Biomedical subjects

T Wilt

Publications and source records attributed to T Wilt.

12 recordsLinked to original sources

PubMed2002

Pygeum africanum for benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH), nonmalignant enlargement of the prostate, can lead to obstructive and irritative lower urinary tract symptoms (LUTS). The pharmacologic use of plants and herbs (phytotherapy) for the treatment of LUTS associated with BPH has been growing steadily. The extract of the African prune tree, Pygeum africanum, is one of the several phytotherapeutic agents available for the treatment of BPH. OBJECTIVES: To investigate the evidence whether extracts of Pygeum africanum (1) are more effective than placebo in the treatment of Benign Prostatic Hyperplasia (BPH), (2) are as effective as standard pharmacologic BPH treatments, and (3) have less side effects compared to standard BPH drugs. SEARCH STRATEGY: Trials were searched in computerized general and specialized databases (MEDLINE (1966-2000), EMBASE, Cochrane Library, Phytodok), by checking bibliographies, and by contacting relevant manufacturers and researchers. SELECTION CRITERIA: Trials were eligible if they (1) were randomized (2) included men with BPH (3) compared preparations of Pygeum africanum (alone or in combination) with placebo or other BPH medications (4) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements. Eligibility was assessed by at least two independent observers. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, and outcomes were extracted by at least two independent reviewers using a standard form. The main outcome measure for comparing the effectiveness of Pygeum africanum with placebo and standard BPH medications was the change in urologic symptoms scale scores. Secondary outcomes included change in urologic symptoms including nocturia and urodynamic measures (peak and mean urine flow, prostate size). The main outcome measure for adverse effects was the number of men reporting adverse effects. MAIN RESULTS: A total of 18 randomized controlled trials involving 1562 men met inclusion criteria and were analyzed. Only one of the studies reported a method of treatment allocation concealment, though 17 were double-blinded. There were no studies comparing Pygeum africanum to standard pharmacologic interventions such as alpha-adrenergic blockers or 5-alpha reductase inhibitors. The mean study duration was 64 days (range, 30-122 days). Many studies did not report results in a method that permitted meta-analysis. Compared to men receiving placebo, Pygeum africanum provided a moderately large improvement in the combined outcome of urologic symptoms and flow measures as assessed by an effect size defined by the difference of the mean change for each outcome divided by the pooled standard deviation for each outcome (-0.8 SD [95% confidence interval (CI), -1.4, -0.3 (n=6 studies)]). Men using Pygeum africanum were more than twice as likely to report an improvement in overall symptoms (RR=2.1, 95% CI = 1.4, 3.1). Nocturia was reduced by 19%, residual urine volume by 24% and peak urine flow was increased by 23%. Adverse effects due to Pygeum Africanum were mild and comparable to placebo. The overall dropout rate was 12% and was similar between Pygeum Africanum (13%), placebo (11%) and other controls (8%). REVIEWER'S CONCLUSIONS: A standardized preparation of Pygeum africanum may be a useful treatment option for men with lower urinary symptoms consistent with benign prostatic hyperplasia. However, the reviewed studies were small in size, were of short duration, used varied doses and preparations and rarely reported outcomes using standardized validated measures of efficacy. Additional placebo-controlled trials are needed as well as studies that compare Pygeum africanum to active controls that have been convincingly demonstrated to have beneficial effects on lower urinary tract symptoms related to BPH. These trials should be of sufficient size and duration to detect important differences in clinically relevant endpoints and use standardized urologic symptom scale scores.

Humans↗

PubMed2002

Early versus deferred androgen suppression in the treatment of advanced prostatic cancer.

