Comparison of clinical trials with finasteride and dutasteride

Abstract

Finasteride selectively inhibits the Type 2 isoenzyme of 5alpha-reductase (5AR) (the enzyme responsible for converting testosterone to dihydrotestosterone [DHT]) whereas dutasteride inhibits both Type 1 and Type 2 5AR. General conclusions regarding the differences and similarities of these 2 agents, in terms of pharmacologic effect, safety, and efficacy, can be drawn from evaluation of short-term comparative trials and similar but non-comparative long-term trials. Dutasteride therapy reduces serum DHT significantly more than does finasteride. In men with benign prostatic hyperplasia (BPH), treatment with either agent results in similar prostate gland volume reduction, flow rate and symptom improvement, and similar reductions in long-term risk of BPH development in terms of symptom progression and acute urinary retention (AUR) and BPH-related surgery. There does not appear to be any clinically significant difference between the adverse event profiles of dutasteride and finasteride. Although weak evidence suggests a difference in the onset of clinical benefit, the available non-comparative trial data do not confirm this finding. Patients with symptomatic BPH who receive dutasteride or finasteride, either as monotherapy or combination therapy with alpha-blockers, can expect to experience significant prostate gland size reduction, improved symptoms, and reduced risk of progression in terms of long-term adverse outcomes.

Figure 1

The 2 5α-reductase inhibitors (5ARIs), dutasteride and finasteride, suppress dihydrotestosterone (DHT) by inhibiting the conversion of testosterone to DHT. Finasteride inhibits only the Type 2 5AR isoenzyme, whereas dutasteride, the only dual 5ARI, selectively inhibits both Type 1 and Type 2 5AR isoenzymes. Data from Bartsch G et al.

Figure 2

A comparative phase II evaluation of dutasteride and finasteride in a double-blind placebo-controlled trial clearly demonstrates that serum dihydrotestosterone (DHT) suppression is significantly greater with dutasteride (0.5 mg daily) than with finasteride (5 mg daily). Data from Clark RV et al.

Figure 3

A 3-month prospective study was conducted to evaluate the onset of symptom relief in patients treated with dutasteride (n = 120) vs those treated with finasteride (n = 120). One hundred and twenty men with symptomatic benign prostatic hyperplasia (BPH) were treated with dutasteride for 3 months followed by an additional 120 men treated consecutively with finasteride for 3 months. Data from Hagerty JA et al.

Figure 4

These figures compare the 4-year PLESS finasteride results with the 2-year pivotal dutasteride results. The vertical line in the PLESS data graphs represents the 2-year time point for comparison purposes. (A) symptoms, (B) prostate volume, (C) surgery, (D) acute urinary retention. PLESS, Proscar Long-Term Efficacy and Safety Study; AUA-SI, American Urological Association-Symptom Index; BPH, benign prostatic hyperplasia; TPV, total prostate volume; AUR, acute urinary retention. Reprinted from Roehrborn CG et al. with permission form Elsevier and McConnell JD et al. Copyright © 1998 Massachusetts Medical Society. All rights reserved.

Figure 5

Long-term prostate volume changes (A) and symptom improvement (B) between dutasteride and finasteride can be determined by evaluating changes from baseline in long-term non-comparative trials. As these are not comparative data, patient populations from the various studies may differ. Dutasteride data for 1, 2, and 4 years are shown in yellow. Continuing improvement in symptoms over the 4 years is seen. Finasteride data for 1, 4, and 5 years are shown in orange, including those from PLESS and MTOPS. DB, double-blind; OL, open-label; PLESS, Proscar Long-Term Efficacy and Safety Study; MTOPS, Medical Treatment of Prostate Symptoms Study; AUA, American Urological Association; SI, AUA Symptom Index. Data from Roehrborn et al,, and McConnell JD et al.,