AUA 2002 Press Releases

ORLANDO - May 25, 2002 - In the future, it may be possible to provide patients with prostheses generated using their own tissue rather than synthetic material, according to new research from Boston Children's Hospital. Three separate studies focusing on using tissue-engineering techniques to grow personalized tissue for prosthetic use will be presented during the 97th Annual Scientific Meeting of the American Urological Association, to be held from May 25 to 28 in Orlando.

In three separate studies, researchers were able to use tissue-engineering techniques to grow testosterone-releasing testicular prostheses, penile cartilage rods and penile corpora cavernosa in animal models. Data from each of the three studies was promising, showing structural integrity and function in each prosthesis.

The studies, headed by Anthony Atala M.D., on of the world's leading stem-cell researchers, are important because the techniques they employ have the potential to change the way prostheses are developed and utilized. Today's prostheses, normally crafted from silicone or other synthetic materials, have serious risks of extrusion, infection, material breakdown or rejection. Using the patient's own tissue to generate new lessens the chance of serious complication.

"Engineering creates personalized tissue," Atala said. "We take a biopsy from the tissue, grow the cells out and create the prosthesis. Because it's the patient's own tissue, there is no chance of rejection."

The AUA will present a "Meet the Expert" session with Dr. Atala on Tuesday, May 28 at 3 p.m. in the AUA Press Suite in the Orange County Convention Center in Orlando. The three studies will be presented during separate sessions during the meeting on the following dates:

"Penile Corpora Cavernosa Replacement Using Tissue-Engineering Techniques"
Monday, May 27, during a poster session at 10 a.m.

"Physical Characteristics of Tissue-Engineered Prosthesis for the Treatment of Erectile Dysfunction"
Tuesday, May 28, during an unmoderated poster session starting at 7:00 a.m.

"Tissue-Engineered Testicular Prostheses with Prolonged Testosterone Release"
Tuesday, May 28, during a poster session at 10 a.m.

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VARDENAFIL IMPROVES EVEN SEVERE ERECTILE DYSFUNCTION

ORLANDO - May 25, 2002 -Vardenafil significantly improved erectile function (EF) in men suffering from erectile dysfunction (ED), regardless of the origin or baseline severity of their condition, according to a new study conducted by Craig Donatucci, M.D., urologist in practice at the Duke University Medical Center in Durham, NC. His findings will be presented at the American Urological Association Annual Scientific Meeting on May 27 at 2:20 p.m. during a podium session.

The 12-week phase IIb trial consisted of two randomized, double-blind trials of 1,357men, ages 18 or older, suffering from ED for longer than six months to analyze efficacy and safety of the drug. The primary efficacy variable, using the International Index of Erectile Function (EF Domain) was analyzed within subgroups defined by etiology - the origin of ED - and baseline severity defined from EF domain score.

Regardless of dose, vardenafil significantly improved ED, irrespective of etiology or severity.

The phase III trial of vardenafil will be a pivotal study to prove its the efficacy and safety. Adverse effects were dose-related (five, 10 or 20 milligram, or placebo) and were mostly mild to moderate in intensity, including headache, vasodilation, rhinitis, dyspepsia and acid reflux.

"Erectile dysfunction arises from multiple etiologies and manifests from mild to severe," Donatucci said. "In the trial, vardenafil significantly improved erectile dysfunction and was well tolerated by trial participants. It could be yet another option to effectively treat this condition."

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UNIVERSITY OF MARYLAND UROLOGIST GIVE HOPE TO MEN WHO INITIALLY FAIL TO RESPOND TO SILDENAFIL CITRATE.

ORLANDO, Fla., May 25, 2002 - Urologists at the University of Maryland Medical Center have developed a simple strategy to restore normal sexual function to many men who initially fail to respond to sildenafil (Viagra) therapy.

In a study of 253 men, University of Maryland urologists found that with clear instruction on how and when to use the medicine, proper dosing levels and information about the drug's safety, about 40 percent of the men could achieve the desired results. All of the men studied had been prescribed sildenafil citrate by their primary care physicians to correct erectile dysfunction, but it had not helped.

The University of Maryland urologists will describe the results of their study today (May 25) at the American Urological Association's scientific meeting in Orlando, Florida.

"Our findings give hope to men who tried sildenafil citrate, but concluded it wouldn't work for them," says one of the authors of the report, Geoffrey N. Sklar M.D., a urologist at the University of Maryland Medical Center and associate professor of surgery at the University of Maryland School of Medicine.

Erectile dysfunction is the inability to achieve or maintain an erection. Some men experience chronic, complete erectile dysfunction (impotence) while others achieve only partial or brief erections. The condition has many causes, most of which are treatable, and is not an inevitable consequence of aging.

The study followed 253 men who were referred to the urologists after they had tried sildenafil citrate but did not respond. On their first visit, patients were asked to fill out a standard diagnostic questionnaire, the Sexual Health Inventory for Men. They also viewed a brief instructional videotape about erectile function and were given handouts with statements about the safety of sildenafil citrate and instructions on how to use it.

Each patient then spent an average of 12 minutes with the urologist for an examination and a review of their medical history to look for risk factors and conditions that might rule out the use of sildenafil citrate. Patients who could safely take the drug left the office with samples of sildenafil citrate and a prescription.

The urologists found that 17 of the men should not have been prescribed sildenafil citrate in the first place, because they were using either nitroglycerine tablets or patches, or had cardiac or liver contraindications. Of the 236 remaining patients, 98 of them, or 41.5 percent, responded successfully to the sildenafil citrate after the visit. These men were followed for about two years after their initial referral.

Dr. Sklar says many of these men were anxious about their situation. They may not have listened closely when their doctor first told them how to use the drug, or the instructions may have been inadequate. --MORE--

"Some of the men had taken the sildenafil citrate after a heavy meal, which interferes with the absorption of the medication. Others took the wrong dose, or they expected results too soon after taking the pill. Still others overlooked the role of sexual stimulation in providing an erection. And some men gave up on the drug after trying it just one time," says Dr. Sklar

An instruction sheet, developed by Dr. Sklar, tells the patient to take the pill approximately one hour prior to sexual stimulation, on an empty stomach or after a low fat meal. It also advises avoiding alcohol consumption and trying the pill multiple times. The sheet concludes, "Show this information and instructions to your sexual partner."