BACKGROUND: Prostate cancer is a leading cause of cancer death in men. Treatment goals for men with advanced prostate cancer include prolonging survival, preventing or delaying symptoms due to disease progression, improving and maintaining quality of life, reducing treatment related morbidity. Androgen suppression therapy is considered a mainstay of treatment for men with advanced prostate cancer. However it is not clear whether early androgen suppression for men with locally advanced disease or asymptomatic metastases improves length and quality of life compared to androgen suppression deferred until signs and symptoms of clinical progression. OBJECTIVES: This systematic review assessed the efficacy and adverse effects of primary therapy with early versus deferred androgen suppression therapy in men with advanced prostate cancer. SEARCH STRATEGY: Randomized controlled trials were searched in general and specialized databases (MEDLINE, EMBASE, CancerLIT, Cochrane Library, VA Cochrane Prostate Disease register) and by reviewing bibliographies including those of the Blue Cross and Blue Shield Association Technology Evaluation Center/Evidence-based Practice Center of the Agency for Healthcare Research and Quality (BCBS/TEC-AHRQ) report No.4. SELECTION CRITERIA: All published randomized trials were eligible for inclusion provided they: randomized men with advanced prostate cancer to early versus deferred androgen suppression; reported overall, progression-free, and cancer-specific survival, and/or adverse events; did not utilize androgen suppression as adjuvant therapy to radiation treatment. DATA COLLECTION AND ANALYSIS: An independent reviewer using a standardized form extracted information on trial characteristics, interventions, and outcomes. Results were reviewed for accuracy and discrepancies resolved by discussion. The main outcome measure for comparing effectiveness was the overall survival at 1, 2, 5 and 10 years. Progression-free survival, cancer-specific survival, complications due to disease progression and the incidence of adverse effects of treatment were also measured. MAIN RESULTS: Four trials involving 2,167 patients were included in this review. All of the trials were conducted prior to use of prostate specific antigen (PSA) testing. There was variability between studies regarding the treatments used and the requirements for initiation of treatments. The percent overall survival at 1, 2, 5, and 10 years for the early treatment group was 88%, 73%, 44%, and 18%. For the deferred therapy group the percent overall survival was 86%, 71%, 37%, and 12%. The pooled estimate for the difference in overall survival favored early therapy but was significant only at 10 years when few patients had survived [OR = 1.16 (95% CI: 0.90 to 1.49) at 1 year, 1.08 (95% CI: 0.89 to 1.33) at 2 years, 1.19 (95% CI: 0.95 to 1.50) at 5 years, and 1.50 (95% CI: 1.04 to 2.16) at 10 years]. The pooled estimate of prostate cancer specific survival at 2, 5, and 10 years favored early therapy though the confidence intervals were wide and the results not statistically different. The risk differences at 2, 5, and 10 years were 2.7%, 5.8%, and 4.6%. Although each study used unique definitions of progression free survival, all studies found progression free survival was consistently better in the early intervention group at all time points. Complications due to disease progression were only reported in one study but were more frequent in the deferred treatment group. Adverse events due to treatment were also only reported in one study but occurred more frequently in the early treatment group. REVIEWER'S CONCLUSIONS: The evidence from randomized controlled trials is limited by the variability in study design, stage of cancer and subjects enrolled, interventions utilized, definitions and reporting of outcomes and the lack of PSA testing for diagnostic and monitoring purposes. However, the available information suggests that early androgen suppression for treatment of advanced prostate cancer reduces disease progression and complications due to progression. Early androgen suppression may provide a small but statistically significant improvement in overall survival at 10 years. There was no statistically significant difference in prostate cancer specific survival but a clinically important difference could not be excluded. These outcomes need to be evaluated with the evidence suggesting higher costs and more frequent treatment related adverse effects with early therapy. Additional studies are required to evaluate more definitively the efficacy and adverse effects of early versus delayed androgen suppression in men with prostate cancer. In particular trials should evaluate patients with advanced prostate cancer diagnosed by PSA testing and men with persistent or rising PSA levels following treatment options (e.g. radical prostatectomy, radiation therapy or observation) for clinically localized disease.

Androgen Antagonists↗

PubMed2001

Surgery versus radiotherapy for muscle invasive bladder cancer.

