Elevated levels of an enzyme already considered a risk factor for aggressive renal cell carcinoma (RCC) may also indicate how well an inhibitor of the mammalian target of rapamycin (mTOR) protein can combat this disease in a given patient.
High serum levels of lactate dehydrogenase (LDH) are associated with poor prognosis in persons with RCC or other types of cancer. The enzyme, which is found in almost all body tissues, plays a role in converting food to energy. Dying or injured cells release LDH, so elevated levels of the enzyme as reflected in blood tests are used to identify cancer, tissue damage, and other disorders.
In RCC, elevated LDH levels signal tumor progression. Additionally, recent research has suggested that elevated LDH may also indicate the activation of key genetic alterations that lead to cancer proliferation. One such cancer gene pathway relies on the mTOR protein.
A team led by Andrew J. Armstrong, MD, ScM, of the Duke Cancer Institute at Duke University Medical Center in Durham, North Carolina, tested whether serum LDH is prognostic and has predictive value in patients with metastatic RCC who are receiving an mTOR inhibitor. The investigators evaluated pretreatment and posttreatment serum LDH in 404 poor-risk patients with RCC who had been treated with either the standard therapy of interferon-alpha or the mTOR inhibitor temsirolimus.
Patients with high LDH levels at baseline survived significantly longer on the mTOR inhibitor therapy than on interferon-alpha (median survival 6.9 months vs 4.2 months, respectively). At the 6-month mark, 53.7% of the temsirolimus users with high LDH levels were alive, compared with 39.5% of the interferon-alpha users with high LDH levels. At 12 months, survival rates were 34.3% in the temsirolimus group and 12.7% in the interferon-alpha group.
In patients with normal LDH levels, overall survival did not significantly improve with temsirolimus therapy compared with interferon-alpha therapy (median survival 11.7 months vs 10.4 months, respectively).
These results led Armstrong and colleagues to conclude in Journal of Clinical Oncology that serum LDH is a prognostic and predictive biomarker for the survival benefit conferred by mTOR inhibition in poor-risk RC, although they noted that more studies are needed to verify the findings.