- Email: [email protected]
MP48-10 TADALAFIL ONCE A DAY SIGNIFICANTLY REDUCES PENILE LENGTH-LOSS IN PATIENTS POST BILATERAL NERVE-SPARING RADICAL PROSTATECTOMY (NSRP) - RESULTS FROM A RANDOMIZED CONTROLLED TRIAL
THE JOURNAL OF UROLOGYâ
e530
Vol. 191, No. 4S, Supplement, Monday, May 19, 2014
published clinical experience is limited. We report our experience with TTh in various categories of men with PCa. METHODS: A retrospective chart review identified 135 men (mean age 64 9y) with PCa who started TTh between May 2004 and Janurary 2013 and were followed for at least 6 months. Of these, 33 (24.4%) were on active surveillance (AS), 93 (68.9%) has undergone definitive local treatment for PCa and were without biochemical recurrence at the start of TTh, and 9 (6.7%) were treated with TTh after known biochemical recurrence. RESULTS: Of 33 men on AS, 3 men (9.1%) had upgrading on subsequent biopsy and 29 (87.9%) remained on AS over a mean follow-up of 31.2 mo. For 53 (39.3%) men starting TTh after radical prostatectomy, no patients had biochemical disease recurrence (PSA > 0.2ng/dL) over 30 mo of follow-up. Forty (29.6%) patients underwent either brachytherapy or XRT and were followed for an average of 26.7mo. Of these, 2(5%) patients developed PSA 2ng/dL over nadir but had subsequent PSAs below this threshold. Two (5%) men treated with radiotherapy elected for adjuvant HIFU. For the 9 (6.7%) patients with biochemically recurrent disease prior to starting T therapy, PSA continued to rise in 6 men without symptomatic metastatic disease over 28.7 months of follow-up. There were no skeletal-related events, and no deaths from prostate cancer in any group. Overall, 121 (89.6%) men with PCa remained on TTh with most men discontinuing therapy for lack of efficacy or other nononcologic reasons. CONCLUSIONS: TTh does not appear to cause higher than expected rates of PCa progression. A large majority of men with PCa treated with TTh will elect to continue treatment indefinitely. Source of Funding: none
MP48-09 TREATMENT OUTCOME OF CHEMICAL CASTRATION ON SEX OFFENDERS IN RELATION TO THE KINETICS OF SERUM TESTOSTERONE RECOVERY: IMPLICATIONS FOR DOSING SCHEDULE Kyo Chul Koo*, In Kyong Kim, Ho Chul Choi, Seung Hwan Lee, Sung Joon Hong, Byung Ha Chung, Seoul, Korea, Republic of INTRODUCTION AND OBJECTIVES: To evaluate outcomes of chemical castration on sexual offenders with a focus on the kinetics of serum testosterone (T) recovery. METHODS: This prospective analysis included 56 sex offenders imprisoned for sexual offenses. Thirty-eight and 18 patients who received 3 months and 6 months of leuprolide acetate injections were assigned to Group A and Group B, respectively. Psychobehavioral assessments and serum T levels were serially measured during the oncycle and the following observational 14-month off-cycle. RESULTS: Castrated levels of serum T reduced the frequency and intensity of sexual thoughts in 76% and 71% of Group A patients and in 78% and 72% of Group B patients, respectively. Reductions in masturbation frequency were observed in 74% of Group A and 83% of Group B patients. Wilson0 s Sex Fantasy Questionnaire (SFQ) scores also significantly reduced in both groups. In Group A, an upsurge of serum T to the flare-plateau level was observed during the first 2 months of the off-cycle, accompanied by an intense sexual drive and fantasy (Fig.1). In Group B, serum T gradually recovered to the baseline level and continued to upsurge beyond baseline levels during the observational period (Fig.2). SFQ scores of Group A returned to pre-treatment levels following the observational period; however, Wilson0 s SFQ scores of Group B remained suppressed. CONCLUSIONS: The efficacy of chemical castration varied according to the treatment duration. Regarding the kinetics of serum T recovery, maintaining at least 6 months of treatment warranted stable control of an excessive sexual drive following treatment cessation.
