Prostate Cancer, Male Erectile Disorder, Stage I Prostate Cancer, Stage II Prostate Cancer
Conditions
Brief summary
RATIONALE: Sildenafil citrate and alprostadil may help patients who have undergone prostatectomy for prostate cancer to recover from erectile dysfunction. PURPOSE: This randomized clinical trial is studying giving sildenafil together with alprostadil in treating patients undergoing nerve-sparing robotic-assisted radical prostatectomy for nonmetastatic prostate cancer.
Detailed description
PRIMARY OBJECTIVES: I. To determine the rate of erectile function (defined as the ability to achieve and maintain an erection sufficient for intercourse without the use of pharmacological assistance) at 1 year post-operatively in men undergoing BNS-RAP without the use of post-operative maintenance pharmacotherapy. II. To describe whether early post-operative maintenance pharmacotherapy Viagra can improve return of erectile function at 1 year post-operatively in patients undergoing BNS-RAP. III. To describe if early post-operative maintenance pharmacotherapy Viagra can decrease the time-to-return of erectile function in patients undergoing BNS-RAP. SECONDARY OBJECTIVES: I. To describe whether early post-operative maintenance pharmacotherapy MUSE can improve return of erectile function at 1 year post-operatively in patients undergoing BNS-RAP. II. To describe if early post-operative maintenance pharmacotherapy MUSE can decrease the time-to-return of erectile function in patients undergoing BNS-RAP. III. To compare sexual function quality of life in men undergoing early post-operative maintenance pharmacotherapy to those without early post-operative maintenance pharmacotherapy. IV. To compare the rate of potency at 1, 3, 6, 9, 12, and 18 months in men using Viagra versus MUSE for early post-operative maintenance pharmacotherapy. V. To describe the dropout rate for MUSE maintenance pharmacotherapy secondary to urethral pain in men using 2% Lidocaine lubricant. VI. To describe if penile length is decreased following BNS-RAP. VII. To describe if penile length at one year is different in men who have return of potency versus those with no return of potency. OUTLINE: Patients receive 2 doses of intraurethral alprostadil prior to undergoing bilateral nerve-sparing robotic-assisted prostatectomy. Within 4 weeks after surgery, patients are randomized to 1 of 3 treatment arms. ARM I: Patients receive intraurethral alprostadil once daily for up to 9 months in the absence of disease progression or unacceptable toxicity. Patients also receive 3 doses of oral sildenafil citrate at least 48 hours apart monthly for up to 18 months. ARM II: Patients receive 3 doses of oral sildenafil citrate on 3 separate occasions at least 48 hours apart monthly for 18 months. ARM III: Patients receive oral sildenafil citrate once daily for up to 9 months in the absence of disease progression or unacceptable toxicity. Patients also receive 3 doses of oral sildenafil citrate at least 48 hours apart monthly for up to 18 months. After completion of study treatment, patients are followed periodically for up to 18 months.
Interventions
DRUGsildenafil citrate
Given orally
DRUGalprostadil
Given intraurethrally
Undergo prostatectomy
PROCEDUREquality-of-life assessment
Ancillary studies
OTHERquestionnaire administration
Ancillary studies
Sponsors
City of Hope Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* All patients undergoing BNS-RAP for prostate cancer will be asked to participate * Ability to achieve erections sufficient for intercourse prior to surgery and an SHIMS-5 score of \>= 22 * Must maintain follow up care at COH for visits 1, 3, 6, 9, 12, and 18 months post surgery * Participants willing to participate on study for a minimum of 18 months * Consented participant on the Prostate database study (protocol 00149) * Patients must have a clinical stage of \< T3 * Gleason score \< 8 on post-operative pathological sample prior to randomization
Exclusion criteria
* Metastatic disease * Coronary artery disease on nitrate therapy (including oral sublingual nitrates) * Unable to maintain follow up visits at COH at 1, 3, 6, 9, 12, and 18 months post-operatively * Pathology diagnosis \>= pT3 * Prior hormonal treatment use for prostate cancer or low serum testosterone * Allergy to prostaglandin PGE1, Lidocaine, or Viagra * Gleason score \>= 8 on post-operative pathological sample prior to randomization * Concomitant use of cytochrome P450 3AY inhibitors (cimetidine, erythromycin, ketoconazole, or protease inhibitors) * SHIMS-5 score =\< 21
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Potency Rates (Ability to Obtain an Erection Sufficient for Penetration) Without Assistance Compared Between Patients in All Three Arms of the Study at 12 Months | 12 months following BNS-RAP | Potency rates (ability to obtain an erection sufficient for penetration) without assistance in those patients receiving maintenance Viagra compared to non-pharmacology controls was compared at 12 months from start of treatment using the fisher's exact test |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Potency Rates With or Without Assistance in the Control Group Versus Maintenance MUSE or Maintenance Viagra | At 6 and 18 months | Potency rates with or without assistance in the control group versus maintenance MUSE or maintenance Viagra were compared at each of 6 and 18 months |
| SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | At 1, 3, 6, 9, 12, and 18 months | Median and range of SHIM scores evaluated at 1, 3, 6, 9, 12, and 18 months. SHIMS-5 is the Sexual Health Inventory for Men, which includes 5 questions that are scored from 1 to 5 each. The total score is obtained by adding all five response scores, and can range from 5 to 25 when all 5 questions are answered. Questions that are left unanswered are scored as a 0, and can result in an overall score lower than 5 (as low as 0). Higher scores are more desirable. A Score of 22-25 = no ED, 17-21=Mild ED, 12-16=Mild to moderate ED, 8-11=Moderate ED, and 5-7 =Severe ED (ED=Erectile Dysfunction). There are no sub-scale scores within this questionnaire. |
| Penile Length | At pre-treatment and 18 months | measurement of penile length in centimeters |
Countries
United States
Participant flow
Recruitment details
10 patients were not randomized, for the following reasons: 1. ineligible upon surgery - 4 patients 2. patient withdrew or not returning to COH - 2 patients 3. did not have BNS procedure -- 2 patients (5) deemed to have sensitivity to MUSE -- 2 patients
Participants by arm
| Arm | Count |
|---|---|
| Sildenafil Citrate/Mo+Aprostadil/Day Patients receive intraurethral alprostadil once daily for up to 9 months in the absence of disease progression or unacceptable toxicity. Patients also receive 3 doses of oral sildenafil citrate at least 48 hours apart monthly for up to 18 months. Patients on all three arms will have undergone robotic-assisted laparoscopic surgery. All patients will take part in the questionnaire administration and quality-of-life assessments.