Dr. Sklar says in 1999, when the study began, sildenafil citrate packaging did not contain detailed recommendations on how to use the drug effectively. Many of the instructions used in the Baltimore study are now included in the new sildenafil citrate packaging, according to Dr. Sklar.

Proper dosing is also important. In this study, 31 percent of the patients responded to the standard first dose of 50-milligrams (mg). But 69 percent of the men required a 100-mg dose to elicit a response. The study also found that the typical patient needed to try sildenafil citrate six-to-eight times before the maximum effect was achieved.

At a mean follow-up of 22 months, 91 percent of the men continued to respond to the medication. Those who did not respond required additional therapies, such as injections, vacuum pumps or surgery to correct their dysfunction.

Dr. Sklar says the study indicates that doctors can help more patients by simply providing some educational materials. He adds that early diagnosis of erectile dysfunction can lead to a better response to sildenafil citrate. The best response came from patients whose dysfunction had persisted for less than two years.

Michael J. Szostak, M.D. a urology resident at the University of Maryland Medical Center, assisted Dr. Sklar in the study, which was not funded by any pharmaceutical company.

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STUDY SHOWS NEW INVESTIGATIONAL DRUG TADALAFIL SUCCESFULLY TREATED ERECTILE DYSFUNCTION UP TO 36 HOURS AFTER DOSING

ORLANDO - May 25, 2002 - A study of the investigational drug tadalafil, a new oral PDE5 inhibitor, found that it increased intercourse success in men with erectile dysfunction (ED) at up to 36 hours after dosing. The study was conducted by Dr. Hartmut Porstclinical investigator in private urological practice in Hamburg, Germany and the international tadalafil study group. He will present the findings at the American Urological Association annual meeting on May x.

In the study, 348 men with mild to severe ED were given either tadalafil 20-mg or placebo. Patients were asked to attempt intercourse on four separate occasions: once 24 hours after a dose, once again 24 hours after a dose, once 36 hours after a dose, and once again 36 hours after a dose

Tadalafil significantly increased the percentage of successful intercourse attempts at 24 hours (57 percent) and 36 hours (60 percent) post dose compared with placebo (31 percent and 30 percent, respectively). Secondary measures of efficacy -- penetration ability, hardness of erection, overall satisfaction - showed tadalafil to have greater efficacy than placebo at both 24 hours and 36 hours post dose.

Tadalafil was well tolerated; headache, flushing and dyspepsia (upset stomach) were the most common side effects, but most were mild to moderate in intensity. The extended duration of effectiveness did not appear to increase the rate of side effects or their severity, and very few patients receiving placebo or tadalafil discontinued due to side effects.

"We are very pleased to see that tadalafil allowed a majority of men in this trial to achieve normal sexual functioning at up to 36 hours after taking the drug," said Dr. Porst. "The extended duration of responsiveness may help eliminate the need for planning sexual intimacy and could potentially set new expectations in the treatment of ED."

Erectile dysfunction is the consistent inability to attain or sustain an erection adequate for satisfactory sexual intercourse. It is estimated to affect more than 30 million men in the United States.

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SCREEN DETECTED PROSTATE CANCERS DEMONSTRATE MORE FAVORABLE OUTCOMES THAN CLINICALLY DIAGNOSED

ORLANDO - May 25, 2002 - Prostate cancers detected through a variety of screening methods posted more favorable prognostic factors than a control group of clinically diagnosed cancers, according to a study conducted by Ingrid W. van der Cruijsen-Koeter. Dr. van der Cruijsen-Koeter will present the findings at the American Urological Association annual meeting on May 26 during a poster session beginning at 3:30 p.m.

In the study of 35,149 men between the ages of 55 and 74, a randomized section was screened via PSA testing, digital rectal examination, transrectal ultrasound and, if indicated, sextant biopsies. To determine the cancers diagnosed in the control arm, a yearly linkage was performed with the database of the Comprehensive Cancer Registry. By using standardized forms and reviewing the patients' charts at the hospital, items related to prostate cancer management were stored.

In the screening arm, 3,481 biopsies were performed and 818 prostate cancers were detected. In the control arm, 150 prostate cancers were diagnosed. The most striking result is a more favorable stage and grade in the screen arm with more metastasis in the control arm.

"The differences in the number of metastasized prostate cancers, lower grading and less endocrine therapy could well be potential indicators for a positive effect on screening for prostate cancer," said Dr. van der Cruijsen-Koeter.

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UNIVERSITY OF PITTSBURGH RESEARCHERS USE BOTOX TO TREAT OVERACTIVE BLADDER

ORLANDO, Fla., May 25, 2002 - Botulinum toxin A (BTX) injections, commonly known as Botox, show promise as a treatment for a variety of lower urinary tract dysfunctions, according to a study presented by University of Pittsburgh researchers at the 97th Annual Scientific Meeting of the American Urological Association (AUA). Results will be published in abstract 98 in the AUA proceedings.

"Bladder dysfunction affects a staggering number of people worldwide. The use of Botox injections can offer many of these patients a safe, but temporary, solution to this embarrassing problem," said Michael Chancellor, M.D., professor of urology and gynecology at the University of Pittsburgh School of Medicine.

In the study, 50 patients were injected with BTX into the bladder or urethra. Patients suffered from a variety of voiding dysfunctions, including multiple sclerosis, spinal cord injury, stroke, overactive bladder, and interstitial cystitis (IC). Each experienced involuntary contractions of the bladder muscle, which either caused incontinence typified by either uncontrolled voiding of urine or the inability to completely empty the bladder.