Source of Funding: none
MP48-10 TADALAFIL ONCE A DAY SIGNIFICANTLY REDUCES PENILE LENGTH-LOSS IN PATIENTS POST BILATERAL NERVE-SPARING RADICAL PROSTATECTOMY (NSRP) - RESULTS FROM A RANDOMIZED CONTROLLED TRIAL Gerald Brock*, London, Canada; Francesco Montorsi, Milan, Italy; Pierre Costa, Nîmes, France; Nimish Shah, Cambridge, United Kingdom; Jose Maria Martinez Jabaloyas, Valencia, Spain; Peter Hammerer, Braunschweig, Germany; Giuseppe M. Ludovico, Acquaviva delle Fonti, Bari, Italy; Carsten Henneges, Bad Homburg, Germany; Karim Hamidi, Neuilly Sur Seine, Germany; Andrea Rossi, €ttner, Bad Homburg, Germany; Sesto Fiorentino, Italy; Hartwig Bu John Mulhall, New York, NY INTRODUCTION AND OBJECTIVES: Secondary analyses on stretched penile length (SPL) data from a multicenter, randomized, double-blind, double-dummy, placebo (PLC) controlled clinical trial (NCT01026818) evaluating the efficacy of tadalafil (TAD) initiated postnsRP are reported. METHODS: Patients (pts) 68yrs with normal preoperative erectile function (EF) who underwent nsRP for localized prostate cancer (Gleason 7, PSA <10ng/mL) were randomized post nsRP 1:1:1 to 9month (mo) double-blind treatment (DBT) with TAD 5mg once a day (OaD), 20mg TAD on demand (pro re nata; PRN), or PLC, followed by 6-week drug-free washout (DFW)and 3mo open-label OaD treatment (OLT, all pts). Secondary outcome measures included change of SPL from baseline (nsRP) to end of 9mo DBT (eDBT)(LS mean change compared by prespecified ANCOVA, including terms for treatment, country, baseline, age, and Nerve Sparing Score [NSS]), responses to Sexual Encounter Profile Questions (SEP) 1 and 3 (mixed model for repeated measures including terms for treatment, country, visit, visittreatment interaction, age) and the Standardized Morning Erection Question (SMEQ; Cochrane Mantel Haenszel test adjusted for age and country).
THE JOURNAL OF UROLOGYâ
Vol. 191, No. 4S, Supplement, Monday, May 19, 2014
RESULTS: 423 pts were randomized to OaD (N¼139), PRN (N¼143), and PLC (N¼141); 114/122/155 completed 9mo DBT. Greater retained SPL was observed with OaD vs PLC at eDBT (Figure; LS mean [95%CI] difference OaD vs PLC, 4.1 [0.4, 7.8] mm, p¼0.032). No significant LS mean difference (p >0.05) was observed for PRN vs PLC. No significant effect of NSS on SPL loss was observed (Figure). Penile tumescense (SEP 1) as the initial sign of EF recovery was improved significantly vs. PLC at eDBT and OLT for pts randomized to OaD only. The ability for sexual intercourse (SEP 3) also significantly improved for pts on OaD vs placebo only at eDBT. The distribution of SMEQ responses was different at eDBT (p¼0.045), with 34.2% of pts on OaD, 50.0% on PRN and 56.5% on PLC reporting the absence of morning erections, At eDFW, SEP responses were not statistically significantly different between OaD and PLC. CONCLUSIONS: These data suggest that the early initiation of treatment with TAD OaD protects from penile length-loss and may contribute to protection from structural cavernosal changes post nsRP.
e531
significant improvements were observed in all endpoints, including successful intercourse attempts (SEP3) within approximately 15 minutes after dosing with both avanafil doses (P<.01 vs placebo; Table) and as early as 10 minutes post-dosing in the avanafil 200-mg group and 12 minutes post-dosing in the avanafil 100-mg group (P<.01 vs placebo). Common adverse events were headache, nasopharyngitis, and flushing. CONCLUSIONS: Avanafil had a significant erectogenic effect compared with placebo, including successful achievement of SEP2, SEP3, and changes in the IIEF-EF domain score. Furthermore, a significant number of sexual attempts were successful within approximately 15 minutes post-dosing. Table. Erectogenic Effects of Avanafil in Men With Mild to Severe ED During 8 Weeks of Treatment (ITT). Placebo
Avanfil 100 mg
Avanafil 200 mg
Successful Vaginal Penetration, SEP2 n LS Mean Percentage of Sexual Attempts (SE)
136
138
139
43.5 (3.2)
65.0 (3.2)*
65.4 (3.2)*
Successful Intercourse, SEP3 n LS Mean Percentage of Sexual Attempts (SE)
136
138
139
27.7 (3.3)
47.0 (3.3)*
48.7 (3.3)*
Successful Intercourse (SEP3) Within Approximately 15 Minutes Post-dosingz n LS Mean Percentage of Sexual Attempts (SE)
136
138
139
13.8 (2.9)
24.7 (2.9)y
28.2 (2.9)*
IIEF-EF Domain Score n LS Mean (SE)
Source of Funding: The study was funded by Eli Lilly and Company.