BACKGROUND: Muscle invasive bladder cancer is a serious clinical problem and is fatal for the majority of patients. Alternative treatments for this condition are radical cystectomy or radical radiotherapy. The choice of treatment varies according to the resident country. The ideal treatment would be a bladder preserving therapy with total eradication of the tumour without compromising survival. OBJECTIVES: The objective of this review was to compare the survival after radical surgery (cystectomy) versus radical radiotherapy in patients with muscle invasive cancer. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (July 2000), Medline (July 2000), EMBASE (July 2000), Cancerlit (July 2000), Healthstar (July 2000) and the Database of Abstracts of Reviews of Effectiveness (July 2000). Attempts to contact authors of unpublished data were undertaken. SELECTION CRITERIA: Randomised trials comparing surgery versus radiotherapy were eligible for assessment. DATA COLLECTION AND ANALYSIS: Three reviewers assessed trial quality based on the Cochrane Guidelines. Data was extracted from the text of the article or extrapolated from the Kaplan-Meier plot. The Peto odds ratio was determined to compare the overall-survival and disease-specific survival. Analysis was performed on an intention-to-treat basis and treatment actually received. MAIN RESULTS: Three randomised trials comparing pre-operative radiotherapy followed by radical cystectomy (surgery) versus radical radiotherapy with salvage cystectomy (radical radiotherapy) were eligible for assessment. These trials represented a total of 439 patients, 221 randomised to surgery and 218 to radical radiotherapy. Peto odds ratio analysis consistently favoured surgery in terms of survival. It was significant at 3 (OR = 2.11, 95% CI 1.10,4.07) and 5 years (OR = 2.40, 95% CI 1.35, 4.29) for overall survival and at 3 years (OR = 1.96, 95% CI 1.06,3.65) for disease-specific survival for patients that actually received the protocol treatment. On an intention-to-treat analysis for disease-specific survival, the results were significantly in favour of surgery at 3 years (OR = 1.96, 95% CI 1.06,3.65) but not at 5 years. REVIEWER'S CONCLUSIONS: The evidence from this review suggests that there is no overall statistically significant benefit to radiotherapy or surgery ( with pre-operative radiotherapy) in muscle invasive bladder cancer in terms of survival, but the trends consistently favour surgery.

Confidence Intervals↗

PubMed2001

Interventions for chronic abacterial prostatitis.

BACKGROUND: Chronic abacterial prostatitis is a common disabling but enigmatic condition with a symptom complex of pelvic area pain and lower urinary tract symptoms. The scope of treatments recommended for chronic abacterial prostatitis is a testament to how little is known about what causes the condition and how to treat it. As a result, chronic abacterial prostatitis often causes physician frustration, patient confusion and dissatisfaction, variable thresholds for referral, and potentially inappropriate antibiotic use. OBJECTIVES: Examine the evidence regarding the effectiveness of therapies for chronic abacterial prostatitis. SEARCH STRATEGY: Studies were identified through a search of MEDLINE (1966-2000), the Cochrane Library, bibliographies of identified articles and reviews, and contact with an expert. SELECTION CRITERIA: Studies were eligible if they: (1) are randomized controlled trials (RCTs) or controlled clinical trials (CCTs) (2) involve men with chronic abacterial prostatitis (3) control group receives placebo, sham intervention, active pharmacologic or device therapy for chronic abacterial prostatitis and (4) outcomes data are provided. Eligibility was assessed by at least two independent observers. DATA COLLECTION AND ANALYSIS: Study information on patients, interventions, and outcomes was extracted independently by 2 reviewers. The main outcome was the efficacy of treatment for chronic abacterial prostatitis vs. control in improving urologic symptom scale scores or global report of urinary tract symptoms. Secondary outcomes included changes in the prostate examination, uroflowmetry, urodynamics, analysis of urine, expressed prostatic secretions and seminal fluid, and prostate ultrasonography. MAIN RESULTS: The 15 treatment trials involved: medications used to treat benign prostatic hyperplasia (n=4 trials); anti-inflammatory medications (n=2 trials); antibiotics (n=1 trial); thermotherapy (n=5 trials); and miscellaneous medications (n=3 trials). The disparity between studies did not permit quantitative analysis. There were a total of 600 enrollees (age range 38-45). All but one of the trials were done outside the United States. REVIEWER'S CONCLUSIONS: The treatment trials are few, weak methodologically, and involve small sample sizes. The routine use of antibiotics and alpha blockers for chronic abacterial prostatitis is not supported by the existing evidence. The small studies examining thermal therapy appear to demonstrate benefit of clinical significance and merit further evaluation. Additional treatment trials are required and they should report important patient characteristics (e.g., race), study design details and utilize clinically relevant and validated assessment measures.

