Selenium fails to protect NSCLC patients against second primary tumors

By Lynda Williams, Senior medwireNews Reporter

Selenium supplementation does not reduce the risk for second primary tumors (SPTs) in patients with resected non–small-cell lung cancer (NSCLC), researchers say.

As reported in the Journal of Clinical Oncology, 1561 patients without mediastinal node disease after surgery for stage I NSCLC were randomly assigned to receive selenized yeast (200 µg/day) or placebo for 48 months.

Although selenium supplementation was well tolerated, with no increased risk for diabetes or skin cancer, the 2009 interim analysis performed when 46% of the projected endpoints of SPTs had occurred found no significant difference in the risk for SPTs between the treatment groups.

Indeed, there was a trend toward a lower rate of SPTs in the placebo-treated group, resulting in the recommendation that the trial be halted, report Fadlo Khuri (Winship Cancer Institute of Emory University, Atlanta, Georgia) and co-authors.

At the follow-up analysis in 2011, 252 SPTs in 224 patients had occurred, translating to 54% of projected endpoints. Lung SPTs were detected in selenium-treated and placebo-treated patients at comparable rates of 3.54 and 3.39 cases per 100 person–years, respectively, with overall rates of SPTs of 1.62 and 1.30 per 100 person–years, respectively.

The 5-year survival rate was also comparable, at 74.4% for those given selenium and 79.6% for controls.

Of note, the risk for recurrent NSCLC or an SPT significantly differed between active smokers, former smokers, and never-smokers, at rates of 30%, 24%, and 20%, respectively, among patients assigned to take selenium.

A similar pattern was also found for overall survival, with 3-year and 5-year rates of 85.5% and 74.9%, respectively, for patients who continued to smoke at least until the past year, versus 90.0% and 83.6% for never-smokers.

The team also compared disease-free survival (DFS) by the patients’ baseline selenium levels. Patients with low, average, and high selenium concentrations who were given selenium supplements had 5-year DFS rates of 75.5%, 75.6%, and 72.9%, respectively. This compared with 72.9%, 78.2%, and 80.9%, respectively, for the control groups.

“This study was not powered to evaluate the interaction between selenium level and treatment; however, the descriptive data suggest that any beneficial effect of selenium is limited to patients with a low baseline selenium level,” Khuri et al say.

“It is now clear that there is no demonstrable benefit in giving supplements such as selenium… to current smokers,” they write. “However, the data suggest that a better approach might be to treat never-smokers with low serum selenium levels.”

The team concludes: “In the current era of molecularly targeted therapies for lung cancer, it seems that persisting with broad approaches in genomically unselected patient populations who continue to smoke is highly unlikely to be successful.”

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