Kocatepe Tip Dergisi (2002),2, 119-130 The Medical Journal ofKocatepe • 2002, Afyon Kocatepe Oniversitesi RESULTS OF SWITCHING TERAZOSIN AND DOXAZOSIN IN THE TREATMENT OF BPH Murat SAM LI, Cetin DiN<;EL Afyon Kocatepe University. Faculty of Medicine. Department Of Urology. Afyon ABSTRACT:Objective: Medical treatment of the BPH is one of the alternatives among a variety of therapeutic options. Doxazosin and terazosin are the most widely used molecules in the treatment of BPH . We compared the effectivity of these molecules by switching the drug in those who did not benefit from the first drug. Methods: This was a prospective randomized study. Patients in the study were similar in age, prostatic weight, International Prostatic Symptom Score (I-PSS), uroflow parameters and PSA levels. Fifty men (mean age 59.4 years, SD 7.6, range 48-78) received either doxazosin (25 men), or terazosin (25 men), once daily at night. Patients were evaluated at one, 2 and 3 month s. Improvement in I-PSS and the maximal flow rate (Qmax) by minimum 20% was accepted as improvement. Patients who showed improvement in Hone of the parameters have switched the drug and these patients were followed in the next 3 months. Results: Of the 25 men using doxazosin, I I (44%) showed improve ment both in I-PSS and Qmax at 3 month s. Of the 25 men using terazosin, 10 (40%) showed improvement both in I-PSS and Qmax at 3 months (p>0.05). After 3 months of treatment, the peak urinary flow rate increas ed significantly (p< 0.001) for both doxazosin (+4.5 mLls) and terazosin (+3.1 mLls) groups. The International Prostatic Symptom Score improved significantly (P< 0.01) with both alpha-blockers after 3 month s of treatment in these groups. Nineteen patients, who did not show improve ment in any of the parameters, switched the drug. Of the patients who switched the drug, 2 (4%) showed improvement both in I-PSS and in the peak urinary flow rate, 2 (4%) showed improvement only in I-PSS but not in the peak urinary flow rate and 15 (30%) did not show improvement in any of the parameters. Conclusion: These results suggest that alpha blockade with either doxazosin or terazosin is effective in men with symptomatic BPH . Two of the alpha-blocking molecules showed equal effectivity in the treatment of BPH. If one of the molecules is ineffective in the treatment of BPH , then the other molecule will probably be ineffective. [Key Words: terazosin, doxazosin, benign prostatic hyperplasia, drug switch] INTRODUCTION In the I970s, the pioneering work of Caine led to the discovery of alpha-J­ Men over the age of 50 will probable have adrenoceptor predominance in the prostatic benign prostatic hyperplasia (BPH) at a rate of stroma and capsule. This finding triggered the about 85%. Also 50% of the men will require search for a-receptor blocking agents in treatment at their eighties [1]. Medical patients with lower urinary tract symptoms treatment of the BPH is one of the alternatives sugges tive of bladder outflow obstruction [2]. among a variety of therapeutic options. The initial agents were derived from Various types of surgery, medical treatment antihyper tensive drugs because of the a­ with alpha- l-u drenergic antagonists or 5-alpha­ receptor blocking capability [3]. Recently, reductase inhibitors are included in the options severa l investigations have detected of treatment. significantly more alpha- l-adre nergic receptors 119 in hypertrophic prostatic tissue than in normal agents are similar, this may not prove the tissue [4, 5, 6) and that blocking urethral alpha­ effectiveness of the agents are similar. We l- adrenoceptors causes the prostatic urethra to investigated whether one of the alpha- I­ relax [7). More recently, several prostate blockers is not effective; is it rational to expect ­, specific drugs have been introduced. During some improvement with another alpha- I­ II the last 2 decades, the therapeutic efficacy of blocker. these drugs has been clearl y demonstrated in f several clini cal trials, and today alpha- l ­ MATERIAL AND METHODS adrenocept or blockers are the first line medical treatment for lower urinary tract symptoms This is a two-armed, randomized study suggestive of bladder outlet obstruction [8). and lasted about 1,5 year. The pretrial The alpha- l -blockers are valued for rapid onset assess ment and establishing a baseline to of action, effectiveness independent of prostate evaluate the effect of treatment required each . size, minimal influence on sexual function and patient to undergo a history and symptom good therapeutic profile [9]. assessment, digital rectal examination (ORE), We searched the literature for doxazosin transrectal ultrasound (TRUS), and and terazosin switch or conversion protocols. uroflowmet ric analysis. The severi ty of One of the 2 studies we found in the literature