Chronic Disease↗

PubMed2000

Allopurinol for chronic prostatitis.

OBJECTIVES: To determine the effects of allopurinol in the treatment of chronic prostatitis SEARCH STRATEGY: Trials were searched in computerized general and specialized databases (MEDLINE, Cochrane Library, Cochrane Prostate Group database), bibliographies of obtained articles, and direct contact with authors. SELECTION CRITERIA: All randomized trials of allopurinol versus placebo used to treat patients with chronic prostatitis. Acute prostatitis, bacterial prostatitis, and asymptomatic prostatitis were excluded. The main outcome measure was the change in patient-reported discomfort. DATA COLLECTION AND ANALYSIS: The reviewers extracted the data independently for the outcomes of change in patient-reported discomfort, investigator graded prostate pain, leukocyte counts, and biochemical indices. MAIN RESULTS: Only one trial with 54 men lasting 240 days (with 330 days of follow-up) met study inclusion criteria. There was a statistically significant change favoring allopurinol in patient-reported discomfort between the study and control groups at follow-up. Between days 45-225, the mean score was -0.95 (s.d. 0.19) for the allopurinol group (7 men), compared with -0.47 (s.d. 0.21) for the placebo group (7 men). The weighted mean difference (WMD) was -0.48 (95%CI -0.690, -0.270). The mean score between days 45-135 was -1.08 (s.d. 1.29) for the 25 men in the allopurinol group, compared with -0.21 (sd 0.97) for the 14 men in the control group. The WMD was -0.87 (95%CI -1.587, -0.153). The allopurinol group had significantly less investigator graded prostate pain and had lower levels of serum urate, urine urate, and expressed prostatic secretion urate and xanthine. No significant differences between the two groups regarding leukocyte counts were found. No patient receiving allopurinol had any significant side effects. Three patients in the placebo group dropped out because of side effects. REVIEWER'S CONCLUSIONS: One small trial of allopurinol for treating chronic prostatitis showed improvements in patient-reported symptom improvement, investigator-graded prostate pain, and biochemical parameters. However, the data provided, the measures used, and the statistics presented do not make these findings convincing that changes in urine and prostatic secretion composition regarding purine and pyrimidine bases resulted in the relief of symptoms. Further studies of allopurinol treatment using standardized and validated outcomes measures and analyses are necessary to determine whether allopurinol is effective.