Forty-one of the 50 patients, or 82 percent, reported a decrease or absence of incontinence after the injections. The decrease was seen within seven days of the injection and symptoms were alleviated for approximately six months. None of the patients experienced long-term complications to the treatment such as stress incontinence or urinary retention.

BTX acts by binding to the nerve endings of muscles, blocking the release of the chemical that causes the muscle to contract. When injected into specific muscles, the muscle becomes paralyzed or weakened, but leaves surrounding muscles unaffected, allowing for normal muscle function.

Common urologic conditions like neurogenic detrusor hyperreflexia and overactive bladder are caused by involuntary contractions of the detrusor muscle, which controls the bladder. This new therapy helps alleviate the contractions, restoring normal bladder function.

Over 17 million Americans suffer from overactive bladder, a condition that significantly affects the patient's quality of life. An estimated 80 percent of these patients do not seek help or treatment for this condition. Overactive bladder is characterized by the following conditions: frequency, urinating more than eight times in a 24 hour period; urgency, the immediate and strong urge to urinate; and urge incontinence, the inability to suppress urgency resulting in the leaking or loss of urine.

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MUSCLE DERIVED CELL TRANSPLANTS MAY OFFER AN ALTERNATIVE TO TRADITIONAL INCONTINENCE THERAPIES SAY UNIVERSITY OF PITTSBURGH RESEARCHERS

ORLANDO - May 25, 2002 - Researchers from the University of Pittsburgh School of Medicine have found that, in animal models, autologous skeletal muscle derived cell (MDC) transplants offer a safer, more effective and longer lasting treatment for urinary incontinence than existing methods. In the procedure, muscle cells are taken from the individual, purified and cloned, and then reinjected into the bladder.

"In patients who need more advanced treatments for incontinence, we currently have the options of treating them through surgery or through the injection of bulking agents like collagen. Although collagen injections give good short-term results and are less invasive than surgery, there is a possibility of the collagen being reabsorbed or causing allergic reactions," said Ryan J. Pruchnic, of the departments of urology and orthopaedic surgery, University of Pittsburgh School of Medicine and lead author of the study. "In our study, MDCs have the potential to offer a longer-term solution without the risk of rejection."

Pruchnic and colleagues presented these findings today at the Centennial Celebration Annual Meeting of the American Urological Association (AUA). Results are published in abstract 131 in the AUA proceedings.

In the study, researchers obtained a mixed population of MDCs from a mouse skeletal muscle biopsy. The cells were purified to obtain a population that was purely myogenic - meaning that the cells were from muscle and capable of producing muscle. One cell from this population was then genetically engineered and cloned to form a large population. These cells were then injected into the bladder walls of mice.

The bladders of the mice were evaluated at one, four and eight weeks and 6 months. On evaluation, researchers noted the presence of myofibers, or differentiated muscle cells, throughout the smooth muscle layer, the number of which did not significantly decrease over time. Some of the myofibers expressed ?-smooth muscle actin, suggesting differentiation of the cells into smooth muscle. Researchers also observed the presence of neuromuscular junctions, indicating that the muscle was supplied with nerves giving the muscle the ability to become functional tissue.

"These findings indicate that the use of MDCs may prove to be a very promising new therapy in the treatment of urinary incontinence. Essentially, we are giving the bladder muscles the ability to fix themselves by generating new muscle," said Michael Chancellor, M.D., professor of urology and gynecology at the University of Pittsburgh School of Medicine. "In future studies we hope this will turn into a long lasting, if not permanent, solution for our patients."

Urinary incontinence affects 13 million Americans and is typified by the inability to control the flow of urine. Incontinence can be caused by a number of different anatomic, physiologic, and pathologic factors and can be temporary or chronic. The ability to control bladder function relies on the combined function of the smooth muscle tissue of the urethra and bladder, skeletal muscle and the nervous system.

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YOUNG CIGARETTE SMOKERS WITH PROSTATE CANCER HAVE MORE AGGRESSIVE DISEASE

ORLANDO - May 25, 2002 - Cigarette smoking is linked to aggressive forms of prostate cancer, according to a new study, conducted by William W. Roberts with the Brady Urological Institute at Johns Hopkins Hospital. Dr. Roberts will present the findings at the American Urological Association Annual Scientific Meeting during a poster session on May 26 at 10 a.m.

The study included 498 men who underwent radical prostatectomy before age 55 between 1992 and 1999. A survey soliciting cigarette smoking history and other exposures was mailed, yielding a response rate of 73 percent.

Of the respondents, 5.4 percent were current smokers and 44.6 percent were former smokers at the time of surgery. Findings show the risk of extra-prostatic and high-grade/extra-prostatic disease heightened with increased cumulative years of cigarette smoking. This association was pronounced when evaluating cumulative smoking in the 10 years prior to prostate cancer diagnosis.

"Cigarette smoking, in particular a recent smoking history, may influence the risk of aggressive prostate cancer in young men," Dr. Roberts said. "One of the early and most consistent features of prostate cancer is loss of GSTP1, a scavenger enzyme known to detoxify carcinogens in cigarette smoke. Thus if this enzyme is knocked out in men with prostate cancer, one could imagine how cigarette smoking could aggravate genomic damage."

Cigarette smoking is a risk factor for several common chronic diseases although it has not been widely believed to influence prostate cancer.

Dr. Roberts believes physicians and health educators are unlikely to discuss prostate cancer when counseling patients and the public about the risks of cigarette smoking, therefore the findings are important from a scientific, clinical and public health perspective.

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AGE INCREASE, DIABETES SIGNIFICANTLY ASSOCIATED WITH ERECTILE DYSFUNCTION

ORLANDO - May 25, 2002 - The first nationally representative study of erectile dysfunction (ED) showed the prevalence was significantly associated with increasing age and with diabetes, according to a new study conducted by Culley C. Carson, M.D., professor at the University of North Carolina, Chapel Hill. His findings will be presented at the American Urological Association Annual Scientific Meeting on May 25 in a podium session started at 4:00 p.m.

