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Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin.

Publication ,  Journal Article
Armstrong, AJ; George, DJ; Halabi, S
Published in: J Clin Oncol
September 20, 2012

PURPOSE: Lactate dehydrogenase (LDH) is an enzyme involved in anaerobic glycolysis and regulated by the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR)-containing complex 1 (PI3K/Akt/TORC1) pathway as well as tumor hypoxia/necrosis. High serum LDH levels are associated with poor prognosis in patients with cancer, including renal cell carcinoma (RCC). We tested whether serum LDH is prognostic and has predictive value in patients with metastatic RCC receiving an mTOR inhibitor. PATIENTS AND METHODS: We evaluated pretreatment and post-treatment serum LDH in 404 poor-risk patients with RCC treated with the TORC1 inhibitor temsirolimus or interferon alfa in an international phase III randomized trial. The proportional hazards model was used to test for the prognostic and predictive association of LDH in predicting overall survival (OS). RESULTS: Mean baseline serum normalized LDH was 1.23 times the upper limit of normal (ULN; range, 0.05 to 28.5 × ULN). The multivariable hazard ratio for death was 2.81 (95% CI, 2.01 to 3.94; P < .001) for patients with LDH more than 1 × ULN versus patients with LDH ≤ 1 × ULN. The LDH-treatment interaction term was statistically significant for OS (P = .016). Among 140 patients with LDH above the ULN, OS was significantly improved with temsirolimus (6.9 v 4.2 months; P < .002). Among 264 patients with normal LDH, OS was not significantly improved with temsirolimus as compared with interferon therapy (11.7 v 10.4 months; P = .514). CONCLUSION: Serum LDH is a prognostic and a predictive biomarker for the survival benefit conferred by TORC1 inhibition in poor-risk RCC. Further investigation of the predictive role of LDH as a measure of benefit with PI3K/TORC1 pathway inhibition in other RCC risk groups and other tumor types is warranted.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

September 20, 2012

Volume

30

Issue

27

Start / End Page

3402 / 3407

Location

United States

Related Subject Headings

  • Transcription Factors
  • TOR Serine-Threonine Kinases
  • Survival Analysis
  • Sirolimus
  • Retrospective Studies
  • Protein Kinase Inhibitors
  • Prognosis
  • Predictive Value of Tests
  • Oncology & Carcinogenesis
  • Multivariate Analysis
 

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Armstrong, A. J., George, D. J., & Halabi, S. (2012). Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin. J Clin Oncol, 30(27), 3402–3407. https://doi.org/10.1200/JCO.2011.40.9631
Armstrong, Andrew J., Daniel J. George, and Susan Halabi. “Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin.J Clin Oncol 30, no. 27 (September 20, 2012): 3402–7. https://doi.org/10.1200/JCO.2011.40.9631.
Armstrong, Andrew J., et al. “Serum lactate dehydrogenase predicts for overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin.J Clin Oncol, vol. 30, no. 27, Sept. 2012, pp. 3402–07. Pubmed, doi:10.1200/JCO.2011.40.9631.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

September 20, 2012

Volume

30

Issue

27

Start / End Page

3402 / 3407

Location

United States

Related Subject Headings

  • Transcription Factors
  • TOR Serine-Threonine Kinases
  • Survival Analysis
  • Sirolimus
  • Retrospective Studies
  • Protein Kinase Inhibitors
  • Prognosis
  • Predictive Value of Tests
  • Oncology & Carcinogenesis
  • Multivariate Analysis