Allopurinol↗

PubMed2000

Cernilton for benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH), nonmalignant enlargement of the prostate, can lead to obstructive and irritative lower urinary tract symptoms (LUTS). The pharmacologic use of plants and herbs (phytotherapy) for the treatment of LUTS associated with BPH has been growing steadily. Cernilton, prepared from the rye-grass pollen Secale cereale, is one of the several phytotherapeutic agents available for the treatment of BPH. OBJECTIVES: This systematic review aims to assess the effects of Cernilton on urinary symptoms and flow measures in men with benign prostatic hyperplasia (BPH). SEARCH STRATEGY: Trials were searched in computerized general and specialized databases (MEDLINE, EMBASE, Cochrane Library, Phytodok), by checking bibliographies, and by contacting manufacturers and researchers. SELECTION CRITERIA: Trials were eligible if they were: (1) randomized controlled trials or controlled clinical trials comparing Cernilton with placebo or other BPH medications in men with BPH; and (2) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, and outcomes was extracted by at least two independent reviewers using a standard form. Main outcome measure for comparing the effects of Cernilton with placebo and standard BPH medications were the change in urologic symptoms scales. Secondary outcomes included changes in nocturia as well as urodynamic measures (peak and mean urine flow, residual volume, prostate size). Main outcome measure for side effects was the number of men reporting side effects. MAIN RESULTS: 444 men were enrolled in 2 placebo-controlled and 2 comparative trials lasting from 12 to 24 weeks. Three studies used a double-blind method although treatment allocation concealment was unclear in all. Cernilton improved "self rated urinary symptoms" (percent reporting satisfactory or improving symptoms) versus placebo and Tadenan. The weighted risk ratio (RR) for self-rated improvement versus placebo was 2.40 [95% CI = 1.21, 4. 75], and the weighted RR versus Tadenan was 1.42 [95% CI = 1.21, 4. 75]. Cernilton reduced nocturia compared with placebo and Paraprost. Versus placebo, the weighted RR was 2.05 [95% CI = 1.41, 3.00], and versus Paraprost, the WMD was -0.40 times per evening [95% CI = -0. 73, -0.07]. Cernilton did not improve urinary flow rates, residual volume or prostate size compared to placebo or the comparative study agents. Adverse events were rare and mild. The withdrawal rate for Cernilton was 4.8% compared to 2.7% for placebo and 5.2% for Paraprost. REVIEWER'S CONCLUSIONS: The Cernilton trials analyzed were limited by short duration, limited number of enrollees, gaps in reported outcomes, and unknown quality of the preparations utilized. The comparative trials lacked a proven active control. The available evidence suggests Cernilton is well tolerated and modestly improves overall urologic symptoms including nocturia. Additional randomized placebo and active-controlled trials are needed to evaluate the long-term clinical effectiveness and safety of Cernilton.

Humans↗

PubMed2000

Beta-sitosterols for benign prostatic hyperplasia.

OBJECTIVES: This systematic review aimed to assess the effects of beta-sitosterols (B-sitosterol) on urinary symptoms and flow measures in men with of benign prostatic hyperplasia (BPH). SEARCH STRATEGY: Trials were searched in computerized general and specialized databases (MEDLINE, EMBASE, Cochrane Library, Phytodok), by checking bibliographies, and by contacting manufacturers and researchers. SELECTION CRITERIA: Trials were eligible for inclusion provided they (1) randomized men with BPH to receive B-sitosterol preparations in comparison to placebo or other BPH medications, and (2) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, and outcomes was extracted by at least two independent reviewers using a standard form. Main outcome measure for comparing the effectiveness of B-sitosterols with placebo and standard BPH medications was the change in urologic symptom scale scores. Secondary outcomes included changes in nocturia as well as urodynamic measures (peak and mean urine flow, residual volume, prostate size). Main outcome measure for side effects was the number of men reporting side effects. MAIN RESULTS: 519 men from 4 randomized, placebo-controlled, double-blind trials, (lasting 4 to 26 weeks) were assessed. 3 trials used non-glucosidic B-sitosterols and one utilized a preparation that contained 100% B-sitosteryl-B-D-glucoside. B-Sitosterols improved urinary symptom scores and flow measures. The weighted mean difference (WMD) for the IPSS was -4.9 IPSS points (95%CI = -6.3 to -3.5, n = 2 studies). The WMD for peak urine flow was 3.91 ml/sec (95%CI = 0.91 to 6.90, n = 4 studies) and the WMD for residual volume was -28.62 ml (95%CI = -41. 42 to -15.83, n = 4 studies). The trial using 100% B-sitosteryl-B-D-glucoside (WA184) show improvement in urinary flow measures. B-sitosterols did not reduce prostate size. Withdrawal rates for men assigned to B-sitosterol and placebo were 7.8% and 8. 0%, respectively. REVIEWER'S CONCLUSIONS: The evidence suggests non-glucosidic B-sitosterols improve urinary symptoms and flow measures. Their long term effectiveness, safety and ability to prevent BPH complications are not known.

Humans↗

PubMed2000

Serenoa repens for benign prostatic hyperplasia.

