Pre-treatment lactate dehydrogenase levels as predictor of efficacy of first-line bevacizumab-based therapy in metastatic colorectal cancer patients

Abstract

Background:Lactate dehydrogenase (LDH) represents a predictive factor in colorectal cancer patients treated with the angiogenesis inhibitor PTK/ZK. We explored the role of pre-treatment LDH serum levels in colorectal cancer patients receiving first-line bevacizumab.Methods:Metastatic colorectal cancer treated with first-line bevacizumab was 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.Results:Median progression-free survival (PFS) in the control group for patients with high and low LDH levels was 4.2 and 8 months, respectively (P=0.0003). Median overall survival (OS) was 19.6 and 34.9 months for patients with high and low LDH levels, respectively (P=0.0014). In the bevacizumab group, partial responses were seen in 14 (58%) high-LDH and 8 (14%) low-LDH patients (P=0.0243), respectively, median PFS was 7.3 and 8.5 months, respectively (P=0.2), and median OS was 22 and 26.6 months, respectively (P=0.7).Conclusion:High LDH levels correlated with worse prognosis. Bevacizumab seemed capable of improving clinical outcome in this specific group of patients who usually present with an adverse natural history. The improved response rate also suggests a role for LDH as a predictive marker.

Relevance of CEA and LDH in relation to KRAS status in patients with unresectable colorectal liver metastases.

“…LDH is a metabolic enzyme that catalyzes the conversion of pyruvate to lactate under anaerobic conditions and is overproduced in cancer cells [8]. Several studies have demonstrated a negative association between elevated LDH and OS [9][10][11]. CEA is a glycoprotein involved in cell adhesion, immunity and apoptosis [12].…”

Lactate Dehydrogenase-5 (Ldh-5) Immunohistochemical Expression as Predictor of Efficacy of First-Line Therapy in Patients with Advanced Colorectal Cancer Treated with Chemotherapy and Bevacizumab

“…Similar results have been communicated in patients diagnosed of advanced Non-Small Cell Lung Cancer (NSCLC) [20], were a significantly poorer survival was noted in the group of patients with high LDH5 immunohistochemical reactivity, both when measured at cytoplasm and at nucleus. In addition, Scartozzi et al observed similar findings in patients with high LDH serum levels [21], who presented a significant shorter PFS (4.2 vs. 8 months, p=0.003) and OS (19.6 vs. 34.9 months, p=0.0014), when compared with patients with low LDH levels in serum. Despite all this data, in our series the high expression of LDH5 was not associated with classical clinical factors associated with worse prognostic features, such as loss of weight, bad performance status or more than one metastatic site.…”

“…Previous reports found similar results regarding to the better outcome of patients with overexpression of pro-angiogenic proteins when treated with Bevacizumab. Both patients with high levels of pKDR measured by immunohistochemistry, and patients with high serum level of LDH presented a benefit in RR, PFS and OS, when compared with patients with high expression of these markers and treated with chemotherapy alone [21,22]. All these experiences show that the addition of bevacizumab to chemotherapy permits to improve clinical outcome in a subgroup of patients who usually present with an adverse natural history.…”

Prognostic clinical factors in pretreated colorectal cancer patients receiving regorafenib: Implications for clinical management.

“…Accordingly with these observations we previously suggested that pre-treatment LDH levels may represent a relevant factor for the prediction of bevacizumab efficacy in an unselected population of CRC patients [13].…”