoenzymes. High total LDH correlated with shorter PFS, and high hypoxia-related LDH isoenzymes correlated with shorter PFS and OS. The difference in outcome of the cediranib-treated patients vs. those treated with bevacizumab was not substantially different in the various LDH isoform expression subgroups. In patients with a hypoxic LDH pattern of expression, there was a nonsignificant trend of better outcome in cediranib-treated patients. Conclusion Evaluation of total LDH and its isoforms in frozen serum samples is feasible. High total LDH and high hypoxic LDH isoenzymes were associated with poor prognosis. Further studies are needed to evaluate the predictive value of LDH isoenzyme expression pattern for VEGF-pathway inhibition efficacy.

Original languageEnglish
Pages (from-to)46-53
Number of pages8
JournalClinical Colorectal Cancer
Volume13
Issue number1
DOIs
StatePublished - Mar 2014
Externally publishedYes

Funding

FundersFunder number
Royal Marsden National Institute for Health Research
AstraZeneca
NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
National Institute for Health Research

    Keywords

    • Angiogenesis inhibitors
    • FOLFOX regimen
    • Hypoxia
    • LDH
    • Predictive biomarkers

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