Jack Geller

The effect of finasteride in men with benign prostatic hyperplasia

Background Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction. Methods In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period. Results As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups. Conclusions The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.

Serum prostate-specific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia

OBJECTIVES Prostate-specific antigen (PSA) is produced exclusively in the prostate gland and is currently the most useful clinical marker for the detection of prostate cancer. In this report, we examine whether serum PSA is also a predictor of important benign prostatic hyperplasia (BPH)-related outcomes, acute urinary retention (AUR), and the need for BPH-related surgery. METHODS Three thousand forty men were treated with either placebo or finasteride in a double-blind, randomized study of 4-year duration. Serum PSA was measured at baseline, and baseline prostate volume was measured in a 10% subset of 312 men. Probabilities and cumulative incidences of AUR and BPH-related surgery, as well as reduction in risk of events with finasteride, were calculated for the entire patient population, stratified by treatment assignment, baseline serum PSA, and prostate volume. RESULTS The risk of either needing BPH-related surgery or developing AUR ranged from 8.9% to 22.0% during the 4 years in placebo-treated patients stratified by increasing prostate volume and from 7.8% to 19.9% when stratified by increasing serum PSA. In comparison with symptom scores, flow rates, and residual urine volume, receiver operating characteristic curve analyses showed that serum PSA and prostate volume were the most powerful predictors of spontaneous AUR in placebo-treated patients (area under the curve 0.70 and 0.81, respectively). Finasteride treatment reduced the relative risk of needing surgery or developing AUR by 50% to 74% and by 43% to 60% when stratified by increasing prostate volume and serum PSA, respectively. CONCLUSIONS Serum PSA and prostate volume are powerful predictors of the risk of AUR and the need for BPH-related surgery in men with BPH. Knowledge of baseline serum PSA and/or prostate volume are useful tools to aid physicians and decision makers in predicting the risk of BPH-related outcomes and choosing therapy for BPH.

The Effect of Finasteride in Men with Benign Prostatic Hyperplasia

BACKGROUND Benign prostatic hyperplasia is a progressive, androgen-dependent disease resulting in enlargement of the prostate gland and urinary obstruction. Preventing the conversion of testosterone to its tissue-active form, dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease the action of androgens in their target tissues; in the prostate the result might be a decrease in prostatic hyperplasia and therefore in symptoms of urinary obstruction. METHODS In a double-blind study, we evaluated the effect of two doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12 months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow, prostatic volume, and serum concentrations of dihydrotestosterone and prostate-specific antigen were determined periodically during the treatment period. RESULTS As compared with the men in the placebo group, the men treated with 5 mg of finasteride per day had a significant decrease in total urinary-symptom scores (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than 0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic volume (P less than 0.001). The men treated with 1 mg of finasteride per day did not have a significant decrease in total urinary-symptom scores, but had an increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and an 18 percent decrease in prostatic volume. The men given placebo had no changes in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The frequency of adverse effects in the three groups was similar, except for a higher incidence of decreased libido, impotence, and ejaculatory disorders in the finasteride-treated groups. CONCLUSIONS The treatment of benign prostatic hyperplasia with 5 mg of finasteride per day results in a significant decrease in symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic volume, but at a slightly increased risk of sexual dysfunction.

Monotherapy with a tumor-targeting mutant of Salmonella typhimurium cures orthotopic metastatic mouse models of human prostate cancer

Bacterial infection occasionally has a marked therapeutic effect on malignancies, as noted as early as the 19th century. Recently, there have been attempts to develop cancer treatment by using tumor-targeting bacteria. These treatments were developed to deliver therapeutic molecules specifically to tumors. Researchers used anaerobic microorganisms that preferentially grew in necrotic tumor areas. However, the resulting tumor killing was, at best, limited. We have developed a far more effective bacterial cancer therapy by targeting viable tumor tissue by using Salmonella typhimurium leu-arg auxotrophs. Although these bacteria grow in viable as well as necrotic areas of tumors, the nutritional auxo trophy severely restricts growth in normal tissue. In the current study, we measured the antitumor efficacy of the S. typhimurium A1-R mutant, which is auxotrophic for leu-arg and has increased antitumor virulence selected by tumor passage. A1-R was used to treat metastatic PC-3 human prostate tumors that had been orthotopically implanted in nude mice. GFP was used to image tumor and metastatic growth. Of the 10 mice with the PC-3 tumors that were injected weekly with S. typhimurium A1-R, 7 were alive and well at the time the last untreated mouse died. Four A1-R-treated mice remain alive and well 6 months after implantation. Ten additional nontumor-bearing mice were injected weekly to determine the toxicity of S. typhimurium A1-R. No toxic effects were observed. The approach described here, where bacterial monotherapy effectively treats metastatic prostate tumors, is a significant improvement over previous bacterial tumor-therapy strategies that require combination with toxic chemotherapy.