OBJECTIVES: This systematic review aimed to assess the effects of Serenoa repens in the treatment of Benign Prostatic Hyperplasia (BPH). SEARCH STRATEGY: Trials were searched in computerized general and specialized databases (MEDLINE, EMBASE, Cochrane Library, Phytodok), by checking bibliographies, and by contacting manufacturers and researchers. SELECTION CRITERIA: Trials were eligible if they (1) randomized men with BPH to receive preparations of Serenoa repens (alone or in combination) in comparison with placebo or other BPH medications, and (2) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements. Eligibility was assessed by at least two independent observers. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, and outcomes was extracted by at least two independent reviewers using a standard form. The main outcome measure for comparing the effectiveness of Serenoa repens with placebo or other BPH medications was the change in urologic symptom scale scores. Secondary outcomes included changes in nocturia and urodynamic measures. The main outcome measure for side effects was the number of men reporting side effects. MAIN RESULTS: 2939 men from18 randomized trials lasting 4 to 48 weeks were assessed. 16 trials were double-blinded and treatment allocation concealment was adequate in 9 studies. Compared with placebo, Serenoa repens improved urinary symptom scores, symptoms, and urinary flow measures. The weighted mean difference (WMD) for the urinary symptom score was -1.41 points (scale range 0-19), (95%CI = -2.52, -0.30, n = 1 study) and the risk ratio (RR) for self rated improvement was 1.75 (95%CI = 1.21, 2.54, n = 6 studies). The WMD for nocturia was -0.76 times per evening (95%CI = -1.22, -0.32; n = 10 studies). The WMD for peak urine flow was 1.93 ml/sec (95%CI = 0.72, 3.14, n = 8 studies). Compared with finasteride, Serenoa repens produced similar improvements in urinary symptom scores (WMD = 0.37 IPSS points (scale range 0-35), 95%CI = -0.45, 1.19, n = 2 studies) and peak urine flow (WMD = -0.74 ml/sec, 95%CI = -1.66, 0.18, n = 2 studies). Adverse effects due to Serenoa repens were mild and infrequent. Withdrawal rates in men assigned to placebo, Serenoa repens or finasteride were 7%, 9%, and 11%, respectively. REVIEWER'S CONCLUSIONS: The evidence suggests that Serenoa repens improves urologic symptoms and flow measures compared with placebo. Serenoa repens produced similar improvement in urinary symptoms and flow compared to finasteride and is associated with fewer adverse treatment events. The long term effectiveness, safety and ability to prevent BPH complications are not known.

Androgen Antagonists↗

PubMed2000

Immunotherapy for advanced renal cell cancer.

BACKGROUND: The course of advanced renal cell carcinoma is extremely variable, ranging from spontaneous remission to disease progression refractory to chemotherapy. Immunotherapy has held promise of improved outcomes based on uncontrolled studies and randomized controlled trials generally limited by small size and low power. OBJECTIVES: To evaluate immunotherapy for advanced renal cell carcinoma by comparing: (1) high dose interleukin-2 to other options and (2) interferon-alpha to other options. SEARCH STRATEGY: A search of MEDLINE, Cancerlit, EMBASE and Cochrane Library databases from 1966 through the end of 1999. Handsearches were made of the proceedings of the annual meetings of the American Urologic Association, ASCO, and biennial European ECCO meetings, and the references of identified studies. SELECTION CRITERIA: Randomized controlled trials that selected (or stratified) patients with advanced renal cell carcinoma, utilized an immunotherapeutic agent in at least one study arm, and reported response or survival by allocation. Forty-two studies involving 4216 patients were eligible and reported response and 26 of these reported survival outcome (3089 patients). DATA COLLECTION AND ANALYSIS: Two independent reviewers abstracted each article by following a prospectively designed protocol. Dichotomous outcomes for treatment response (partial plus complete) and for deaths at one year were used for the main comparisons. Survival hazard ratios were also used for studies of interferon-alpha versus controls. MAIN RESULTS: The average response rate was 10.2 % (range by arm, 0 - 39%) and complete response rate was 3.2% (123/3852; n = 38 studies). Median survival averaged 11.6 months (range by arm, 6 - 28 months) and two-year survival averaged 22% (16 studies, range by arm 8 - 41%). There were no placebo-controlled studies and no randomized controlled studies examined survival for high dose interleukin-2 versus controls. Results from 6 studies (n = 963) indicate that interferon-alpha is superior to controls (OR for death at one year = 0.67, 95% CI 0.50 - 0.89. The pooled hazard ratio for survival of 0.78 (0.67 - 0.90) indicates that the treatment effect persisted until 24 months from randomization. The weighted average median improvement in survival was 2.6 months. Additional comparisons failed to prove a survival benefit from the addition of other agents to either modified schedules of interleukin-2 or to interferon-alpha. Dose-response studies examining survival for either agent could not be identified. The difference in response rate between arms was correlated with the difference in survival (P<0.001) suggesting that response rate difference may be a surrogate intermediate endpoint for survival. REVIEWER'S CONCLUSIONS: Interferon-alpha provides a modest survival benefit compared to other commonly used treatments and should be considered for the control arm of future studies of systemic agents. Interleukin-2 has not been validated in controlled randomized studies.