symptoms was assesse d subjectively using the that investigated both drugs looked at which Intern ational Prostatic Symptom Score (I-PSS) dosage of each agent control blood pressure (maximum 35 points). Objective symptoms of [10]. This study also did not provide an BPH were evaluated by uroflowmetry [12]. appropriate conversion dosage for patients with Inclusion criteria of the study can be seen in benign prostatic hyperplasia. The other study Table (I ). Parameters of the patients enrolled in the literature reported the conversion of in the study are listed in Tabl e (2). Patients doxazosin to terazosin to determine whether were excluded if they had urinary tract the switch would lead to differences in BPH infection (> 10 white blood cell/hi gh power symptoms, blood pressure or adverse effects field), prostate cancer, had any other [II]. medication that would interfere with doxazosin In this study, we planned to investigate and terazosin or underwent prostatic surgery. 1­ whether different types of alpha-I-blockers PSS and quality of life scores (QOL score) may have different clini cal responses. However were evaluated by the same physician. the molecular structures of the alpha- I-blocker Table 1. Inclusi on criteria Parameter Value Qma x <15 mLis I-PSS score 28 PSA <4.0 ng/mL ORE No sign of malignancy TR US Any volume of prostate 120 Table 2. General parameters of the patients Age (yea rs) Prostate Vol. (mL) I-PSS score QOL score Qmax verage flow rate mean±S.D. 59,4±7,6 9, 1± 16,5 14,1±5,4 3,7±1,l min-max 14-83 8-28 2-6 Fifty patients with symptomatic BPH the treatment period was the maximum urinary study randomly assigned to terazosin (n = 25) or flow rates (Qmax). Improvement was defined 'al doxazosin (n = 25). Terazosin 10 mg and as a 20% decrease from baseline in I-PSS and doxazosin 8 mg once daily was administered 20% increase from baseline in Qmax. for 12 weeks. Symptoms were evaluated using Increasing QOL score by I point was detected, the International Prostate Symptom Sco re (I­ but it was not accepted as one of the PSS), and quality of life score (QOL) was improvement criteria (Table 3). Advers e assessed subjec tively before treatment , and reactions potentially related to the study drugs again after four, 8 and 12 weeks of treatment. were recorded throughout the treatment period. Objective measurement taken before and after Table 3. The criteria for evaluating treatment efficacy favorabl Parameter unfavorable e I-PSS score; after treatment to baseline ~20 % < 20% [(before treatment)-(after treatment)]/[before treatment] Qmax (mLlsec) ; after treatment to baseline ~20 % <20% [(after treatment)-(before treatment)]/[before treatment] The following protocol was used in drug evaluated every 4 weeks and reassessment was dose regimen; in the doxazosin group, patients employed with I-PSS, uroflowmetry and PSA started from 1mg and increased to 8mg, and in measurements. At the end of the 12 weeks of the terazosin group, patients started from 1mg treatment Qmax, I-PSS score were assessed and increased to 10mg. Patients switched whether to continue the drug or switch the drug doxazosin to terazosin or terazosin to with the other one. Ten patients on terazosin doxazosin with the following protocol; arm and nine patients on doxazosin arm did not doxazosin 8 mg to 10 mg terazosin, and 10 mg show improvement in I-PSS score and Qmax, terazosin to 8 mg doxazosin. so they had their drug switched with the other Treatment and follow-up flowchart was one after 2 weeks of washout period . These represented in Fig. (I). Twenty-five patients in patients were followed-up for more 3 months each arm of the treatment scheme were to evaluate effectiveness of the switched drug. randomized for the each drug. Patients were 121 BPH Symptoms IPSS Uroflowmelry n=50 TRUS,PSA,DRE no FOll OW-Up Medical lreatment n=25 n=25 Randomization for Doxazosin vs Terazosin Doxazosin; Terazosm: Evaluation at 1, 2, 3 mos. Evaluation at 1, 2, 3 mos. IPSS, Uroflow ., PSA IPSS, Uroflow., PSA artial Success With Drug yes yes n=11 n=10 (44%) (40%) cont. drug cont. drug n=9 n=10 no no (36%) (40%) Change Drug Doxazosin toTerazosin Terazosi n to Doxazosin n=10 n=9 .. Doxazosin; Terazosin; Evaluation at 1,2, 3 mos. Evaluation at 1, 2, 3 mos. IPSS, Uroflow.. PSA IPSS, Uroflow.. PSA artial Succe ss With 1 Drug n= l n=1 (11 %) (10%) yes yes n=7 (70%) n=8 (88%) no no Other Modes of Treatmen t Fig. 1. Treatment and follow-up scheme 122 Statistical Analysis improvement in Qmax value or I-PSS score (4 Changes in urodynamic parameters, I-PSS showed improvement in I-PSS and 1 in Qmax and QOL scores between baseline and, 3- and value in the doxazosin arm, and 3 showed 6-month follow-up were determin ed, and p improvement in I-PS S and 2 in Qmax value in values were calc ulated with the Wilcoxon the terazosin arm).