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Biomedical subjects

G L Andriole

Publications and source records attributed to G L Andriole.

At least 19 recordsLinked to original sources
PubMed2004

Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia.

OBJECTIVES: To examine the rate of prostate cancer detection in three large randomized placebo-controlled benign prostatic hyperplasia trials of dutasteride. Dutasteride, which lowers serum dihydrotestosterone more than 93% by inhibiting type 1 and type 2 5-alpha-reductase, is effective in the treatment of benign prostatic hyperplasia. However, its effect on the development of prostate cancer is unknown. METHODS: A total of 4325 men with benign prostatic hyperplasia but without a history, or evidence, of prostate cancer, and a serum prostate-specific antigen level of 1.5 to 10 ng/mL, were randomized to 0.5 mg/day dutasteride or placebo for 24 months. The prostate cancer detection rates for subjects were determined by non-protocol-mandated biopsies, either during the double-blind phase of the study or during the first 3 months of the open-label extension. A follow-up questionnaire was administered to a subset of consenting subjects to ascertain the number, outcomes, and reasons for the prostate biopsies. RESULTS: The cumulative incidence of prostate cancer as an adverse event was significantly lower in the dutasteride versus placebo group at 24 months (1.1% versus 1.9%, P = 0.025) and 27 months (1.2% versus 2.5%, P = 0.002). There were no differences in the diagnosis rates of prostate cancer during the first 15 months, after which time the detection rate of prostate cancer increased in the placebo group and remained low in the dutasteride group. CONCLUSIONS: Prostate cancer detection was significantly lower in subjects randomized to dutasteride compared with the placebo group. These results have prompted the initiation of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study, which was designed and powered to test the hypothesis that treatment with dutasteride decreases the incidence and progression of prostate cancer.

5-alpha Reductase Inhibitors↗
PubMed2004

Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer.

PURPOSE: In the prostate testosterone is converted to dihydrotestosterone (DHT) by the enzymes 5alpha-reductase (5alphaR) types 1 and 2 (5alphaR1 and 5alphaR2). Suppression of DHT formation by 5alphaR inhibition may be beneficial in early treatment or prevention of prostate cancer. Although 5alphaR2 is the dominant enzyme in the prostate, evidence indicates that 5alphaR1 may be up-regulated in some prostate cancers. This suggests that dual inhibition of both isoenzymes may be more effective than suppression of 5alphaR2 alone in prostate cancer treatment or prevention. In this short-term pilot study we examined the effect of the dual 5alphaR inhibitor dutasteride on markers of tumor regression. MATERIALS AND METHODS: A total of 46 men with clinically staged T1 or T2 prostate cancer were randomized to receive 5 mg per day of placebo or dutasteride for 6 to 10 weeks before radical prostatectomy. Resected tissues were analyzed to determine the effect of dutasteride on intraprostatic androgen levels, and indices of apoptosis and microvessel density (MVD) in malignant tissue, as well as degree of atrophy in benign tissue. RESULTS: Treatment with dutasteride caused a 97% decrease in intraprostatic DHT and was associated with a trend toward increased apoptosis. In patients receiving dutasteride for 45 days or more, a significant increase in apoptosis and a trend toward decreased MVD in prostate cancer tissue was observed. Dutasteride treatment was also associated with an 18% decrease in mean benign epithelial cell width compared with placebo (p < 0.0001). CONCLUSIONS: In this pilot study dutasteride treatment resulted in almost complete suppression of intraprostatic DHT, increased apoptosis and a trend toward decreased MVD. These findings suggest that short-term treatment with dutasteride can cause regression in some prostate cancers.

5-alpha Reductase Inhibitors↗
PubMed2004

Risk behaviours and benign prostatic hyperplasia.

