By Louis Kuritzky, MD , Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.
Androgen Deprivation Therapy for Localized Prostate Cancer
After skin cancer, prostate cancer (P-CA) is the most common cancer among American men. Guidelines suggest that for localized P-CA (stage T1 or T2) surgery, radiation, or conservative management (treatment deferred until demanded by disease progression) is appropriate. Despite the absence of major consensus group endorsement, androgen deprivation therapy (ADT) has been sufficiently popular that in a 2003 report, ADT was employed second only to surgery for localized disease.
When employed as an adjunct to radiation or surgery in high-risk P-CA (poorly differentiated or advanced stage), ADT has been associated with as much as 50% or greater mortality reductions.
Lu-Yao et al evaluated data on men aged 66 years or greater (n=19,271) treated with either ADT or conservative management only (ie, no definitive surgical or radiation therapy had been used). The population studied began accruing data in 1992, and men were followed through 2006.
ADT did not show advantage compared to conservative management for either mortality specifically related to P-CA or all-cause mortality. In fact, for the metric of 10-year prostate cancer-specific mortality, ADT was associated with a statistically significant 17% increased hazard ratio. Selecting the subgroup of men with poorly differentiated P-CA did not favorably affect overall mortality either, although in this subgroup there was a favorable impact on P-CA related mortality. Despite its recent popularity, ADT for localized disease has no mortality advantage over conservative management strategies.
Lu-Yao GL, et al. AMA. 2008;300(2):173-181.
Heart Failure Complicated by Atrial Fibrillation: Rate or Rhythm Control?
Among patients with atrial fibrillation (AFIB), clinical trial data have confirmed that outcomes using rate control are as favorable as using rhythm control. Since rate control is usually easier to attain, and medications for rate control are generally both less expensive and better tolerated than agents required for rhythm control, rate control is often the preferred strategy.
Patients with heart failure (CHF) who also have AFIB have a worse prognosis. Whether management of AFIB in heart failure is most advantageous with rate or rhythm control has not been fully elucidated, since the trial data upon which rate/rhythm equivalence is based were sparsely populated with heart failure patients.
Roy et al performed a randomized trial of rate vs rhythm control in heart failure patients with AFIB (n=1,376). Patients were followed for approximately 3 years. At the end of this trial, both mortality and all secondary outcomes were essentially equivalent with either intervention, although there was a trend towards greater CV mortality in the rhythm control group. Additionally, rhythm control patients experienced more hospitalizations.
Based upon these results, the authors suggest that rate control is preferred. Because pharmacologic treatments were used rather than radioablation techniques, no conclusions can be drawn about the relative efficacy of the latter.
Roy D, et al. N Engl J Med. 2008;358(25):266-277.
Pregabalin for Diabetic Peripheral Neuropathic Pain
Long-standing diabetes is associated with development of diabetic peripheral neuropathy (DPN). As many as 1 out of every 4 patients with diabetes eventually develops diabetic peripheral neuropathic pain (DPNP). In addition to the burden of pain, patients are often much disquieted by the worsening of DPNP symptoms at night which interrupts sleep and produces next-day excessive drowsiness, as well as exacerbation of pain with activity which may compromise well-intended exercise plans.
Pregabalin is one of two agents approved for the treatment of DPNP in the last 2 years. Because our experience with pregabalin is relatively recent, this report which includes data from 7 randomized trials (total n= 1,510) may help bolster our knowledge base.
Daily pregabalin doses ranging from 150 mg-600 mg were all shown to be more effective than placebo when divided t.i.d.; when administered b.i.d., only a 600 mg daily dose was effective.
The literature has shown that patients with chronic pain report that a 30% reduction in pain from baseline is a clinically meaningful improvement.
Adverse eventsmost commonly dizziness, edema, weight gain, and somnolence are dose related. Less than 10% of patients discontinue treatment for any of these individual adverse events.
Freeman R, et al. Diabetes Care. 2008;31(7):1448-1454.