This is the first nationally representative cross-sectional study of ED among men ages 40 and older, with no upper age limit. It was designed to determine age-specific ED prevalence in black, white and Hispanic men, and to evaluate the associations between ED and other comorbidities.

The five-month study used a list-assisted, random-digit dialing design to obtain a nationally representative sample of in 134 non-Hispanic black, 491 non-Hispanic white and 195 Hispanic men. Computer-assisted telephone interviews collected non-sensitive information, such as demographics and medical history, while an automated telephone self-interview collected sensitive information on sexual habits.

The results showed that 49, 29, 14 and eight percent of men reported they were "always," "usually," "sometimes," or "never" able to keep a satisfactory erection for sexual intercourse, respectively. Those who answered "sometimes" or "never" were labeled as having ED.

ED prevalence increased with age: eight percent, ages 40 to 49; 19 percent, ages 50 to 59; and 39 percent, ages 60 and older. ED was also associated with diabetes - an odds ratio of 2.1 - but not associated with ischemic heart disease, high cholesterol or hypertension in this analysis.

"Erectile dysfunction is a common problem - 22 percent of those interviewed reported having the condition," Carson said. "Although further testing is needed to more accurately determine the relationship between age, diabetes and erectile dysfunction, this study gives us a preview of what we will find."

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MINIMALLY INVASIVE TREATMENT FOR ENLARGED PROSTATE REMAINS SUCCESSFUL AT FIVE-YEAR CHECKPOINT

ORLANDO - May 25, 2002 - Cooled thermotherapy (TUMT) using the Targis system for treatment of an enlarged prostate has shown excellent four- and five-year post-treatment results, according to a new study conducted by Steven A. Kaplan, M.D., professor of urology, vice chairman and administrator, department of urology at Columbia University in New York.

TUMT is a specially designed microwave catheter that heats the prostate and cools the urethra simultaneously. A computer-generated treatment algorithm to maintain accurate temperatures monitors the process.

Patients were monitored for five years and were evaluated using validated questionnaires. Responses showed that their symptoms and quality of life improved while flow rates (speed of urination) remained durable.

The test group included 345 TUMT-treated patients, ages 45 to 85. Patients had the following similarities: enlarged prostate, peak flow rates of 12 milliliters per second or less - considered significantly impaired - and American Urological Association (AUA) symptom score of nine or greater. The AUA symptom score is the outcome of a series of urination function questions (35 is the highest score, representing the most severe symptoms).

They collected quality of life scores each year and evaluated peak flow rates for the first three years following treatment. For various reasons, 52 patients dropped out of the study.

Of the remaining patients, AUA symptom scores improved each year (49, 45, 45, 39 and 41 percent from the first to fifth year, respectively. Peak flow rates improved 60 percent the first, 55 percent the second and 48 percent the third year.

A total of 29 percent of the patients have undergone re-treatment, while the Kaplan-Meier survival curves show patients free from subsequent alternative treatment are 93, 84, 75, 68 and 60 percent at the one, two, three, four and five year marks, respectively. Little U.S. long-term data exists on the efficacy of this treatment.

"Benign prostatic hyperplasia, or an enlarged prostate, is a problem affecting eight to nine million men in the United States," Kaplan said. "We will continue to follow these patients for long-term results. As of now, this study shows promise for the efficacy of cooled thermotherapy using the Targis system."

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ERECTILE DYSFUNCTION PREDICTS HEART DISEASE

ORLANDO - May 25, 2002 - Erectile dysfunction is a strong indicator of future forms of ischemic heart disease, according to a study conducted by Dr. Francesco Montorsi at the University Vita - Salute, Scientific Institute H. San Raffaele in Milan. He will present his findings at the American Urological Association's Annual Scientific Meeting during a poster session on May 27, 2002, starting at 10:00 a.m.

In the study, 300 patients with sudden severe chest pain (mean age: 61 years; range: 37-83) were admitted to the heart intensive care unit and underwent a morphological and functional evaluation of the coronary arteries through a coronary angiography. The patients then completed a detailed general and sexual history questionnaire, as well as the Beck's inventory for depression and the AUA Symptom Score, among others.

The study showed a high prevalence of erectile dysfunction in ischemic heart disease patients. In addition, a significant rate of patients developed erectile dysfunction at a mean of 53.4 months prior to developing ischemic heart disease.

"The preliminary data in this report still need confirmation in a larger patient population, but the study does raise the issue of erectile dysfunction as a predictive factor for ischemic heart disease in some patients," said Montorsi. "Reasons may be related to the fact that in the vast majorities of cases, erectile dysfunction develops due to abnormalities of blood circulation: as penile blood vessels are very small and more prone to become abnormal when vascular risk factors like aging, smoking, diabetes and high cholesterol are present, impaired erections may show up much earlier than symptoms of poor circulation coming from other parts of the body such as the heart."

Erectile dysfunction patients with vascular risk factors may consider being seen by their physician for a general vascular evaluation. This study was supported by an unrestricted grant by Pfizer Italy.

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ETHNICITY, SOCIODEMOGRAPHICS A PREDICTOR FOR PROSTATE CANCER RECURRENCE AFTER PROSTATECTOMY

ORLANDO - May 25, 2002 -Ethnicity appears to be a predictor of outcome for patients with prostate cancer who choose radical prostatectomy, but sociodemographic differences - rather than a more-aggressive tumor phenotype -- may be responsible for poorer outcomes in African-American men, according to new research being presented at the 97th Annual Scientific Meeting of the American Urological Association in Orlando. The study - which includes data from the CaPSURE database and the University of California, San Francisco - will be presented during a moderated poster session on May 26, 2002. A representative from the group will participate in a press briefing on May 27 at 1 p.m.