The Clinical Effects of a 5α-Reductase Inhibitor, Finasteride, on Benign Prostatic Hyperplasia

AbstractFinasteride (Proscar—an orally active 5α -reductase enzyme inhibitor) blocks the conversion of testosterone to dihydrotestosterone. The effects of finasteride in patients with benign prostatic hyperplasia were investigated in 2 double-blind, placebo-controlled studies. In study 1, 86 patients were treated with placebo or finasteride (5 to 80mg. per day) for 12 weeks, followed by a 12-week drug-free period. After 12 weeks of treatment all doses of finasteride showed significant decreases in prostate volume. However, 12 weeks after discontinuation of finasteride prostate volume returned to near baseline values. In study 2, 104 patients were treated with placebo or finasteride (0.2 to 40mg. per day) for 24 weeks. After 24 weeks of finasteride treatment prostate volume showed a mean decrease of 24% and 28% (p <0.01) in the 1 and 5mg. groups, respectively. Lower doses had a lesser effect on prostate shrinkage. Maximum urinary flow showed a mean increase of 3.7cc per second when the 1 and 5mg. groups we...

Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture

There is strong epidemiological evidence that prostate disease is significantly less prevalent in the Orient, where the intake of soy products is very high, than in the United States. We therefore undertook a study of the effects of genistein, a major component of soy, on growth of human‐patient benign prostatic hypertrophy (BPH) and prostate cancer tissue in three‐dimensional collagen gel‐supported histoculture.

Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia

OBJECTIVES To summarize the 6-year clinical trial data with finasteride. Benign prostatic hyperplasia is a chronic and progressive disease and therefore assessment of long-term safety and efficacy is important. METHODS The North American and International Phase III Finasteride trials enrolled symptomatic men with enlarged prostate glands. The initial 1-year placebo-controlled study was followed by a 5-year open-label extension. In total, 6-year finasteride data were available in 487 patients originally randomized to finasteride, and 5-year data were available on 238 patients originally randomized to placebo. RESULTS After 6 years of treatment with finasteride 5 mg, the mean quasi-American Urological Association Symptom Score improved by 4.0 points, the median prostate volume decreased by 24%, and the mean maximal urinary flow rate increased by 2.9 mL/s (P <0.001 for all parameters). Long-term finasteride treatment was well tolerated, with a low incidence of drug-related sexual adverse events occurring during the first year and even fewer occurrences during the 5-year open extension. CONCLUSIONS Treatment with finasteride leads to durable improvement in urinary tract symptoms, flow rate, and prostate volume, with no increase in the prevalence of drug-related adverse events over time.

Surgical orthotopic implantation allows high lung and lymph node metastatic expression of human prostate carcinoma cell line PC-3 in nude mice

Prostate cancer is the second leading cause of male death in the United States. When diagnosed, nearly half the cases have metastatic lesions. An animal model of human prostate cancer demonstrating spontaneous metastasis from the orthotopic site after tumor implantation should be of great help for us to understand the disease and to formulate treatment strategy. We report here a high metastatic model of human prostate cancer PC‐3.

Proscar: five-year experience

We assessed the long-term safety and efficacy of finasteride, an orally active 5 alpha-reductase inhibitor, in 2 previously reported groups of patients with symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging, and the maximum urinary flow rate was assessed noninvasively. Symptoms were scored utilizing a patient self-administered symptom score questionnaire. Total symptom scores ranged from 0 (or asymptomatic) to 35 (severely symptomatic). After an initial double-blind period, the patients in study 1 were treated with 10 mg finasteride for 1 year and then switched to 5 mg finasteride for an additional 4 years, whereas patients in study 2 were treated with 5 mg finasteride for the entire 5 years. A total of 190 patients were randomized in the double-blind studies, 156 entered year 1 of the open extension and 70 patients completed 5 years of finasteride therapy. In both studies prostate volume was reduced from baseline by 30%, dihydrotestosterone was reduced by 72%, and the maximum urinary flow rate improved by approximately 1.5 ml/s. Prostate-specific antigen was decreased by approximately 50%. Finasteride was well tolerated; approximately 10% of patients reported sexual adverse experiences during the 5-year study period, which were considered drug related by the investigators. The incidence in reporting sexual adverse experiences did not increase with the increased duration of treatment: findings consistent with previous reports. In summary treatment of BPH with finasteride for 5 years inhibits the progression of the disease with an excellent safety profile and represents a low-risk medical option for the treatment of symptomatic BPH.

Treatment of advanced cancer of prostate with megestrol acetate

Abstract Twenty patients (16 Stage D, 4 Stage C) with prostatic cancer were treated with megestrol acetate (Megace), 160 mg. daily. Of 9 previously untreated patients, 4 had partial objective regressions (average time fourteen months to date), 4 became objectively stable (average 11.5 months), and one showed objective progression of his disease on megestrol. Among 11 patients in relapse after hormonal and/or castration therapy, one showed partial objective regression for sixteen months, 8 became objectively stable for an average of 6.8 months, and 2 showed objective progression. Bone scans either improved (40 per cent) or were stable (60 per cent) in previously untreated patients who had partial objective regression or who were objectively stable on inegestrol. Serial bone scans showed progression of disease in all previously treated patients for whom this study was available. Increased prostatic acid phosphatase decreased to normal and remained within the normal range thereafter in 4 of 6 patients in the previously untreated group; plasma testosterone fell significantly in all patients over the first two months but “escaped” toward or into the normal range in many patients after,four to six months; plasma DHeA sulfate remained significantly decreased over a twelve to eighteen-month period of observation. Since megestrol appears to be effective therapy for previously untreated prostatic cancer and since it does not cause gynecoinastia, salt retention, or thromboembolism, it should be studied further as a possible first line drug in the treatment of Stage D prostatic cancer.