Antineoplastic Agents↗

PubMed2000

Maximal androgen blockade for advanced prostate cancer.

OBJECTIVES: This systematic review assessed the effect of maximal androgen blockade (MAB) on survival when compared to castration (medical or surgical) alone for patients with advanced prostate cancer. SEARCH STRATEGY: Randomized controlled trials were searched in general and specialized databases (MEDLINE, EMBASE, Cancerlit, Cochrane Library, VA Cochrane Prostate Disease register) and by reviewing bibliographies. SELECTION CRITERIA: All published randomized trials were eligible for inclusion provided they (1) randomized men with advanced prostate cancer to receive a non-steroidal anti-androgen (NSAA) medication in addition to castration (medical or surgical) or to castration alone, and (2) reported overall survival, progression-free survival, cancer-specific survival, and/or adverse events. Eligibility was assessed by two independent reviewers. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, and outcomes were extracted by two independent reviewers using a standardized form. The main outcome measure for comparing effectiveness was overall survival at 1, 2, and 5 years. Secondary outcome measures included progression-free survival and cancer-specific survival. The relationship of specific NSAA on outcome was evaluated. Additionally, the incidence of adverse effects was measured. MAIN RESULTS: Twenty trials enrolling 6,320 patients were included. The pooled OR for overall survival was 1.03 (95% CI:0.85 to 1.25), 1.16 (95% CI:1.00 to 1.33), and 1.29 (95% CI:1.11 to 1.50) at 1, 2, and 5 years respectively. Overall survival was only significant at 5 years. The risk difference at 5 years was 0.048 (95% CI:0.02 to 0.077) and NNT at 5 years 20.8. Progression-free survival was improved only at 1 year follow-up (OR=1.38) and cancer-free survival was improved only at 5 years (OR=1.22). Adverse events occurred more frequently in those assigned to MAB and resulted in withdrawal in 10%. Quality of life was measured in only one study favored orchiectomy alone (less diarrhea and better emotional functioning in the first 6 months). REVIEWER'S CONCLUSIONS: MAB produces a modest overall and cancer-specific survival at 5 years but is associated with increased adverse events and reduced quality of life.

Androgen Antagonists↗

PubMed2000

Epidemiology of high-grade prostatic intraepithelial neoplasia.