Researchers from the University of California, San Francisco (UCSF) studied 1,468 patients who either underwent radical prostatectomy at UCSF or were registered in CaPSURE, a longitudinal disease registry of patients with prostate cancer. CaPSURE has been sponsored by TAP Pharmaceutical Products Inc since 1995, and is managed by the UCSF Urology Outcomes Research Group. For each patient, preoperative characteristics - such as age, race, prostate-specific antigen level at diagnosis, biopsy Gleason score, clinical tumor stage and percent positive prostate biopsies at diagnosis - were determined. Patients were assigned to risk groups based on stage, PSA at diagnosis and biopsy Gleason score. Using the Kaplan Meier method, the likelihood of disease recurrence for each group was determined and compared using the log-rank test.

Disease recurred in 304 patients, and on analysis, African-American ethnicity, serum PSA at diagnosis, biopsy Gleason score and percent positive biopsies were independent predictors of recurrence. According to the researchers, ethnicity was most important for the high-risk group, where estimated five-year disease-free survival was 65 percent for Caucasians and 28 percent for African Americans.

Traditionally, researchers have believed that African-American men have poorer outcomes for prostate cancer because in many cases, they present with more advanced disease. Like many malignancies, prostate cancer is most treatable when caught early. Differences in quality of care and attitudes toward screening have been linked to outcome differences between the races.

However, after affirming race as an independent variable for recurrence, researchers then re-analyzed the data, adjusting for sociodemographic factors, including education level and household income, in addition to ethnicity. The results demonstrated that the differences in recurrence rates between African-American men and Caucasian men appear to be linked to socioeconomic differences between ethnic groups.

"What these data suggest is that the difference between African-American men and Caucasian men may be socioeconomic in origin," said Gary D. Grossfeld, a researcher on the study. "We feel this is a springboard for a larger body of research."

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LONG-TERM TREATMENT OF AGE-RELATED ERECTILE DYSFUNCTION USING GENE THERAPY

ORLANDO - May 25, 2002 - A single injection of naked human maxi-K gene into penile smooth muscle chronically reversed the effects of aging for up to six months in a rat model and may be successful in the long-term treatment of age-related erectile dysfunction, according to new research from the Albert Einstein College of Medicine in New York. Arnold Melman, M.D. will present the study during an unmoderated poster session on Tuesday, May 28.

Researchers used 191 rats in the study, which were given either phosphate buffered saline, 1000 ng vector or 10, 100 or 1,000 ng of nSlo/pcDNA using intercavernosal injection. The rats were examined in terminal experiments at monthly intervals from one to six months following injection. Researchers measured intracorporeal pressure in response to nerve stimulation to measure the effect of the therapy.

Data collected showed a significant effect of treatment on erection that correlated with the increased dosage of the gene. In the rats receiving the 100 ng and 1,000 ng. dose, results were sustained for up to six months after a single injection. Researchers also noted that organ systems were not affected by the treatment. The therapy may give physicians a new alternative to treat age-related erectile dysfunction in the future.

Current pharmacological treatments involve the nitric oxide pathway in the muscle, and sustain relaxation. Muscle tone does not decrease, and the effects of aging are not inhibited.

This mode of gene therapy would, in essence, reverse the effect of aging. Membrane-bound potassium channels both initiate and maintain smooth-muscle relaxation, and the injection of the hSlo/Maxi-K gene gives the muscle an extra potassium channel, and allows for a "super-physiologic" response to what is naturally happening, according to Melman.

"The beauty of [injection of Maxi-K] is that the effect only occurs when the body gives the natural signal," he said.

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STUDY FINDS GREEN TEA EXTRACTS USEFUL IN TREATING BLADDER CANCER

ORLANDO - May 25, 2002 - Green tea extracts functioned as a chemopreventive agent on an in vitro bladder cancer model, according to a new study presented by Dr. Allan J. Pantuck with the UCLA School of Medicine's Urology Department. His findings will be presented at the American Urological Association annual meeting during an unmoderated poster session starting at 7:00 a.m. on May 27.

The study found that the green tea extracts known as catechins, which are antioxidants, inhibit bladder cancer cell growth, induce cell differentiation and have a modulateable effect on cellular F/G-actin ratios in both PC and MTC11 cells that suggest that they can decrease malignant transformation.

"The preliminary data suggest that green tea may be an effective agent to prevent smoking-related bladder cancers in patients," said Pantuck. This idea will be further scrutinized when the National Cancer Institute begins a five-year, phase three study at UCLA under the direction of Dr. Arie Belldegrun and Dr. Robert Figlin, from the departments of urology and medicine, to test the benefits of green tea as a treatment for patients with superficial bladder cancer.

The study used an in vitro bladder cancer model consisting of several cell lines, all derived from the same human urothelial clone immortalized by SV-40. The model provided a unique system to test the effect and interaction of chemopreventive agents on the carcinogenicity of 4 Aminobiphenol (4-ABP), the major carcinogenic derivative found in cigarette smoke. The study tested the effects of individual catechins found in commercially available green tea extracts.

Compared to untreated controls, certain cell lines treated with green tea showed a dose-responsive decrease in cell growth and increased cellular differentiation. The study was performed in collaboration with Dr. Zuo-Feng Zhang from the UCLA School of Public Health and with Dr. Jian-Yu Rao from the department of pathology and laboratory medicine.

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STUDY IDENTIFIES COMMON COMPLICATIONS FROM HAND-ASSISTED LAPAROSCOPY DURING UROLOGIC SURGERY

ORLANDO - May 25, 2002 - Minor and major complications can occur during and after hand-assisted laparoscopic surgery (HALS), according to a new study conducted by Sean P. Hedican, M.D., assistant professor of surgery, division of urology at University of Wisconsin-Madison. His findings will be presented at the American Urological Association annual meeting on May 25.

Common minor complications included urinary retention, injury to splenic capsule and prolonged ileus. Common major complications - those significantly impacting usual intraoperative or postoperative course, according to the attending surgeon - included small bowel injury, open conversion to control bleeding (over-sewing or clamping of a bleeding vessel), and reintubation (reinsertion of the breathing tube).