sildenafil citrate: Given orally
alprostadil: Given intraurethrally
robotic-assisted laparoscopic surgery: Undergo prostatectomy
quality-of-life assessment: Ancillary studies
questionnaire administration: Ancillary studies | 34 |
| Sildenafil Citrate Monthly Patients receive 3 doses of oral sildenafil citrate on 3 separate occasions at least 48 hours apart monthly for 18 months. Patients on all three arms will have undergone robotic-assisted laparoscopic surgery. All patients will take part in the questionnaire administration and quality-of-life assessments.
sildenafil citrate: Given orally
robotic-assisted laparoscopic surgery: Undergo prostatectomy
quality-of-life assessment: Ancillary studies
questionnaire administration: Ancillary studies | 35 |
| Sildenafil Citrate Monthly Daily Sildenafil Citrate Patients receive oral sildenafil citrate once daily for up to 9 months in the absence of disease progression or unacceptable toxicity. Patients also receive 3 doses of oral sildenafil citrate at least 48 hours apart monthly for up to 18 months. Patients on all three arms will have undergone robotic-assisted laparoscopic surgery. All patients will take part in the questionnaire administration and quality-of-life assessments.
sildenafil citrate: Given orally
robotic-assisted laparoscopic surgery: Undergo prostatectomy
quality-of-life assessment: Ancillary studies
questionnaire administration: Ancillary studies | 31 |
| Total | 100 |
Baseline characteristics
| Characteristic | Sildenafil Citrate/Mo+Aprostadil/Day | Total | Sildenafil Citrate Monthly Daily Sildenafil Citrate | Sildenafil Citrate Monthly |
|---|---|---|---|---|
| Age, Continuous | 58 years | 58 years | 59 years | 58 years |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 31 Participants | 88 Participants | 25 Participants | 32 Participants |
| Region of Enrollment United States | 34 Participants | 100 Participants | 31 Participants | 35 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 34 Participants | 100 Participants | 31 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 35 | 0 / 31 |
| other Total, other adverse events | 24 / 34 | 19 / 35 | 24 / 31 |
| serious Total, serious adverse events | 0 / 34 | 0 / 35 | 0 / 31 |
Outcome results
Primary
Potency Rates (Ability to Obtain an Erection Sufficient for Penetration) Without Assistance Compared Between Patients in All Three Arms of the Study at 12 Months
Potency rates (ability to obtain an erection sufficient for penetration) without assistance in those patients receiving maintenance Viagra compared to non-pharmacology controls was compared at 12 months from start of treatment using the fisher's exact test
Time frame: 12 months following BNS-RAP
Population: These are the patients who remained on treatment for the duration of the 12 months and were evaluable at that time point.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sildenafil Citrate/Mo+Aprostadil/Day | Potency Rates (Ability to Obtain an Erection Sufficient for Penetration) Without Assistance Compared Between Patients in All Three Arms of the Study at 12 Months | 13 Participants |
| Sildenafil Citrate Monthly | Potency Rates (Ability to Obtain an Erection Sufficient for Penetration) Without Assistance Compared Between Patients in All Three Arms of the Study at 12 Months | 16 Participants |
| Daily Sildenafil Citrate | Potency Rates (Ability to Obtain an Erection Sufficient for Penetration) Without Assistance Compared Between Patients in All Three Arms of the Study at 12 Months | 16 Participants |
p-value: >0.1Fisher Exact
Secondary
Penile Length
measurement of penile length in centimeters
Time frame: At pre-treatment and 18 months
Population: patients who were willing to have penile measurements taken at baseline
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sildenafil Citrate/Mo+Aprostadil/Day | Penile Length | Baseline Penile Measurement | 11 centimeters |
| Sildenafil Citrate/Mo+Aprostadil/Day | Penile Length | Month 18 Penile Measurement | 12.5 centimeters |
| Sildenafil Citrate Monthly | Penile Length | Baseline Penile Measurement | 12 centimeters |
| Sildenafil Citrate Monthly | Penile Length | Month 18 Penile Measurement | 11 centimeters |
| Daily Sildenafil Citrate | Penile Length | Baseline Penile Measurement | 10.2 centimeters |
| Daily Sildenafil Citrate | Penile Length | Month 18 Penile Measurement | 12 centimeters |
Comparison: ANOVA test to compare difference of penile length (from baseline to month 18) across arms.~calculations are underpowered, as study did not accrue or retain patients as intended, and many patients declined to have measurements taken.p-value: 0.08ANOVA
Secondary