This review summarizes published data dealing with the prevalence of high-grade prostatic intraepithelial neoplasia (HGPIN) in a variety of prostate tissue samples. Additionally, we have attempted to document the relationship between HGPIN and the pathological parameters of prostate cancer in autopsy and radical prostatectomy specimens. Studies reporting the prevalence of HGPIN in needle biopsies, transurethral resection specimens and radical prostatectomy specimens, and those documenting the lesion in postmortem settings are compared. We also summarize studies in which the distribution and/or extent of HGPIN was correlated with prostate cancer stage, grade and volume. There is significant variation in the reported frequency of HGPIN, particularly in needle biopsy specimens, with a range of 0.8-23.9%. The factors responsible for these discrepancies include the population studied, the limited sample size that needle biopsies represent, diagnostic inconsistencies and, possibly, tissue preparation/staining variables. Because of the important implications a diagnosis of HGPIN carries, there is a pressing need to achieve greater consistency in diagnosing and reporting the lesion. Better targeted educational efforts, including teaching courses, websites with illustrations and the possibility of teleconsultations, are among possible means to attain this goal. Better documentation of the evolution of HGPIN to cancer through clinical follow-up is also recommended.

Biopsy, Needle↗

PubMed1999

Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostate cancer.

OBJECTIVES: With 184,500 new cases and 39,200 deaths anticipated in 1998, prostate cancer is second only to lung cancer in cancer mortality for men. This report is a systematic review of the evidence from randomized controlled trials on the relative effectiveness of alternative strategies for androgen suppression as treatment of advanced prostate cancer. Three key issues are addressed: (1) the relative effectiveness of the available methods for monotherapy (orchiectomy, luteinizing hormone-releasing hormone [LHRH] agonists, and antiandrogens), (2) the effectiveness of combined androgen blockade compared to monotherapy, and (3) the effectiveness of immediate androgen suppression compared to androgen suppression deferred until clinical progression. Outcomes of interest are overall, cancer-specific, and progression-free survival; time to treatment failure; adverse effects; and quality of life. Two supplementary analyses were conducted for each key question: (1) meta-analysis of overall survival at 2 years (questions 1 and 2) and 5 years (questions 2 and 3), and (2) cost-effectiveness analysis. SEARCH STRATEGY: The MEDLINE, CANCERLIT, and EMBASE databases were searched from 1966 to March 1998, and Current Contents to August 24, 1998, for the terms: leuprolide (Lupron); goserelin (Zoladex); buserelin (Suprefact); flutamide (Eulexin); nilutamide (Anandron, Nilandron); bicalutamide (Casodex); cyproterone acetate (Androcur); diethylstilbestrol (DES); and orchiectomy (castration, orchidectomy). The search was then limited to human studies indexed under the MeSH term "prostatic neoplasms" and by the UK Cochrane Center search strategy for randomized controlled trials. Total yield was 1,477 references. SELECTION CRITERIA: We Reports of efficacy outcomes were limited to randomized controlled trials. Phase II studies that reported on withdrawals from therapy and all studies reporting on quality of life were also included. DATA COLLECTION AND ANALYSIS: The systematic review used a prospectively designed protocol conducted by two independent reviewers, with disagreements resolved by consensus. The meta-analysis combined data on overall survival using a random effects model. The cost-effectiveness analysis used a decision analysis model of advanced prostate cancer with health states and transitions derived from the literature and estimates of effectiveness derived from the meta-analysis. The cost-effectiveness analysis is conducted from a societal perspective, consistent with the guidelines of the U.S. Public Health Service Panel on Cost-Effectiveness in Health and Medicine. MAIN RESULTS: Survival after treatment with an LHRH agonist is equivalent to survival after orchiectomy. The available LHRH agonists are equally effective, and no LHRH agonist is superior to the other when adverse effects are considered. Survival may be somewhat lower with use of a nonsteroidal antiandrogen. There is no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade or monotherapy. Meta-analysis of the limited data available shows a statistically significant difference in survival at 5 years that favors combined androgen blockade. However, the magnitude of this difference is of questionable clinical significance. For the subgroup of patients with good prognosis, there is no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. No evidence is yet available from randomized controlled trials of androgen suppression initiated at prostate-specific antigen (PSA) rise after definitive therapy for clinically localized disease. For patients who are newly diagnosed with locally advanced or asymptomatic metastatic disease, the evidence is insufficient to determine whether primary androgen suppression initiated at diagnosis improves outcomes. (ABSTRACT TRUNCATED)

Androgen Antagonists↗