Hedican and others reviewed medical chart data of 196 patients who underwent complicated HALS at three major academic institutions, documenting all complications during and after surgery regardless of the severity. All of the surgeries were renal operations.

A total of 28 patients (14.3 percent) suffered 31 minor complications, five of which were during and 26 after the operation. A total of 18 patients (9.2 percent) suffered 32 major complications, seven of which were during and 25 after the operation.

Eleven patients experienced multiple complications, accounting for 46 percent of the total complications - 68.8 percent of the major and 22.6 percent of the minor complications.

"It is important to know the more common complications of hand-assisted laparoscopic surgery so surgeons can educate and discuss the relevant risks with patients before surgery," said Hedican. "The utility of HALS is supported by the acceptable occurrence of minor or major intraoperative complications during complex laparoscopic procedures."

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STUDY IDENTIFIES COMMON COMPLICATIONS FROM HAND-ASSISTED LAPAROSCOPY DURING UROLOGIC SURGERY

Eleven patients experienced multiple complications, accounting for 46 percent of the total complications - 68.8 percent of the major and 22.6 percent of the minor complications.

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PLCO SCREENING TRIAL DATA INVESTIGATES INTERVALS FOR PROSTATE CANCER SCREENING

ORLANDO - May 25, 2002 - Men with a prostate-specific antigen (PSA) level of less than 1 ng/ml and a normal digital rectal exam (DRE) may not benefit from yearly prostate cancer screenings, according to new research being presented at the 97th Annual Meeting of the American Urological Association in Orlando. The data, from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, will be presented by David Crawford, M.D. during a poster session on Sunday, May 26 starting at 3:30 p.m.

The PLCO Screening Trial is a health study designed to determine whether screening tests for prostate, lung, colorectal and ovarian cancers can reduce deaths related to those diseases. Patients are divided into two groups - one receiving regular screening and the other usual care. The trial includes more than 154,000 men and women aged 55 to 74. For men, PSA is assessed at each of six yearly screening rounds, and DRE is conducted at the first four annual exams.

Using PLCO data, researchers evaluated changes in total PSA over five years for 27,863 men in the screening arm of the trial who had baseline PSA levels of less than 4 ng/ml and at least one subsequent PSA test. Researchers used a statistical model to estimate the probability that PSA would rise to at least 4 ng/ml within five years. A PSA level of 4 ng/ml is considered positive.

Results showed that 98.6 percent of men with a PSA less than 1 ng/ml would remain negative (under 4 ng/ml) after four years of testing, and 98.8 percent of men with a baseline PSA of 1 to 2 ng/ml would have a negative test the following year.

Based on the data, the researchers concluded that if men with a PSA level of less than 1 ng/ml typically received their next PSA test five years later, while men with levels of 1 to 1.9 ng/ml were tested again after two years, there would be a 55 percent decrease in the number of PSA tests, and an annual cost savings of $1 billion.

These results provide a scientific basis for discussion of screening intervals with men who chose PSA screening. They provide no scientific basis for determining the merits of PSA screening, according to Crawford.

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MORE YOUNGER MEN TESTING POSITIVE FOR PROSTATE CANCER

ORLANDO - May 25, 2002 - Increased awareness of prostate cancer and prostate-specific antigen (PSA) testing has led to an increase not only in the number of young men being biopsied but also in the detection rate for the disease, according to new research being presented at the 97th Annual Scientific Meeting of the American Urological Association in Orlando. Hillel Kahane, first author on the study, will present the data in a poster session on May 26, 2002 at 10 a.m.

The authors hypothesize not only that PSA testing has led to an increased evaluation for prostate cancer, but also an increase in detection rates for men aged 50 to 59. More than 311,000 biopsies reviewed at DIANON Systems in Stratford, Conn., between 1995 and 2001 were analyzed according to disease incidence, detection rate and patient age.

Researchers began by reviewing data from the seven-year period and examining incidence rates per year for 311,665 biopsies reviewed by DIANON and found a positive cancer rate of 29.3 percent in 1995, which increased to 33.6 percent in 2001. This increase in positive biopsies was a 15 percent increase from baseline.

In the age group of 50 to 59 years, the detection rate increased from baseline of 11 percent in 1995 to 16 percent in 2001. This was a 45 percent increase in the 50 to 59 age population. For men aged 70 to 79 years, the detection rate fell from 41 percent to 37 percent, a 10 percent decrease.

"An increased detection rate as well as a greater percentage of men being biopsied in the group of younger men compared to other age groups caused this," said Franklin Lowe, M.D., M.P.H., the senior author on the study. "Thus, we're identifying more younger men with prostate cancer."

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SMALL RENAL TUMORS MAY NOT REQUIRE LAPAROSCOPIC, OPEN SURGERY

ORLANDO, May 25, 2002-Computed tomography (CT)-guided percutaneous radiofrequency ablation can be an effective nonsurgical treatment for small renal tumors, according to research being presented during the 97th Annual Scientific Meeting of the American Urological Association in Orlando. Researchers from University of Texas Southwestern will give a video presentation of the procedure on May 25 at 1:00 p.m.

The presentation will report on experiences with six patients undergoing CT-guided radiofrequency ablation of small (less than four centimeters) posterior (back) or lateral (side) renal tumors over the past year. The six procedures had no complications and patients were discharged within 24 hours with no need for pain medication. All four patients with three-month follow-up CT scans showed no evidence of tumor enhancement.

During the procedure, patients lie in the prone position. Urologists - in conjunction with interventional radiologists - insert a probe through the back into the kidney and ablate the tumor using radiofrequency energy. The procedure is considered noninvasive.

"At the end of the procedure, there's a puncture mark that you put a plastic bandage over and the patient is able to go home either the same day or the next morning," said Kenneth Ogan, a researcher on the study. "It's revolutionizing the way we treat these renal tumors."

Initial results have been promising. But, though doctors have been performing noninvasive ablation procedures to treat small tumors for years, Ogan points out a need for more extensive follow up.

