Selenium Does Not Benefit -- and May Harm -- Most Patients With NSCLC

Nick Mulcahy

June 05, 2010

June 5, 2010 (Chicago, Illinois) — The vast majority of lung cancer patients do not benefit from selenium, according to the results of a major study presented here at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting.

In fact, the mineral, which is a common ingredient in vitamin supplements and acts as an antioxidant, might cause harm in current and former smokers with lung cancer.

In the trial of 1561 patients with early-stage nonsmall-cell lung cancer (NSCLC), study participants underwent resection before being randomized to daily selenium or placebo for 4 years.

Dr. Daniel Karp

The investigators found 1.36 cases of a second primary lung tumor per 100 person-years among patients taking placebo, and 1.91 cases among selenium users (P = .15); the difference was not statistically significant and therefore could have been due to chance.

Although it is not entirely clear if selenium caused harm, there was definitely no evidence of benefit, said the study's lead author.

What we can say for sure is that selenium was not beneficial.

"What we can say for sure is that selenium was not beneficial," said Daniel Karp, MD, professor of thoracic/head and neck medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

"In the presence of tobacco carcinogens, antioxidants may do harm," postulated Dr. Karp about the possibility that selenium causes a worse outcome. He was referring to an earlier study with another antioxidant, beta carotene, which suggested a worsening of lung cancer with the use of that supplement (N Engl J Med. 1994;330:1029-1035).

Dr. Karp pointed out that there was an exception to the otherwise negative findings for selenium in the NSCLC patients.

A small subset of lung cancer patients seemed to benefit from selenium — those who had never smoked (n = 94), said Dr. Karp.

Among never-smokers, the 5-year overall survival rate was 87% for selenium users and 83% for placebo recipients, said Dr. Karp. However, the difference was not statistically significant and therefore the benefit was not proven.

What Should a Clinician Recommend?

Another lung cancer expert at the ASCO meeting suggested that the study's results raise a question: What should clinicians tell former and current smokers with lung cancer about multivitamin use?

I will not tell my patients to avoid selenium or a multivitamin.

"The slight increase in secondary lung cancers among selenium users in the study was not statistically significant. As a result, I will not tell my patients to avoid selenium or a multivitamin," said Gregory Masters, MD, a medical oncologist at the Helen F. Graham Cancer Center in Newark, Delaware.

"But I will tell patients that there is no benefit with supplemental selenium," he told Medscape Oncology.

Dr. Karp agreed, and said "we have to be cautious" about concluding anything beyond the fact that selenium did not have a proven benefit among users in the study.

However, Dr. Karp said that this trial and others, such as the beta-carotene study, might require a "rethinking" of the recommendations for multivitamin use by lung cancer patients.

Also, he said that if selenium has a potential benefit in some patients with lung cancer, "we need to find those people in need of supplementation."

Most of the patients in the trial started with a "normal selenium level," said Dr. Karp, referring to an 80 to 130 ng/mL blood level. This is in contrast to research from China, which indicates that selenium deficiency is common there, he pointed out.

In people with normal levels of the mineral, taking supplemental selenium is akin to a car having too many tires — it is not necessary and will impair optimal functioning, Dr. Karp explained.

Early Research Suggested Benefit

The new trial, led by the Eastern Cooperative Oncology Group (ECOG) and conducted between 2000 and 2009, was a "confirmatory" trial, said Dr. Karp.

Dr. Mark Kris

A previous skin cancer trial (JAMA.1996;276:1957-1963) found, as a secondary observation, that selenium use was associated with "about a 30% reduction in lung cancer," Dr. Karp explained.

"There had been strong suggestive evidence that selenium could decrease the risk of a second primary lung tumor," said Dr. Karp about earlier research.

Despite the negative outcome in the ECOG study, the trial was not bad news for patients with lung cancer, suggested Mark G. Kris, MD, chief of the Thoracic Oncology Service at Memorial Sloan-Kettering Cancer Center in New York City.

The good news is that we saw 80% long-term survival.

"The good news is that we saw 80% long-term survival," noted Dr. Kris, who moderated a press conference that included a review of the selenium findings. He is incoming chair of ASCO's Cancer Communications Committee.

At 5 years, the selenium group had an 80% survival rate, compared with 75% for the placebo group (P = .15).

Dr. Kris reminded members of the media at the ASCO press conference that an important part of the clinical strategy with lung cancer patients is to "get them to stop smoking." Stopping smoking has been shown to improve outcomes in patients already diagnosed with lung cancer, as reported by Medscape Oncology.

Trial Details

The primary outcome of the ECOG trial was the development of a second primary lung cancer. Approximately 1% to 2% of early-stage NSCLC patients develop a second primary cancer in the first year after surgery, and the chance of developing another new lung cancer rises by approximately 2% each year, said Dr. Kris.

In the study, patients with resected stage IA and IB NSCLC were randomly assigned to receive 200 μg of selenium daily or placebo for 4 years. Patients had to be cancer-free for at least 6 months after surgery to participate. Twice as many participants received selenium as placebo, and all were to be followed for 10 years.

The study was halted early, after a median follow-up of more than 4 years, when it became clear "that the result would not revert to a positive outcome" said Dr. Karp.

The investigators found that 5-year progression-free survival was 78% in the placebo group and 72% in the selenium group. They also found that 216 patients developed a second primary cancer, including 84 (38.9%) lung cancer tumors.

Dr. Karp reports receiving research funding from Pfizer. Dr. Masters has disclosed no relevant financial relationships. Dr. Kris reports serving in a consultant or advisory role for AstraZeneca, Boehringer, Ingelheim, GlaxoSmithKline, Merck, Novartis, and Pfizer.

American Society of Clinical Oncology (ASCO) 2010 Annual Meeting: Abstract CRA7004. Presented June 5, 2010.

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