| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Guest Access | Sign In via User Name/Password
|
|
|
|||||||
Guest Access | Sign In via User Name/Password |
|||||||||
Tampa, FL
Correspondence to: Gerold Bepler, MD, PhD, Division of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, MRC-4W, Room 4046, Tampa, FL 33612; e-mail: gerold.bepler{at}moffitt.org
Lung cancer is the second-most-common cancer diagnosis in men and women.1 It accounts for more deaths than prostate, breast, and colon cancer combined. Many risk factors for lung cancer have been identified. Smoking is the most prominent and modifiable risk factor. Still, 10 to 15% of lung cancers occur in those who are lifetime neversmokers (a person who has smoked < 100 cigarettes during lifetime) and 55 to 65% in those that have quit smoking. Many treatment modalities including chemotherapy, radiation, and surgery are now available for lung cancer therapy; however, the survival rates for the 60 to 70% of patients who present with advanced disease remain dismal.
To reduce the incidence of lung cancer, focus has turned to chemoprevention: the use of agents to reduce, prevent, or reverse carcinogenesis.2 Agents explored to date have been ineffective, and in the case of beta-carotene have even shown harmful effects. Multiple in vitro and epidemiologic studies had suggested a chemopreventative effect for beta-carotene on lung carcinogenesis. However, once tested under rigorous prospective conditions in randomized phase III trials,34 beta-carotene was associated with an increased lung cancer risk rather than the hypothesized decreased risk. This speaks to the importance of evaluating agents in a randomized prospective fashion as the "gold standard" for proof of efficacy (ie, a reduction in cancer incidence).
Statins have become a cornerstone in the treatment of patients with atherosclerotic disease, since their use has resulted in improvements in outcome. In addition to their lipid-lowering effects through inhibition of hydroxy-methylglutaryl coenzyme A reductase, statins have antitumor effects in vitro. They have been demonstrated to increase apoptosis,5 suppress angiogenesis through their effects on vascular endothelial growth factor,6 and alter invasion and metastatic potential through interaction with adhesion molecules.6 In addition, epidemiologic data have shown an association between the use of statins and a decrease in cancer incidence.78
However, data also exist against the use of statins for the chemoprevention of cancer. To clarify these findings, large metaanalyses have been published. Dale et al9 published a metaanalysis evaluating 26 randomized controlled trials of statins. They found no beneficial or detrimental effect of statins in relation to overall cancer risk or cancer death, a result echoed by another metaanalysis10 of 35 randomized controlled trials.
The study by Khurana et al11 in this issue of CHEST (see page 1282) is a retrospective case-control study that evaluated the potential impact of statins on the development of lung cancer in > 400,000 patients seen in Department of Veterans Administration hospitals. Lung cancer was diagnosed in approximately 7,300 of these patients (1.5%), and statin use > 6 months was associated with a 55% reduction in lung cancer risk (p < 0.01). This benefit was observed even after controlling for age, history of tobacco use, and race.
These results are encouraging and strengthen the hypothesis that statins may be useful for lung cancer chemoprevention. However, as pointed out by the authors,11 the study has weaknesses innate to its design. Firstly, it is a retrospective analysis of mainly male veterans, and thus only partially representative of the diverse population of the United States. In particular, the impact of statins on lung cancer risk in women cannot sufficiently be addressed. Secondly, the interaction between tobacco and statin use can only be marginally investigated in the data set because of uncertainties in data accuracy. Other exposures to chemicals, radiation, and potentially carcinogenic substances were not explored in depth. Statins were obviously used in this population for specific clinical indications, thus limiting the observation to patients with specific medical conditions. Finally, aside from the lung cancer risk reduction, patients with a < 6-month use of statins had an increased risk of lung cancer, which raises the question of a potential tumor promoting effect of statins.
Many questions remain regarding the application of statins for chemoprevention of lung cancer. Does the dose of statins play a role in its effect? What about treatment duration? Is one statin superior to another? Perhaps the lung cancer risk reduction in this population is a result of other lifestyle changes, for instance diet and exercise, and not etiologically related to statin use? To answer these and other questions, prospective data need to be obtained in controlled clinical trials, possibly with surrogate biomarkers as the primary end point initially to minimize time, cost, and sample size of such studies. At present, statins should be utilized based on the strict guidelines of the Adult Treatment Panel III12 until data from randomized controlled phase III trials with lung cancer incidence and/or mortality as primary end point become available.
Footnotes
Dr. Gray is a Hematology/Oncology Fellow, Dr. Alberts is Professor of Medicine and Oncology, and Dr. Bepler is Professor of Medicine and Oncology, Division of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute.
The authors have no conflicts of interest to disclose.
References
Related Article
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
