Lung Cancer.pdf

Prevention and Early Detection of Lung Cancer 265
berger and Frost first proposed selenium’s role in cancer prevention in 1969.
Since then, further research in animal studies has shown that selenium compounds
can inhibit and retard carcinogenesis at higher dose levels.
While studies have shown that high levels of natural selenium are associated
with significant hepatotoxic effects—a finding that has limited research
efforts—synthetic organoselenium compounds have been reported
to be effective and less toxic chemopreventive agents in laboratory animals.
The synthetic compound 1,4-phenylenebis(methylene)selenocyanate
is one of several synthetic compounds that have shown efficacy in inhibiting
lung tumors in laboratory animals.
A major clinical trial by Clark and colleagues attempted to determine
whether a nutritional supplement of selenium would decrease the incidence
of basal cell and squamous cell carcinomas of the skin (Clark et al,
1996). This multicenter, double-blind, randomized trial evaluated 1,312
patients aged 18 to 80 years who had a history of skin cancer. Patients
were given 200 g of selenium (in the form of a 0.5-g high-selenium
brewer’s dried yeast tablet) or placebo daily. Although selenium had no
effect on skin cancer incidence, secondary end point analyses revealed
that selenium supplementation was associated with a significantly lower
incidence of nonskin cancer and with lower nonskin and overall cancer
mortality rates. In addition, rates of lung cancer, prostate cancer, and
colon cancer were all significantly reduced in patients in the selenium
arm.
Other studies, however, have produced conflicting evidence regarding
the benefit of selenium supplementation in preventing cancer. From the
epidemiologic data, it is unclear whether selenium acts alone or as part of
a combination of antioxidants.
These observations have led to an intergroup trial to study selenium in
lung cancer. This randomized trial was launched in 2000 and is studying
the effects of supplemental selenium in preventing second primary tumors
in patients with stage I NSCLC (T1N0M0 and T2N0M0). The target
accrual is more than 2,000 patients. It is hoped that this study will define a
possible role for selenium in lung cancer chemoprevention.
Further drug development and large prospective clinical trials are necessary
to confirm selenium’s role in the chemoprevention of lung cancer.
Only then can public health recommendations regarding selenium supplementation
be made.
Lipoxygenase Inhibitors
Eicosanoids, which are formed when lipoxygenases combine with arachidonic
acid, are thought to play a role in tumor promotion, tumor progression,
and metastatic disease. The eicosanoids include prostaglandins,
leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acids (HETEs).
Studies of cancer cells show that lipoxygenase inhibitors, which combine
with lipoxygenase and thereby prevent its substrate-enzyme combi-