By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.
Cancer Risks Associated with Diagnostic X-rays
Source: Linet MS, et al. CA Cancer J Clin 2012;62:75-100.
Within a few years after the initiation of diagnostic X-rays, toxic effects were noted, including increased risk for skin cancer, leukemia, dermatitis, and cataracts. In this early period, doses of X-ray, especially from fluoroscopy, were high. Protective devices for patients as well as persons occupationally exposed to diagnostic radiation demonstrably reduced such adverse consequences.
The dose of radiation that is required to induce cancer is not clearly known. However, populations who have been exposed to calculable levels of radiation through wartime exposure (i.e., Japanese atomic bomb survivors) and subjects receiving radiation therapy help us to predict a dose-response relationship. It is not yet clear to what extent the high-dose radiation exposure and subsequent development of cancer reflects cumulative lower dose exposures. Nonetheless, because radiation toxicity may be related to total exposure, peak exposure, or both, radiation from commonly used diagnostic procedures has stimulated concern.
For instance, a CT of the abdomen, commonly used investigationally for persons with acute or chronic abdominal pain, incurs the same amount of radiation exposure as 750 chest X-rays. Linet et al quote recent estimates suggesting that the 70 million CT scans performed each year in the United States could lead to 29,000 additional cancers.
The authors recommend a number of steps to reduce unnecessary radiation exposure, including 1) learning about radiation doses associated with various imaging techniques, 2) consideration of imaging without radiation (i.e., ultrasound, MRI), and 3) avoidance of elective X-rays in pregnant women.
The REDEEM Trial: Dutasteride for Management of Localized Prostate Cancer
Source: Fleshner NE, et al. Lancet 2012; 379:1103-1111.
Prostate cancer (PCA) comprises 25% of all newly diagnosed cancers in men in the United States. PCA chemoprevention trials with 5-alpha-reductase inhibitors have had mixed results. The first major PCA prevention trial with finasteride showed a 25% decrease in total PCA vs placebo, but an increase in more aggressive (high Gleason score) cancers. A similarly designed large prevention trial with dutasteride again found a 25% decrease in total PCA, but there was an increase in more aggressive cancers (albeit not statistically significant in this trial). Based on these mixed results, clinicians have been reluctant to use 5-alpha-reductase inhibition for PCA prevention.
Might 5-alpha-reductase inhibitors prove more useful for treatment of PCA rather than prevention? The REDEEM trial randomized men with localized PCA (n = 300) who had elected active surveillance for their disease to dutasteride 0.5 mg/d or placebo. At 3 years time, the risk of PCA progression was reduced by 38% in men on dutasteride.
Because dutasteride is generally well tolerated, men with non-aggressive Gleason scores (six or less) who might otherwise select active surveillance for localized disease may have reduced risk of disease progression with the addition of dutasteride.
Amantadine for Traumatic Brain Injury
Source: Giacino JT, et al. N Engl J Med 2012;366:819-826.
In young adults (age 15-30), traumatic brain injury (TBI) is the most common cause of death and disability. As many as one in seven TBI hospital admissions leaves the hospital in a vegetative state. Amantadine (AMT) has achieved some popularity for inclusion in pharmacotherapy regimens for disorders of consciousness, although the mechanism by which AMT effects positive change is uncertain. Certainly it has been shown that AMT blocks N-methyl-D-aspartate, and is an indirect agonist of dopamine, but what these pharmacologic effects do to enhance outcomes is unclear. In any case, initial trials have supported its use, and a major observational trial indicated better outcomes in TBI for persons who had received AMT.
Patients who had sustained TBI (n = 184) and who were either vegetative or minimally conscious for at least 1 month (and no longer than 16 weeks) after injury were randomized to AMT or placebo. AMT was administered initially at 100 mg b.i.d., and titrated to 200 mg b.i.d. if the Disability Rating Scale had not shown improvement. The course of treatment was 4 weeks in duration, and patients were monitored for 2 weeks after discontinuation of treatment.
AMT treatment was associated with statistically significantly better functional recovery outcomes than placebo. AMT is not a new medication, so its adverse effects profile, characterized by mild, transient adversities, is well known. These data support the inclusion of AMT in the pharmacologic regimen of serious TBI.