Review of dutasteride/tamsulosin fixed-dose combination for the treatment of benign prostatic hyperplasia: efficacy, safety, and patient acceptability

Abstract

Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) will usually affect older men, of whom 50% over the age 60 years and almost 90% in their nineties will be bothered enough by their symptoms that they request some type of treatment. However, symptomatic bother may also affect men in their forties with a prevalence rate of almost 18%. The International Prostate Symptom Score (IPSS) has become the most widely used and best validated questionnaire to allow the patient to quantify the severity of his LUTS/BPH symptoms. This score has become the cornerstone in demonstrating the "rate of symptom response" for the patient who has been exposed to any type BPH management. Question 8 on the IPSS score is what is defined as the "Quality of Life" question or what is also termed the "Bothersome Index." The score out of 6 as declared by the patient will reflect the degree of concern that the patient is feeling about his symptoms and the reduction of the score after treatment is a statement of their improved quality of life. There are 2 families of accepted medical therapy to treat the symptoms of BPH and potentially prevent the most worrisome long-term sequelae of progression of BPH: urinary retention or the need for surgery. When defining the impact of the main types of medical therapy, the alpha blockers have been termed the "openers" and the 5 alpha-reductase inhibitors are described as the "shrinkers." Since they each offer a different mechanism of effect, the concept of combination therapy was raised and trialed many times over recent years. The final aspect of any medical therapy is the patient's satisfaction with the treatment and the side effects. In the CombAT (Combination of Avodart and Tamsulosin) trial a new assessment was developed and tested called the Patient's Perception of Study Medication (PPSM) which told the investigators if the patients, given free choice, would choose to take that combination of medication to treat their problem and stay on the medication.

Keywords: 5 alpha reductase inhibitors; BII; Benign Prostatic Hyperplasia Impact Index; Patient’s Perception of Study Medication; alpha blockers; benign prostatic hyperplasia; combination therapy; lower urinary tract symptoms; quality of life.

Figure 1

Risk factors for benign prostatic hyperplasia progression.– Abbreviations: IPSS, International Prostate Symptom Score; PSA, prostate-specific antigen.

Figure 2

Milestones of changes in medical management of benign prostatic hyperplasia (BPH).

Figure 3

Comparison of baseline demographics and study designs of MTOPS and CombAT. Abbreviations: AUR, acute urinary retention; BPH, benign prostatic hyperplasia; IPSS, International Prostate Symptom Score; PV, prostate volume; PSA, prostate-specific antigen. Note: Reprinted with permission from Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57(1):123–131. Copyright © 2010 Elsevier.

Figure 4

Mean change International Prostate Symptom Score (IPSS) from baseline: primary endpoint in 4-year CombAT trial. Note: Reprinted with permission from Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57(1):123–131. Copyright © 2010 Elsevier.

Figure 5

Four-year primary and secondary CombAT endpoints. Abbreviations: AUR, acute urinary retention; BPH, benign prostatic hyperplasia; IPSS, International Prostate Symptom Score; UTI, urinary tract infection.

Figure 6

CombAT 4-year composite primary endpoint – time to first AUR or BPH surgery. Note: Reprinted with permission from Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57(1):123–131. Copyright © 2010 Elsevier. Abbreviations: AUR, acute urinary retention; BPH, benign prostatic hyperplasia; CI, confidence interval; RRR, relative risk reduction.

Figure 7

CombAT 4-year secondary endpoints – clinical progression. Notes: Rate based on ITT population; *P < 0.001 versus combination. Reprinted with permission from Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57(1):123–131. Copyright © 2010 Elsevier. Abbreviations: AUR, acute urinary retention; BPH, benign prostatic hyperplasia; IPSS, International Prostate Symptom Score; ITT, intention-to-treat; UTI, urinary tract infection.

Figure 8

Description of Patient’s Perception of Study Medicine Questionnaire (PPSM). Note: Seven-point scale (Qs 1 to 11) or ‘yes’, ‘no’ or ‘not sure’ (Q12).

Figure 9

Patient’s Perception of Study Medicine Questionnaire (PPSM) results for questions 11 and 12.

Figure 10

CombAT 4-year incidence of drug-related adverse events. Note: Reprinted with permission from Roehrborn CG, Siami P, Barkin J, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57(1):123–131. Copyright © 2010 Elsevier.