OBJECTIVE: To identify risk factors for benign prostatic hyperplasia (BPH). SUBJECTS AND METHODS: Medical history data, including reported urological conditions and treatments, and risk factor data were collected from 34 694 participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial designed to evaluate methods for the early detection of cancer. RESULTS: Asian men had the lowest risks (odds ratio, 95% confidence interval) for nocturia (0.7, 0.5-0.9), physician-diagnosed BPH (0.3, 0.2-0.5) and transurethral prostatectomy (TURP, 0.2, 0.1-0.6), while risks for Whites and Blacks were similar for most measures of BPH. Greater alcohol intake was associated with decreased nocturia (P trend = 0.002), BPH (P trend < 0.001) and TURP (P trend < 0.001). Current tobacco use was associated with decreased nocturia (0.8, 0.7-0.9), BPH (0.7, 0.6-0.8) and TURP (0.6, 0.4-0.8) but dose-response patterns were weak. CONCLUSION: Asian-Americans have the lowest risk of clinical BPH. Alcohol and possibly cigarettes are related to a lower risk for BPH.

Age Distribution↗
PubMed2001

Relationship of demographic and clinical factors to free and total prostate-specific antigen.

OBJECTIVES: To characterize the role of demographic and clinical parameters in the measurements of prostate-specific antigen (PSA), free PSA (fPSA), and percent free PSA (%fPSA). METHODS: This was a cohort study of volunteers to a randomized screening trial. A central laboratory determined PSA and fPSA for the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. A baseline evaluation of free and total PSA was done for 7183 white, black, Asian, Hispanic, and other male volunteers, aged 55 to 74 years. Comparisons were made across racial and ethnic groups and across a set of clinical parameters from a baseline questionnaire. RESULTS: The median levels of serum PSA were less than 2.1 ng/mL in each age-race grouping of the study participants. The levels of free and total PSA were higher in black (n = 868, 12%) participants than in white (n = 4995, 70%) and Asian (n = 849, 11.8%) participants. Individuals who identified themselves as ethnically Hispanic (n = 339, 4.7%) had median PSA levels higher than whites who were not Hispanic. The free and total PSA levels increased with age, particularly among men 70 to 74 years old. However, the %fPSA levels showed less variation among the four racial groups or by age. The free and total PSA levels were higher among those who had a history of benign prostatic disease. CONCLUSIONS: Demographic (age and race/ethnicity) and clinical (history of benign prostatic disease) variables had a moderate effect on the measures of PSA and fPSA and very little effect on %fPSA.

Aged↗
PubMed2001

Preoperative oral rofecoxib does not decrease postoperative pain or morphine consumption in patients after radical prostatectomy: a prospective, randomized, double-blinded, placebo-controlled trial.

STUDY OBJECTIVES: To evaluate the analgesic efficacy of the rofecoxib po before radical prostatectomy. DESIGN: Prospective, randomized, double-blinded, placebo-controlled trial. SETTING: Teaching hospital. PATIENTS: Anesthetic management was standardized. Patients received either a 50-mg rofecoxib capsule or a placebo capsule po 1 hour before induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Patient-generated 10-cm visual analog scale (VAS) scores for pain were assessed at 1, 2, 4, 6, 8, and 24 hours after surgery. Morphine consumption was recorded from a patient-controlled analgesia device at the same time. A patient-generated overall pain relief score was obtained at 24 hours after surgery. We were unable to detect any differences between study groups with respect to postoperative morphine consumption, VAS score, or overall pain relief score. CONCLUSIONS: When rofecoxib is used po in maximum recommended doses before surgery, it does not provide significant analgesia that results in reduction in pain scores or analgesic requirements for patients after radical prostatectomy.

Aged↗
PubMed2000

The natural history, skeletal complications, and management of bone metastases in patients with prostate carcinoma.

