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New biomarker found for kidney cancer

Common enzyme could predict response to treatment

Jo Carlowe

Tuesday, 14 August 2012

A common enzyme that is easily detected in blood may predict how well patients with advanced kidney cancer will respond to a specific treatment.

The finding, published this week in the Journal of Clinical Oncology, could lead to the first blood test to determine the best treatment for late-stage kidney cancer.

"Being able to direct these patients to a treatment we know will help them would be a major advancement in their care," said Andrew Armstrong, associate professor of medicine and surgery at Duke Cancer Institute in North Carolina, and lead author of the study.

"At the same time, patients who would not benefit from the treatment would be spared from undergoing a drug regimen with potential side effects that could diminish their quality of life."

Armstrong and colleagues focused on an enzyme known as lactate dehydrogenase, or LDH, which is found in almost all body tissues and plays a role in converting food to energy. As cells die or are injured, they release LDH, so elevated levels of the enzyme have long been used in blood tests to identify cancer, tissue damage, and other disorders.

In kidney cancer, elevated LDH levels have been considered a risk factor for aggressive disease, signalling tumour progression. More recent studies have suggested that elevated LDH may also indicate the activation of key genetic alterations that lead to cancer proliferation. One of these cancer gene pathways relies on a protein called mammalian target of rapamycin, or mTOR, and drugs called mTOR inhibitors work to shut down the process.

An international Phase III trial testing an mTOR inhibitor known as temsirolimus found that the then-investigational drug extended the lives of patients with kidney cancer that had spread to other areas of the body, and it even helped the patients with high LDH levels who typically have a poor prognosis.

Intrigued by those results, the Duke researchers used data from the trial to determine whether a high LDH level was more than just a prognostic tool in advanced kidney cancer, and could perhaps also predict the effectiveness of an mTOR inhibitor.

Armstrong and colleagues analysed the outcomes of 404 of the study participants, approximately half of whom received a standard therapy, interferon-alpha, and half who received temsirolimus, which has since been approved by the U.S. Food and Drug Administration to treat kidney cancer. LDH levels had been measured at the start of the study for all participants.

In their analysis, the Duke team found that patients with high LDH levels at the start of the study survived significantly longer on the mTOR inhibitor drug than they did on interferon-alpha. Median survival for patients with high LDH levels was 6.9 months on temsirolimus compared to 4.2 months for the high LDH level patients on the standard drug. At six months, 53.7% of high LDH level patients taking temsirolimus were alive, compared to 39.5% taking interferon-alpha. Patient survival rates at 12 months were 34.3% for temsirolimus, vs. 12.7% for interferon-alpha.

Patients with low LDH at the start of the study showed little difference in survival based on the drug they received, with median survival of 11.7 months for the mTOR inhibitor patients compared to 10.4 months for those taking interferon-alpha.

"This is an exciting finding," Armstrong said. "In breast cancer, for example, we can test for HER-2 expression and offer effective treatments based on that. Having a similar biomarker for kidney cancer that could direct patients to the best therapies for their cancer would be a major step forward."

Armstrong said additional studies are needed to verify the finding, and to determine whether LDH might predict the success of additional drugs that target other cancers.

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