Potency Rates With or Without Assistance in the Control Group Versus Maintenance MUSE or Maintenance Viagra
Potency rates with or without assistance in the control group versus maintenance MUSE or maintenance Viagra were compared at each of 6 and 18 months
Time frame: At 6 and 18 months
Population: patients who were evaluated at 6 months, 18 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sildenafil Citrate/Mo+Aprostadil/Day | Potency Rates With or Without Assistance in the Control Group Versus Maintenance MUSE or Maintenance Viagra | 18 month potency | 14 Participants |
| Sildenafil Citrate/Mo+Aprostadil/Day | Potency Rates With or Without Assistance in the Control Group Versus Maintenance MUSE or Maintenance Viagra | 6 month potency | 10 Participants |
| Sildenafil Citrate Monthly | Potency Rates With or Without Assistance in the Control Group Versus Maintenance MUSE or Maintenance Viagra | 6 month potency | 11 Participants |
| Sildenafil Citrate Monthly | Potency Rates With or Without Assistance in the Control Group Versus Maintenance MUSE or Maintenance Viagra | 18 month potency | 16 Participants |
| Daily Sildenafil Citrate | Potency Rates With or Without Assistance in the Control Group Versus Maintenance MUSE or Maintenance Viagra | 6 month potency | 17 Participants |
| Daily Sildenafil Citrate | Potency Rates With or Without Assistance in the Control Group Versus Maintenance MUSE or Maintenance Viagra | 18 month potency | 15 Participants |
Comparison: compare percentage of patients potent at 6 and 18 months across pairs of treatment arms (arm I vs arm II, arm I vs arm III, arm II vs arm III)p-value: >0.1Chi-squared
Secondary
SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups
Median and range of SHIM scores evaluated at 1, 3, 6, 9, 12, and 18 months. SHIMS-5 is the Sexual Health Inventory for Men, which includes 5 questions that are scored from 1 to 5 each. The total score is obtained by adding all five response scores, and can range from 5 to 25 when all 5 questions are answered. Questions that are left unanswered are scored as a 0, and can result in an overall score lower than 5 (as low as 0). Higher scores are more desirable. A Score of 22-25 = no ED, 17-21=Mild ED, 12-16=Mild to moderate ED, 8-11=Moderate ED, and 5-7 =Severe ED (ED=Erectile Dysfunction). There are no sub-scale scores within this questionnaire.
Time frame: At 1, 3, 6, 9, 12, and 18 months
Population: patients with shim scores at 1 month
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sildenafil Citrate/Mo+Aprostadil/Day | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 1 month | 9.5 units on a scale |
| Sildenafil Citrate/Mo+Aprostadil/Day | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 3 months | 14 units on a scale |
| Sildenafil Citrate/Mo+Aprostadil/Day | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 6 months | 18 units on a scale |
| Sildenafil Citrate/Mo+Aprostadil/Day | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 9 months | 18.5 units on a scale |
| Sildenafil Citrate/Mo+Aprostadil/Day | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 12 months | 20 units on a scale |
| Sildenafil Citrate/Mo+Aprostadil/Day | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 18 months | 19.5 units on a scale |
| Sildenafil Citrate Monthly | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 18 months | 20 units on a scale |
| Sildenafil Citrate Monthly | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 1 month | 3 units on a scale |
| Sildenafil Citrate Monthly | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 9 months | 17.5 units on a scale |
| Sildenafil Citrate Monthly | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 12 months | 19 units on a scale |
| Sildenafil Citrate Monthly | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 3 months | 14 units on a scale |
| Sildenafil Citrate Monthly | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 6 months | 18.5 units on a scale |
| Daily Sildenafil Citrate | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 3 months | 18 units on a scale |
| Daily Sildenafil Citrate | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 6 months | 20 units on a scale |
| Daily Sildenafil Citrate | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 18 months | 20.5 units on a scale |
| Daily Sildenafil Citrate | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 9 months | 19 units on a scale |
| Daily Sildenafil Citrate | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 1 month | 12 units on a scale |
| Daily Sildenafil Citrate | SHIMS-5 Scores in the Control Groups Versus Maintenance MUSE or Maintenance Viagra Groups | SHIM score 12 months | 18 units on a scale |
p-value: >0.2ANOVA