BACKGROUND: Prostate carcinoma poses a significant public health problem. Although a minority of men with newly diagnosed prostate carcinoma manifest bone metastases or skeletal abnormalities, a significant proportion of men will develop these complications over the course of their lives. Patients at highest risk for bone metastases include those with high grade, high stage neoplasms, those who fail primary curative therapies such as radical prostatectomy or radiation therapy, and those who develop biochemical recurrence after hormonal therapy. METHODS: The relative risks and prognostic factors for bone metastases in each of these settings will be reviewed. RESULTS: In comparison with men without prostate carcinoma, benign skeletal complications (osteopenia and fractures) occur at significantly increased rates among men with untreated prostate carcinoma. Moreover, the incidence rate of these conditions increases dramatically among those men who are receiving endocrine therapy. The duration and intensity of the endocrine therapy may be associated with the incidence rate and severity of skeletal complications. CONCLUSIONS: Given the significant incidence rate and quality of life implications of skeletal complications and bone metastases, there is an urgent need to identify effective preventive therapies and treatments. Bisphosphonates may have a role in preventing osteopenia and, potentially, bone metastases among men with prostate carcinoma.

Bone Neoplasms↗
PubMed2000

Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

The objectives of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55-74 at entry whether screening with flexible sigmoidoscopy (60-cm sigmoidoscope) can reduce mortality from colorectal cancer, whether screening with chest X-ray can reduce mortality from lung cancer, whether screening men with digital rectal examination (DRE) plus serum prostate-specific antigen (PSA) can reduce mortality from prostate cancer, and whether screening women with CA125 and transvaginal ultrasound (TVU) can reduce mortality from ovarian cancer. Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity, specificity, and positive predictive value; to assess incidence, stage, and survival of cancer cases; and to investigate biologic and/or prognostic characterizations of tumor tissue and biochemical products as intermediate endpoints. The design is a multicenter, two-armed, randomized trial with 37,000 females and 37,000 males in each of the two arms. In the intervention arm, the PSA and CA125 tests are performed at entry, then annually for 5 years. The DRE, TVU, and chest X-ray exams are performed at entry and then annually for 3 years. Sigmoidoscopy is performed at entry and then at the 5-year point. Participants in the control arm follow their usual medical care practices. Participants will be followed for at least 13 years from randomization to ascertain all cancers of the prostate, lung, colorectum, and ovary, as well as deaths from all causes. A pilot phase was undertaken to assess the randomization, screening, and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels. This paper describes eligibility, consent, and other design features of the trial, randomization and screening procedures, and an outline of the follow-up procedures. Sample-size calculations are reported, and a data analysis plan is presented.

Colorectal Neoplasms↗
PubMed2000

Safety and efficacy of an implantable leuprolide delivery system in patients with advanced prostate cancer.

PURPOSE: We evaluated the pharmacokinetics, safety and efficacy of the implantable Viadur++ leuprolide delivery system during 12 months in patients with advanced prostate cancer. MATERIALS AND METHODS: Our open label, multicenter, dose ranging study was done in 2 phases. The treatment phase was a stratified, randomized, parallel evaluation of the safety and efficacy of 1 or 2 implants. The safety extension phase assessed the long-term safety and efficacy of 1 implant. Implant insertion and removal, pharmacokinetic profile and patient satisfaction were also evaluated. The primary efficacy parameter was testosterone suppression for 12 months but luteinizing hormone and prostate specific antigen were also evaluated. RESULTS: Of the 51 patients 27 received 1 and 24 received 2 implants, of whom 49 completed the 12-month treatment phase. Steady serum leuprolide concentration was maintained from day 3 through the remainder of the 12-month treatment phase and for 2 months after reimplantation. Implantation and reimplantation were well tolerated and acceptable to physicians and patients. Testosterone suppression to the castrate range was 100% in each group. At 12 months mean prostate specific antigen decreased from a baseline of approximately 84% and 91% in groups 1 and 2, respectively. Serious adverse events during the study period in 15 patients were not attributable to treatment. CONCLUSIONS: The implantable leuprolide delivery system provides effective suppression of testosterone in patients with advanced prostate cancer.

Aged↗
PubMed1999

Anaemia in men receiving combined finasteride and flutamide therapy for advanced prostate cancer.