"The short term results are very good," he said. " "But, with any cancer procedure, you need long-term results to confirm treatment efficacy."

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RHO-KINASE INHIBITOR IMPROVES ERECTILE RESPONSE IN RATS WITH HIGH BLOOD PRESSURE

ORLANDO - May 25, 2002 - Y-27632, an experimental drug known for its ability to lower blood pressure, improved sexual function in a hypertensive rat model, according to researchers from the University of California, San Diego. The results will be presented during the 97th Annual Scientific Meeting of the American Urological Association in Orlando.

The study is important because it explores a new pathway for treating erectile dysfunction (ED). In order to achieve erection, the smooth muscles in the penis must relax. Rho-kinase is an enzyme that activates contractile pathways in the penile smooth muscles - decreasing relaxation of the muscle. By inhibiting this enzyme with Y-27632, muscle contraction is decreased. Rho-kinase is often shown in high amounts in hypertension, or high blood pressure, which has long been considered a factor for ED because of its affect on the vascular system. Also, sexual impotence is a potential side effect of several classes of blood pressure medications and a primary reason for men to quit these medications. An agent that has a selective relaxant activity on the vascular beds with high basal tone that is devoid of adverse effects on sexual function would be an ideal candidate for the treatment of ED in this population.

For the study, researchers used 13 rats genetically engineered to have high blood pressure (60 percent to 70 percent higher than normal) and compared them to the normotensive control group. They recorded mean arterial pressure and mean cavernosal pressure in both basal resting state and following penile nerve stimulation. Both groups received injections of Y-27632 into the penile smooth muscle. Researchers found significant improvement in the erectile response in the hypertensive group.

After intracavernosal injection of Y-27632, the hypertensive rats showed an increase of 25 percent to 110 percent in peak mean cavernosal pressure. The drug did not affect blood pressure in the normotensive control group.

According to Mahadevan Rajasekaran, Ph.D., senior author, the study is important because it shows a new pathway for treating ED due to vascular causes. Current oral treatments for ED, such as sildenafil citrate, target the nitric oxide pathway and sustain relaxation of the penile smooth muscles, rather than decrease contraction.

"This medication has shown that it will be effective even when the nitric oxide pathway is blocked," he said. "That gives us an advantage in treating erectile dysfunction."

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TOPICAL SOLUTION IMPROVES SEXUAL RESPONSE IN WOMEN

ORLANDO - May 25, 2002 - Women with female sexual arousal disorder (FSAD) showed increased subjective and objective sexual responses after using topical alprostadil solution - which dilates local blood vessels where applied - according to a new study conducted by Marc Gittelman, M.D., medical director of South Florida Medical Research and clinical director of his practice Uro-medix in Miami, FL. He will present the findings at the American Urological Association Annual Scientific Meeting during a poster session on May 27 from 10 a.m. to 12 p.m.

FSAD is a subtype of female sexual dysfunction (FSD), common in women who are postmenopausal. The other subtypes include decreased sexual desire disorder, orgasmic disorder and sexual pain disorders.

Seventy-eight women, ages 40 to 70, with FSAD and stable hormonal replacement participated. Half of the group received placebo and the other half received topical alprostadil to apply to the clitoris and surrounding tissues. Patients recorded their sexual responses - genital lubrication, pelvic fullness, pelvic warmth/tingling, level of sexual arousal and level of sexual satisfaction - to explicit videos.

All women who received alprostadil had increased localized blood flow to the vulva and increased genital lubrication - both signs of positive sexual response. There were no reports of significant side effects.

"Female sexual dysfunction is very common, occurring in 20 to 50 percent of the general population, while one survey indicates that 20 percent of adult women have female sexual arousal disorder," said Gittelman. "To date, there are no FDA approved pharmacological treatments for this disorder, but topical alprostadil may be an appropriate on-demand treatment for women suffering from female sexual arousal disorder."

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TECHNOLOGY ALLOWS DOCTORS TO MAKE ROUNDS FROM THE COMFORT OF THEIR HOMES

ORLANDO - May 25, 2002 - Just as teleconferencing allows us to share information and ideas, a new technology called urologic telerounding can provide sufficient clinical information for physicians to manage the inpatient process while not physically present at the hospital, according to a new study conducted by Fernando J. Kim, M.D., urologist in practice at The Johns Hopkins Medical Institution in Baltimore, MD. His findings will be presented at the American Urological Association annual meeting on May 25, 2002.

With telerounding, physicians in a remote location can perform clinical rounds with the assistance of on-site clinicians by using real-time interactive audio-visual technology to gather sufficient clinical information to allow remote management.

Using commercially available equipment - a laptop computer, digital camera, microphone and wireless network system - a mobile computer cart is wheeled room to room by residents and attending physicians. Audio and video signals reach the remote-attending physician via Internet T3 and cable connections.

This process allows clinicians to obtain objective clinical data online, and evaluate and participate in the inpatient management process even when he/she is not physically present at the hospital. Other recently explored medical applications include teleconsulting (which allows specialists to consult each other about clinical aspects of a case) and telesurgery (a technique that permits the telementoring of another surgeon during the procedure from a different location).

To test its efficacy, three physicians created 10 telerounding simulations and evaluated them by the remote physician's ability to make diagnoses and manage decisions appropriate to the clinical presentation. Mean connection time was between 2.3 and 3.5 minutes.

RealTime Audio and visual quality allowed visualization of specific details on physical exams. Physicians effectively acquired adequate clinical information, including vital signs and performance results from a questionnaire/physical exam with the assistance of an on-site physician.

"Data collection was a success in acquiring results sufficient for the remote urologists to make appropriate decisions," Kim said. "Although further studies are needed to assess validity and patient satisfaction with this mode of health care delivery, the study shows that telerounding could revolutionize the way we practice medicine today."

Kim will serve as chief of Urology at Denver Health Medical Center in Colorado this summer and plans to continue this line of research. Concurrently, The Johns Hopkins Medical Institution will perform clinical studies to determine patients' comfort level with these procedures.

