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PURPOSE: The Colorectal Oral Novel therapy For the Inhibition of angiogenesis and Retarding of Metastases (CONFIRM)-randomized trials, investigating the role of the VEGF-receptor inhibitor PTK787/ZK 222584 (vatalanib) in colorectal cancer (FOLFOX 4 ± vatalanib), showed some benefit in patients with high serum lactate dehydrogenase (LDH) levels. Here, we investigated the expression of LDH5 (encoded entirely by the LDHA gene, regulated by the hypoxia inducible factors) in cancer tissues from patients recruited in the CONFIRM trials and relationship to response. EXPERIMENTAL DESIGN: Paraffin-embedded materials from 179 patients recruited in the CONFIRM trials were analyzed by immunohistochemistry for the expression of the LDH5 protein. Correlations with serum LDH, response, and survival were assessed. RESULTS: A significant association of tumor burden and of poor performance status (PS) with serum LDH was noted. Poor PS and high tumor LDH5 expression predicted for poor response rates. High tissue LDH5 was related to poor progression-free survival (PFS) only in the placebo group of patients, whereas the addition of vatalanib seemed to improved response and PFS in this subgroup. High serum LDH levels were linked with significantly poorer overall survival, which however was not sustained in multivariate analysis. CONCLUSIONS: Serum LDH and tissue LDH5 levels are complementary features that help to characterize the activity of LDH in colorectal cancer and have a potent value in predicting response to chemotherapy. The addition of vatalanib diminished the impact of LDH expression on the prognosis of patients.

Original publication

DOI

10.1158/1078-0432.CCR-10-2918

Type

Journal article

Journal

Clin cancer res

Publication Date

15/07/2011

Volume

17

Pages

4892 - 4900

Keywords

Adult, Aged, Aged, 80 and over, Angiogenesis Inhibitors, Colorectal Neoplasms, Female, Gene Expression Regulation, Neoplastic, Humans, Isoenzymes, Kaplan-Meier Estimate, L-Lactate Dehydrogenase, Lactate Dehydrogenases, Male, Middle Aged, Phthalazines, Prognosis, Pyridines, Treatment Outcome, Tumor Burden