OBJECTIVE: To determine the effect of combined finasteride and flutamide therapy on haemoglobin and haematocrit values in men with advanced prostate cancer. PATIENTS AND METHODS: Nineteen men, previously untreated by hormone therapy, with histologically confirmed adenocarcinoma of the prostate and clinical evidence of advanced disease, were treated with combined finasteride (5 mg/day) and flutamide (750 mg/day) for at least 6 months. Complete blood counts were performed before initiation and after 6 months of therapy. RESULTS: After 6 months of finasteride and flutamide therapy both haemoglobin levels and haematocrit decreased in all men, with a mean (sd, range) decrease of 16 (10, 3-42) g/L and 4.6 (2.7, 0.8-9.9)%, respectively. CONCLUSION: Combined finasteride and flutamide therapy significantly lowers haemoglobin and haematocrit levels in men with advanced prostate cancer, and further study of this effect is warranted.

Aged↗
PubMed1999

A prospective randomized comparison of three blood conservation strategies for radical prostatectomy.

BACKGROUND: Preoperative autologous blood donation is a standard of care for elective surgical procedures requiring transfusion. The authors evaluated the efficacy of alternative blood-conservation strategies including preoperative recombinant human erythropoietin (rHuEPO) therapy and acute normovolemic hemodilution (ANH) in radical retropubic prostatectomy patients. METHODS: Seventy-nine patients were prospectively randomized to preoperative autologous donation (3 U autologous blood); rHuEPO plus ANH (preoperative subcutaneous administration of 600 U/kg rHuEPO at 21 and 14 days before surgery and 300 U/kg on day of surgery followed by ANH in the operating room); or ANH (blinded, placebo injections per the rHuEPO regimen listed previously). Transfusion outcomes, perioperative hematocrit levels, postoperative outcomes, and blood-conservation costs were compared among the three groups. RESULTS: Baseline hematocrit levels were similar in all groups (43%+/-2%). On the day of surgery hematocrit decreased to 34% +/-4% in the preoperative autologous donation group (P < 0.001), increased to 47%+/-2% in the rHuEPO plus ANH group (P < 0.001), and remained unchanged at 43%+/-2% in the ANH group. Allogeneic blood exposure was similar in all groups. The rHuEPO plus ANH group had significantly higher hematocrit levels compared with the other groups throughout the hospitalization (P < 0.001). Average transfusion costs were significantly lower for ANH ($194+/-$192) compared with preoperative autologous donation ($690+/-$128; P < 0.001) or rHuEPO plus ANH ($1,393+/-$204, P < 0.001). CONCLUSIONS: All three blood-conservation strategies resulted in similar allogeneic blood exposure rates, but ANH was the least costly technique. Preoperative rHuEPO plus ANH prevented postoperative anemia but resulted in the highest transfusion costs.

Aged↗
PubMed1999

Hormonal manipulation for rising PSA after radical prostatectomy.

PSA recurrence after radical prostatectomy usually indicates recurrent prostate cancer. Identification of the recurrence site is difficult, but pathological and clinical features may suggest local versus distant recurrence. Radiographic techniques including transrectal ultrasonography, and 111indium capromab pendetide scans may help identify recurrences. The use of hormonal manipulation for rising PSA after radical prostatectomy is controversial. Androgen deprivation has been a mainstay of the management for advanced prostate cancer. The timing of such therapy is debatable, and early therapy in an asymptomatic patient may not correlate with improved survival. Maximal androgenic blockade with castration and nonsteroidal antiandrogens may offer a modest survival benefit in selected patients. Novel potency-sparing therapies with antiandrogens and finasteride afford an improved patient lifestyle, with questionable effects on survival. Intermittent androgen suppression is an experimental treatment modality that may reduce the side effects of castration. Ongoing studies are being performed to clarify these controversies, and the variety of treatment options allows patients great flexibility in considering quality of life and effective cancer control.

Androgen Antagonists↗
PubMed1998

Treatment with finasteride preserves usefulness of prostate-specific antigen in the detection of prostate cancer: results of a randomized, double-blind, placebo-controlled clinical trial. PLESS Study Group. Proscar Long-term Efficacy and Safety Study.

