Outlook: Clinical Trials

Pharmacy Times, November 2011 Cough & Cold, Volume 77, Issue 11

USPSTF Evidence Update: Prostate Cancer Screening

The US Preventive Services Task Force (USPSTF) recently updated evidence reviews on screening and treatments for prostate cancer. 1 The USPSTF reviewed randomized trials of prostatespecific antigen (PSA)—based screening, randomized trials and cohort studies of prostatectomy or radiation therapy versus watchful waiting, and large observational studies of perioperative harms.

Results of the review showed that of 5 screening trials, the 2 largest and highest quality studies reported conflicting results. One trial demonstrated that screening correlated with reduced prostate cancer—specific mortality compared with no screening after 9 years in men aged 55 to 69 years. However, the other large screening trial found that there was no statistically significant effect after 10 years.

Additionally, a review of 26 treatment trials was performed. One trial found that prostatectomy for localized prostate cancer decreased risk for prostate cancer— specific mortality compared with watchful waiting through 13 years of follow-up; however, benefits appeared limited to men younger than 65 years. The treatment trials also showed that treating men with prostatectomy or radiation therapy instead of watchful waiting may result in erectile dysfunction and/or urinary incontinence. Other complications of prostatectomy included perioperative death (about 0.5%) and cardiovascular events (0.6% to 3%), and radiation therapy was associated with bowel dysfunction.

The USPSTF concluded that PSA-based screening results in small or no reduction in prostate cancer—specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary.

Vitamin E Supplementation Increased Prostate Cancer Risk

A dditional insight has been provided from the follow-up analysis of the Selenium and Vitamin E Cancer Prevention Trial (SELECT).1 The primary analysis included 34,887 men who were randomly assigned to 1 of 4 treatment groups: selenium (n = 8752), vitamin E (n = 8737), both agents (n = 8702), and placebo (n = 8696). Initial results found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a statistically nonsignificant increase in prostate cancer risk with vitamin E.

The report includes 54,464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Results showed that 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% CI, 1.004-1.36; P = .008) compared with 529 men in the placebo group. Additionally, 575 men in the selenium group developed prostate cancer (HR, 1.09; 99% CI, 0.93-1.27; P = .18) and 555 in the selenium plus vitamin E group developed prostate cancer (HR, 1.05; 99% CI, 0.89-1.22; P = .46).

The absolute increase in risk of prostate cancer per 1000 personyears was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination compared with placebo. Investigators concluded from the follow-up data that dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.

Saw Palmetto: No Benefit in Reducing Lower Urinary Tract Symptoms of BPH

A clinical study was conducted to assess the effect of saw palmetto extract at up to 3 times the standard dose on lower urinary tract symptoms attributed to benign prostatic hyperplasia (BPH). 3 This double-blind, multicenter, placebo-controlled, randomized trial evaluated men (n = 369) 45 years or older with a peak urinary flow rate of at least 4 mL/s and an American Urological Association Symptom Index (AUASI) score of between 8 and 24 at 2 screening visits. Study subjects received 1, 2, and then 3 doses (320 mg/day) of saw palmetto extract or placebo, with dose increases at 24 and 48 weeks. The primary outcome was difference in AUASI score between baseline and 72 weeks.

Results showed that mean AUASI scores decreased from 14.42 to 12.22 points (-2.20 points; 95% CI, -3.04 to -0.36) with saw palmetto extract and from 14.69 to 11.70 points (-2.99 points; 95% CI, -3.81 to -2.17) with placebo. Investigators concluded that increasing doses of saw palmetto extract did not reduce lower urinary tract symptoms of BPH more than placebo. PT

Cognitive Behavior Therapy for Childhood OCD

A recent randomized, controlled, multicenter clinical trial evaluated the efficacy of augmenting serotonin reuptake inhibitors (SRIs) with cognitive behavior therapy (CBT) or a brief form of CBT, defined as instructions in CBT delivered in the context of medication management, in children with obsessivecompulsive disorder (OCD). 4

Subjects aged 7 to 17 years (n = 124) were randomly assigned to 1 of 3 treatment strategies that included 7 sessions over 12 weeks: 42 received medication management only, 42 received medication management plus CBT, and 42 received medication management plus instructions in CBT. The primary outcome was improvement in baseline obsessive-compulsive scale score by 30% or more and demonstration of a change in continuous scores over 12 weeks.

Results showed that 68.6% (95% confidence interval [CI], 53.9%- 83.3%) in the plus CBT group were considered responders, which was significantly better than the 34.0% (95% CI, 18.0%-50.0%) in the plus instructions in CBT group, and 30.0% (95% CI, 14.9%- 45.1%) in the medication management only group. Investigators concluded that among patients aged 7 to 17 years with OCD and partial response to SRI use, the addition of CBT to medication management compared with medication management alone resulted in a significantly greater response rate.

Dr. Reed received her doctor of pharmacy degree from the University of the Sciences in Philadelphia, Pennsylvania, and currently works as a medical editor in the greater Philadelphia area.


1. Chou R, Croswell JM, Dana T, et al. Screening for prostate cancer: a review of the evidence for the U.S. preventive services task force [published online ahead of print October 7, 2011]. Ann Intern Med.

2. Franklin ME, Sapyta J, Freeman JB, et al. Cognitive behavior therapy augmentation of pharmacotherapy in pediatric obsessive-compulsive disorder: the Pediatric OCD Treatment Study II (POTS II) randomized controlled trial. JAMA. 2011;306(11):1224-1232.

3. Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549-1556.

4. Barry MJ, Meleth S, Lee JY, et al. Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial. JAMA. 2011;306(12):1344-1351.