135
138
139
13.9 (0.8)
18.1 (0.8)*
19.1 (0.8)*
* P< .001 vs placebo; yP=.002 vs placebo; zAny erectogenic effect that had a stopwatch time of 17 minutes to include up to 17 minutes and 59 seconds could be considered to be within approximately 15 minutes. ITT, intent-to-treat population; LS, least squares; SE, standard error
Source of Funding: VIVUS, Inc.
MP48-11 TIME TO ERECTOGENIC EFFECT OF AVANAFIL IN A RANDOMIZED, PLACEBO-CONTROLLED TRIAL
MP48-12
Wayne J. G. Hellstrom*, New Orleans, LA; David Cook, Winston-Salem, NC; LeRoy Jones, San Antonio, TX; Charles H. Bowden, Wesley W. Day, Chien-Feng Chen, Mountain View, CA
EVALUATION OF NOCTURNAL TUMESCENCE AND ITS RESPONSE TO NIGHTLY SILDENAFIL CITRATE FOLLOWING RADICAL PROSTATECTOMY: A RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED STUDY
INTRODUCTION AND OBJECTIVES: Avanafil is a highly specific phosphodiesterase type 5 inhibitor approved for the treatment of erectile dysfunction (ED). This phase 4 study examined the efficacy and safety of avanafil approximately 15 minutes after dosing in men with mild to severe ED. METHODS: In this double-blind, 12-week (4-week run-in; 8-week treatment period) study, patients were randomized to placebo (n¼145), avanafil 100 mg (n¼147), or avanafil 200 mg (n¼148). Sexual function was assessed at baseline and at all follow-up visits using patient diaries and the International Index of Erectile Function (IIEF). The primary objective was to assess positive responses to Sexual Encounter Profile question 3 (SEP3) within approximately 15 minutes post-dosing. Patients were encouraged to attempt intercourse approximately 15 minutes post-dosing; stopwatches were used to measure timing of response. Other endpoints included the percentage of sexual attempts in which patients were able to insert the penis into the partner’s vagina (SEP2), percentage of successful sexual attempts in which patients maintained an erection of sufficient duration to have successful intercourse (SEP3), and change in the erectile function (EF) domain of IIEF. RESULTS: At baseline, mean age was 5810 years; 41% of patients had severe ED; mean duration of ED was 8970 months, and 60% had a history of sildenafil use. After 8 weeks of treatment,
Daniel Kim*, Dorota Hawksworth, Bethesda, MD; Judith Travis, Jennifer Cullen, Lauren Hurwitz, Rockville, MD; Stephen Brassell, Boise, ID; Inger Rosner, Bethesda, MD; Tom Lue, San Francisco, CA; Robert Dean, Bethesda, MD INTRODUCTION AND OBJECTIVES: Sildenafil citrate has been found efficacious therapy for post-prostatectomy impotence. In this study, we evaluated patterns of erectile function recovery following radical prostatectomy, and response to nightly therapy with Sildenafil citrate. METHODS: Ninety-four patients who underwent nerve sparing radical prostatectomy for localized prostate cancer were randomized to receive either a nightly 50mg dose of Sildenafil or placebo, starting on the first post-operative day and continuing for one year. Their erectile function was evaluated prior to surgery and at 2 weeks, 3, 6, 9, 12 and 13 months post-operatively. Both subjective, self-reported International Index of Erectile Function Questionnaire (IIEF) scores and objective, nocturnal penile tumescence and rigidity (NPT/ RigiScanÔ) measures were obtained and analyzed. RESULTS: Baseline clinical and demographic characteristics were not statistically different between the treatment groups. Seventy of the 94 patients (74.5%) completed the study. A total of 518 NPTR evaluations were performed using RigiScanÔ recorder. Pre-operatively,
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Vol. 191, No. 4S, Supplement, Monday, May 19, 2014