OBJECTIVES: To evaluate prostate cancer detection and prostate-specific antigen (PSA) among men with benign prostatic hyperplasia treated with finasteride. METHODS: Three thousand forty men 45 to 78 years of age with PSA less than 10 ng/mL and no history of prostate cancer were randomized in a double-blind, placebo-controlled trial to finasteride (n = 1524) or placebo (n = 1516) for up to 4 years. A prerandomization biopsy negative for prostate cancer was obtained in 98% of patients with a screening PSA of 4.0 ng/mL or more, and an end-of-study biopsy was requested of all such patients without a recent second negative biopsy or a prostate cancer diagnosis. RESULTS: Overall, 644 patients (21%) underwent biopsy and 201 (6.6%) underwent transurethral resection of the prostate. Prostate cancer was diagnosed in 4.7% of men on finasteride and 5.1% on placebo (P = 0.7). Elevated PSA prompted diagnosis in 35% of cases on finasteride and 34% on placebo. The area under the receiver operating characteristic curve for last PSA was 0.84 on finasteride and 0.79 on placebo (P = 0.07). Use of an upper limit of normal for last PSA of 2.0 ng/mL for finasteride and 4.0 ng/mL for placebo yielded similar sensitivity (66% versus 70%, P = 0.6), higher specificity (82% versus 74%, P < 0.0001), and a higher likelihood ratio (3.6 versus 2.7, P < 0.05) for finasteride than for placebo. CONCLUSIONS: In men treated with finasteride, multiplying PSA by 2 and using normal ranges for untreated men preserves the usefulness of PSA for prostate cancer detection.

Aged↗
PubMed1998

Biochemical response to testicular androgen ablation among patients with prostate cancer for whom flutamide and/or finasteride therapy failed.

OBJECTIVES: To evaluate the response of testicular androgen ablation in patients with advanced prostate cancer with a biochemical recurrence after finasteride or combined finasteride and flutamide therapy. METHODS: Eighteen hormone naïve men with advanced prostate cancer (10 with detectable prostate-specific antigen [PSA] levels after radical prostatectomy, 4 with rising PSA levels after definitive radiation therapy, and 4 with Stage D2 disease) were treated with finasteride (5 mg/day) alone or in combination with flutamide (250 mg three times a day). All men experienced an initial reduction in serum PSA, but later had treatment failure with two consecutive rising PSA measurements. All men were then treated with testicular androgen ablation (bilateral orchiectomy in 15 and luteinizing hormone-releasing hormone analogue in 3). RESULTS: Overall, serum PSA declined by more than 80% in 15 (83%) of 18 and to undetectable levels in 14 (78%) of 18. With a median+/-semi-interquartile range follow-up of 22+/-14.5 months from the initiation of hormone therapy, 12 (67%) of 18 currently have undetectable PSA levels. Two men having rising serum PSA levels above 100 ng/mL and 1 man has died from complications of metastatic prostate cancer. CONCLUSIONS: Testicular androgen ablation effectively lowers serum PSA levels in most men with advanced prostate cancer who have experienced a biochemical recurrence despite initial response and subsequent relapse on finasteride or combined finasteride and flutamide therapy.

Aged↗
PubMed1998

Evaluation and management of the man who has failed primary curative therapy for prostate cancer.

