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

Alessandro Passardi, Emanuela Scarpi, Stefano Tamberi, Luigi Cavanna, Davide Tassinari, Annalisa Fontana, Sara Pini, Ilaria Bernardini, Caterina Accettura, Paola Ulivi, Giovanni Luca Frassineti, Dino Amadori, Alessandro Passardi, Emanuela Scarpi, Stefano Tamberi, Luigi Cavanna, Davide Tassinari, Annalisa Fontana, Sara Pini, Ilaria Bernardini, Caterina Accettura, Paola Ulivi, Giovanni Luca Frassineti, Dino Amadori

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Consort flowchart.
Fig 1. Consort flowchart.
Fig 2. PFS and OS according to…
Fig 2. PFS and OS according to LDH.
Fig 3. PFS and OS according to…
Fig 3. PFS and OS according to LDH in CT+B and CT only arms.
Fig 4. PFS and OS according to…
Fig 4. PFS and OS according to treatment as a function of LDH.

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Source: PubMed

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