published clinical experience is limited. We report our experience with TTh in various categories of men with PCa. METHODS: A retrospective chart review identified 135 men (mean age 64 9y) with PCa who started TTh between May 2004 and Janurary 2013 and were followed for at least 6 months. Of these, 33 (24.4%) were on active surveillance (AS), 93 (68.9%) has undergone definitive local treatment for PCa and were without biochemical recurrence at the start of TTh, and 9 (6.7%) were treated with TTh after known biochemical recurrence. RESULTS: Of 33 men on AS, 3 men (9.1%) had upgrading on subsequent biopsy and 29 (87.9%) remained on AS over a mean follow-up of 31.2 mo. For 53 (39.3%) men starting TTh after radical prostatectomy, no patients had biochemical disease recurrence (PSA > 0.2ng/dL) over 30 mo of follow-up. Forty (29.6%) patients underwent either brachytherapy or XRT and were followed for an average of 26.7mo. Of these, 2(5%) patients developed PSA 2ng/dL over nadir but had subsequent PSAs below this threshold. Two (5%) men treated with radiotherapy elected for adjuvant HIFU. For the 9 (6.7%) patients with biochemically recurrent disease prior to starting T therapy, PSA continued to rise in 6 men without symptomatic metastatic disease over 28.7 months of follow-up. There were no skeletal-related events, and no deaths from prostate cancer in any group. Overall, 121 (89.6%) men with PCa remained on TTh with most men discontinuing therapy for lack of efficacy or other nononcologic reasons. CONCLUSIONS: TTh does not appear to cause higher than expected rates of PCa progression. A large majority of men with PCa treated with TTh will elect to continue treatment indefinitely. Source of Funding: none
MP48-09 TREATMENT OUTCOME OF CHEMICAL CASTRATION ON SEX OFFENDERS IN RELATION TO THE KINETICS OF SERUM TESTOSTERONE RECOVERY: IMPLICATIONS FOR DOSING SCHEDULE Kyo Chul Koo*, In Kyong Kim, Ho Chul Choi, Seung Hwan Lee, Sung Joon Hong, Byung Ha Chung, Seoul, Korea, Republic of INTRODUCTION AND OBJECTIVES: To evaluate outcomes of chemical castration on sexual offenders with a focus on the kinetics of serum testosterone (T) recovery. METHODS: This prospective analysis included 56 sex offenders imprisoned for sexual offenses. Thirty-eight and 18 patients who received 3 months and 6 months of leuprolide acetate injections were assigned to Group A and Group B, respectively. Psychobehavioral assessments and serum T levels were serially measured during the oncycle and the following observational 14-month off-cycle. RESULTS: Castrated levels of serum T reduced the frequency and intensity of sexual thoughts in 76% and 71% of Group A patients and in 78% and 72% of Group B patients, respectively. Reductions in masturbation frequency were observed in 74% of Group A and 83% of Group B patients. Wilson0 s Sex Fantasy Questionnaire (SFQ) scores also significantly reduced in both groups. In Group A, an upsurge of serum T to the flare-plateau level was observed during the first 2 months of the off-cycle, accompanied by an intense sexual drive and fantasy (Fig.1). In Group B, serum T gradually recovered to the baseline level and continued to upsurge beyond baseline levels during the observational period (Fig.2). SFQ scores of Group A returned to pre-treatment levels following the observational period; however, Wilson0 s SFQ scores of Group B remained suppressed. CONCLUSIONS: The efficacy of chemical castration varied according to the treatment duration. Regarding the kinetics of serum T recovery, maintaining at least 6 months of treatment warranted stable control of an excessive sexual drive following treatment cessation.