The recurrence of prostate cancer after potentially curative local therapy is becoming a significant urologic problem. There are few prospective randomized trials, and the optimal diagnostic and treatment strategies for men who fail potentially curative therapy are not known. The experience to date seems to suggest the following as a reasonable approach. A detectable serum PSA level (> or = 0.4 ng/mL) after radical prostatectomy is evidence of residual or recurrent prostate cancer. Men with low- or moderate-grade cancers (Gleason score < 7), with capsular penetration, or with positive surgical margins in whom disease recurs more than 2 years after radical prostatectomy with a PSA doubling time greater than 12 months seem likely to harbor a local recurrence and are the only good candidates for salvage therapy. Unless there is a palpable recurrence, transrectal ultrasound and biopsy are generally not recommended, and CT scanning and bone scintigraphy usually do not provide helpful information. The role of monoclonal antibody scanning is currently investigational. Men with high-grade tumors (Gleason score > or = 7) or with seminal vesicle or lymph node involvement in whom disease recurs within 2 years of radical prostatectomy are most appropriately observed or treated with early hormonal therapy. Men who do not achieve a PSA nadir of 0.5 ng/mL or less within 2 years of radiotherapy are very likely to harbor residual disease. For young healthy men who are willing to accept a substantial risk of impotency, urinary incontinence, and bladder neck contractures, salvage radical prostatectomy is a reasonable option if the preradiation tumor characteristics are acceptable (PSA < 10 ng/mL, Gleason score < or = 6) and if the current PSA is less than 10 ng/mL. Salvage cryotherapy may result in substantial morbidity and should only be offered on an investigational basis. Other men failing radiation may be observed or treated with hormonal therapy. There is seldom a role for repeat biopsy. Because the optimal time to begin hormone therapy is still not known, early or delayed treatment are both reasonable options. Testicular androgen ablation by orchiectomy or LHRH agonists is considered standard therapy. Combined therapy with an antiandrogen does not seem to be beneficial for all patients and should not be routinely used. Sexually active men in whom preservation of potency is important can be offered an investigational regimen such as a 5-alpha-reductase inhibitor combined with an oral antiandrogen or intermittent LHRH agonist therapy. It is hoped that the results of ongoing randomized trials and future research will establish efficient and effective practice guidelines to evaluate and treat men who have failed potentially curative therapy for localized prostate cancer. This remains a very important and controversial topic that will challenge many practicing urologists.

Cryotherapy↗
PubMed1997

Comparison of percent free prostate-specific antigen levels in men with benign prostatic hyperplasia treated with finasteride, terazosin, or watchful waiting.

OBJECTIVES: Finasteride is known to lower total serum prostate-specific antigen (PSA) levels by approximately 50%. Terazosin is thought to have little or no effect on serum PSA concentration. The objective of our study was to determine the effect of finasteride and terazosin on serum total and serum free PSA levels and the ratio of free to total PSA. METHODS: We identified 69 men with symptomatic benign prostatic hyperplasia (BPH) who had been receiving 5 mg/day (n = 33) of finasteride or 2 to 5 mg/day (n = 14) of terazosin or no therapy ("watchful waiting") (n = 22). The three groups were compared with respect to pretreatment total serum PSA levels and post-treatment total, free, and percent free serum PSA levels. RESULTS: Median (+/- semi-interquartile range [SIR]) pretreatment total serum PSA levels (ng/mL) were not significantly different in men taking finasteride (2.8 +/- 1.9), terazosin (2.2 +/- 2.5), or undergoing watchful waiting (5.5 +/- 1.4) (P = 0.12). The median (+/- SIR) post-treatment total serum PSA levels (ng/mL) were significantly lower in the finasteride group (1.1 +/- 1) when compared with the terazosin (2.5 +/- 1.5) or watchful waiting (4.3 +/- 2.8) groups (P = 0.016). Only the finasteride group had significantly lower post-treatment total serum PSA levels compared with pretreatment levels. The median (+/- SIR) post-treatment free PSA levels were significantly lower in the finasteride group (0.26 +/- 0.16) compared with the terazosin (0.54 +/- 0.5) and watchful waiting (0.85 +/- 0.5) groups (P = 0.0015). However, the median (+/- SIR) percent free PSA was not significantly different in the finasteride (23 +/- 6), terazosin (22 +/- 4), and watchful waiting (25 +/- 5) groups (P = 0.66). CONCLUSIONS: Finasteride appears to lower total and free PSA levels equally in men with BPH and does not appear to change the ratio of free to total serum PSA. Terazosin does not appear to alter total or free serum PSA levels in men with BPH. The percent free PSA could potentially be used to screen for prostate cancer in men taking finasteride. Prospective studies are needed to further evaluate this issue.

Adrenergic alpha-Antagonists↗