Trial Information

First-line FOLFIRI and Bevacizumab in Patients With Advanced Colorectal Cancer Prospectively Stratified According to Serum LDH

The VEGF-driven tumour pathway has been demonstrated to represent a novel therapeutic target
for an innovative class of antineoplastic agents. Among these antiangiogenetic-targeted
treatment modalities the anti-VEGF monoclonal antibody bevacizumab has become a new standard
of care for first-line treatment of metastatic colorectal cancer. The biological link
between hypoxia, LDH levels and the tumour-driven angiogenesis pathway through the abnormal
activation of the hypoxia Inducible factor 1 α (HIF1-α) is well established. HIF1-α is a key
transcription factor that up-regulates a series of genes involved in glycolytic metabolism,
angiogenesis, cell survival and erythropoiesis Accordingly to this biological assumption
Azuma et al (Azuma et al 2007) demonstrated that high LDH serum levels were associated with
tumour over-expression of VEGFA and VEGFR-1. As a clinical consequence it has been
speculated that LDH levels may represent an indirect indicator of activated tumour
angiogenesis and ultimately of worse prognosis We previously analysed the role of LDH
pre-treatment serum levels in colorectal cancer patients receiving first-line bevacizumab in
metastatic colorectal cancer treated with first-line bevacizumab were eligible. A control
group including all consecutive patients treated with chemotherapy alone was also
considered. Pre-treatment LDH serum levels were collected for all cases