Source of Funding: none
MP48-10 TADALAFIL ONCE A DAY SIGNIFICANTLY REDUCES PENILE LENGTH-LOSS IN PATIENTS POST BILATERAL NERVE-SPARING RADICAL PROSTATECTOMY (NSRP) - RESULTS FROM A RANDOMIZED CONTROLLED TRIAL Gerald Brock*, London, Canada; Francesco Montorsi, Milan, Italy; Pierre Costa, Nîmes, France; Nimish Shah, Cambridge, United Kingdom; Jose Maria Martinez Jabaloyas, Valencia, Spain; Peter Hammerer, Braunschweig, Germany; Giuseppe M. Ludovico, Acquaviva delle Fonti, Bari, Italy; Carsten Henneges, Bad Homburg, Germany; Karim Hamidi, Neuilly Sur Seine, Germany; Andrea Rossi, €ttner, Bad Homburg, Germany; Sesto Fiorentino, Italy; Hartwig Bu John Mulhall, New York, NY INTRODUCTION AND OBJECTIVES: Secondary analyses on stretched penile length (SPL) data from a multicenter, randomized, double-blind, double-dummy, placebo (PLC) controlled clinical trial (NCT01026818) evaluating the efficacy of tadalafil (TAD) initiated postnsRP are reported. METHODS: Patients (pts) 68yrs with normal preoperative erectile function (EF) who underwent nsRP for localized prostate cancer (Gleason 7, PSA <10ng/mL) were randomized post nsRP 1:1:1 to 9month (mo) double-blind treatment (DBT) with TAD 5mg once a day (OaD), 20mg TAD on demand (pro re nata; PRN), or PLC, followed by 6-week drug-free washout (DFW)and 3mo open-label OaD treatment (OLT, all pts). Secondary outcome measures included change of SPL from baseline (nsRP) to end of 9mo DBT (eDBT)(LS mean change compared by prespecified ANCOVA, including terms for treatment, country, baseline, age, and Nerve Sparing Score [NSS]), responses to Sexual Encounter Profile Questions (SEP) 1 and 3 (mixed model for repeated measures including terms for treatment, country, visit, visittreatment interaction, age) and the Standardized Morning Erection Question (SMEQ; Cochrane Mantel Haenszel test adjusted for age and country).
THE JOURNAL OF UROLOGYâ
Vol. 191, No. 4S, Supplement, Monday, May 19, 2014
RESULTS: 423 pts were randomized to OaD (N¼139), PRN (N¼143), and PLC (N¼141); 114/122/155 completed 9mo DBT. Greater retained SPL was observed with OaD vs PLC at eDBT (Figure; LS mean [95%CI] difference OaD vs PLC, 4.1 [0.4, 7.8] mm, p¼0.032). No significant LS mean difference (p >0.05) was observed for PRN vs PLC. No significant effect of NSS on SPL loss was observed (Figure). Penile tumescense (SEP 1) as the initial sign of EF recovery was improved significantly vs. PLC at eDBT and OLT for pts randomized to OaD only. The ability for sexual intercourse (SEP 3) also significantly improved for pts on OaD vs placebo only at eDBT. The distribution of SMEQ responses was different at eDBT (p¼0.045), with 34.2% of pts on OaD, 50.0% on PRN and 56.5% on PLC reporting the absence of morning erections, At eDFW, SEP responses were not statistically significantly different between OaD and PLC. CONCLUSIONS: These data suggest that the early initiation of treatment with TAD OaD protects from penile length-loss and may contribute to protection from structural cavernosal changes post nsRP.
e531
significant improvements were observed in all endpoints, including successful intercourse attempts (SEP3) within approximately 15 minutes after dosing with both avanafil doses (P<.01 vs placebo; Table) and as early as 10 minutes post-dosing in the avanafil 200-mg group and 12 minutes post-dosing in the avanafil 100-mg group (P<.01 vs placebo). Common adverse events were headache, nasopharyngitis, and flushing. CONCLUSIONS: Avanafil had a significant erectogenic effect compared with placebo, including successful achievement of SEP2, SEP3, and changes in the IIEF-EF domain score. Furthermore, a significant number of sexual attempts were successful within approximately 15 minutes post-dosing. Table. Erectogenic Effects of Avanafil in Men With Mild to Severe ED During 8 Weeks of Treatment (ITT). Placebo
Avanfil 100 mg
Avanafil 200 mg
Successful Vaginal Penetration, SEP2 n LS Mean Percentage of Sexual Attempts (SE)
136
138
139
43.5 (3.2)
65.0 (3.2)*
65.4 (3.2)*
Successful Intercourse, SEP3 n LS Mean Percentage of Sexual Attempts (SE)
136
138
139
27.7 (3.3)
47.0 (3.3)*
48.7 (3.3)*
Successful Intercourse (SEP3) Within Approximately 15 Minutes Post-dosingz n LS Mean Percentage of Sexual Attempts (SE)
136
138
139
13.8 (2.9)
24.7 (2.9)y
28.2 (2.9)*
IIEF-EF Domain Score n LS Mean (SE)
Source of Funding: The study was funded by Eli Lilly and Company.
135
138
139
13.9 (0.8)
18.1 (0.8)*
19.1 (0.8)*
* P< .001 vs placebo; yP=.002 vs placebo; zAny erectogenic effect that had a stopwatch time of 17 minutes to include up to 17 minutes and 59 seconds could be considered to be within approximately 15 minutes. ITT, intent-to-treat population; LS, least squares; SE, standard error
Source of Funding: VIVUS, Inc.
MP48-11 TIME TO ERECTOGENIC EFFECT OF AVANAFIL IN A RANDOMIZED, PLACEBO-CONTROLLED TRIAL
MP48-12
Wayne J. G. Hellstrom*, New Orleans, LA; David Cook, Winston-Salem, NC; LeRoy Jones, San Antonio, TX; Charles H. Bowden, Wesley W. Day, Chien-Feng Chen, Mountain View, CA
EVALUATION OF NOCTURNAL TUMESCENCE AND ITS RESPONSE TO NIGHTLY SILDENAFIL CITRATE FOLLOWING RADICAL PROSTATECTOMY: A RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED STUDY
INTRODUCTION AND OBJECTIVES: Avanafil is a highly specific phosphodiesterase type 5 inhibitor approved for the treatment of erectile dysfunction (ED). This phase 4 study examined the efficacy and safety of avanafil approximately 15 minutes after dosing in men with mild to severe ED. METHODS: In this double-blind, 12-week (4-week run-in; 8-week treatment period) study, patients were randomized to placebo (n¼145), avanafil 100 mg (n¼147), or avanafil 200 mg (n¼148). Sexual function was assessed at baseline and at all follow-up visits using patient diaries and the International Index of Erectile Function (IIEF). The primary objective was to assess positive responses to Sexual Encounter Profile question 3 (SEP3) within approximately 15 minutes post-dosing. Patients were encouraged to attempt intercourse approximately 15 minutes post-dosing; stopwatches were used to measure timing of response. Other endpoints included the percentage of sexual attempts in which patients were able to insert the penis into the partner’s vagina (SEP2), percentage of successful sexual attempts in which patients maintained an erection of sufficient duration to have successful intercourse (SEP3), and change in the erectile function (EF) domain of IIEF. RESULTS: At baseline, mean age was 5810 years; 41% of patients had severe ED; mean duration of ED was 8970 months, and 60% had a history of sildenafil use. After 8 weeks of treatment,
Daniel Kim*, Dorota Hawksworth, Bethesda, MD; Judith Travis, Jennifer Cullen, Lauren Hurwitz, Rockville, MD; Stephen Brassell, Boise, ID; Inger Rosner, Bethesda, MD; Tom Lue, San Francisco, CA; Robert Dean, Bethesda, MD INTRODUCTION AND OBJECTIVES: Sildenafil citrate has been found efficacious therapy for post-prostatectomy impotence. In this study, we evaluated patterns of erectile function recovery following radical prostatectomy, and response to nightly therapy with Sildenafil citrate. METHODS: Ninety-four patients who underwent nerve sparing radical prostatectomy for localized prostate cancer were randomized to receive either a nightly 50mg dose of Sildenafil or placebo, starting on the first post-operative day and continuing for one year. Their erectile function was evaluated prior to surgery and at 2 weeks, 3, 6, 9, 12 and 13 months post-operatively. Both subjective, self-reported International Index of Erectile Function Questionnaire (IIEF) scores and objective, nocturnal penile tumescence and rigidity (NPT/ RigiScanÔ) measures were obtained and analyzed. RESULTS: Baseline clinical and demographic characteristics were not statistically different between the treatment groups. Seventy of the 94 patients (74.5%) completed the study. A total of 518 NPTR evaluations were performed using RigiScanÔ recorder. Pre-operatively,