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TESTOSTERONE DEFICIENCY LINKED TO SEXUAL DYSFUNCTION IN YOUNG WOMEN

ORLANDO - May 25, 2002 - Young women with normal menstrual cycles can be susceptible to female sexual dysfunction (FSD) as a result of low testosterone levels, according to a new study by researchers from the Lahey Clinic and Boston University in Massachusetts. The research is being presented at the 97th Annual Scientific Meeting of the American Urological Association in Orlando. Ricardo Munarriz, M.D., will present the study during a moderated poster session on May 26, 2002.

Pre-menstrual women - with normal menstrual cycles and not taking oral contraceptives - were given questionnaires and interviews to determine whether they suffered from sexual dysfunction. The study involved 36 women - split evenly between the test group and the control. Researchers then monitored testosterone levels and adrenal androgen precursor hormones in both groups of women, and stimulated the adrenal gland with adrenocorticotropic hormone (ACTH) - the pituitary hormone that regulates the adrenal.

Numerous studies have linked low levels of testosterone to FSD. Unlike men, who generate testosterone only from the testicles, women generate the hormone from two glands: the ovary and the adrenal. Because the women in the study had normal menstrual cycles, researchers focused on the adrenal gland, which makes five hormones in the body, including testosterone, out of cholesterol. Because the women with FSD had low levels of Dehydroepiandosterone (DHEA, a n adrenal hormone), researchers explored the possibility of an adrenal defect.

Hormone levels were monitored in both groups over a period of one hour before and after ACTH stimulation. Results showed that the baseline levels of all five hormones generated from the adrenal gland were low in patients with FSD. However, both the normal controls and the patients showed stimulation by ACTH, suggesting that an enzyme defect could be responsible for the condition.

"These enzymes are not turned on," said Andre Guay, the Lahey endocrinologist who is lead author of the study. "But they have the potential to be turned on."

"This is totally controversial," Guay said. "But we at least showed that young, normal women can suffer from sexual dysfunction due to testosterone deficiency."

"We've found a group of women that isn't supposed to exist."

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UNIVERSITY OF MARYLAND UROLOGISTS GIVE HOPE TO MEN WHO INITIALLY FAIL TO RESPOND TO SILDENAFIL CITRATE

The University of Maryland urologists will describe the results of their study today (May 25) at the American Urological Association's scientific meeting in Orlando, Florida.

--More--

Michael J. Szostak, M.D. a urology resident at the University of Maryland Medical Center, assisted Dr. Sklar in the study, which was not funded by any pharmaceutical company.

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VACCINE REDUCES RECURRENT URINARY TRACT INFECTIONS IN ADULT WOMEN

ORLANDO - May 25, 2002 - Vaginal mucosal vaccine increased women's resistance to recurrent urinary tract infections (RUTIs), according to a new study conducted by Walter Hopkins, Ph.D. from the University of Wisconson in Madison. The study findings, also demonstrating safe deliverance of a vaccine in vaginal suppository form, will be presented at the American Urological Association annual meeting on May 25 during a poster session starting at 1:00 p.m.

This phase two clinical trial involved 54 women with RUTIs - that is, at least three UTIs in the past year (an average of seven). The women were taken off current preventive antibiotics and given a vaginal suppository of vaginal mucosal vaccine - containing heat-killed urinary tract bacteria - to immunize against future infections.

Subjects were randomly assigned into one of three groups, for six total treatments per subject over a 4 1/2 month period: placebo only, primary immunization (half vaccine/half placebo doses) and primary immunization plus boosters (all vaccine doses). All women were followed for five months to record adverse effects and RUTIs.

At the study's end, women receiving all vaccine doses remained free of infections for a longer period of time than the other groups. Of those receiving all vaccine doses, 55 percent had no infection, whereas 89 percent of placebo-treated group developed UTIs. There were no reports of significant adverse effects. If the treatment is FDA approved, it will be the first human vaccine delivered in vaginal suppository form.

"With the increasing number of drug-resistant bacteria, it is important to develop preventive antibiotic alternatives like this," said Hopkins. "Recurrent urinary tract infections remain a significant problem. This study shows promise and we're planning to institute a third phase of trials in multiple centers."

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DISCHARGES DELCINE FOR UROLOGIC MALIGNANCIES, BUT COSTS DO NOT FOLLOW SUIT

Study based on Health Care Utilization Project Data

ORLANDO - May 25, 2002 - A study of discharge data from 1993 to 1997 reveal that lengths of stay decreased significantly for prostate, bladder, and kidney cancers while it did not change for testis cancer. In addition, the total number of discharges decreased for all but kidney cancer, according to a study by Dr. Badrinath R. Konety, assistant professor in the department of urology at the University of Iowa. He will present the findings at the American Urological Association annual conference May YY.

Testis cancer had the steepest decline in number of discharges (50 percent), indicating that more patients are being treated on an outpatient basis. In-hospital mortality decreased for all diseases with prostate cancer mortality decreasing the most (51 percent). The use of non-hospital institutional care and home health care increased for kidney cancer (49 percent and 28 percent) and bladder (27 percent and 11 percent), while declining for prostate cancer (1 percent and 16 percent).

Meanwhile, the decreases in lengths of stay did not consistently correspond to a decline in inflation adjusted mean hospital charges. Charges for hospital admissions associated with bladder cancer increased significantly between 1993 and 1997(28 percent), while charges per hospital admission decreased significantly for prostate and kidney cancers. There was no change with respect to testes cancer.

"The study is encouraging in that we know for sure patients are spending less time in the hospital and this is translating into a reduction in charges for prostate and kidney cancers," Dr. Konety said. "However, more efforts are required to improve cost-effective care delivery for bladder cancer patients. One reason costs may not be decreasing correspondingly is that we have more sophisticated, and therefore more expensive treatments available.."

The data used in the study was taken from the National Inpatient Database (NIS) of the Health Care Utilization Project (HCUP), a collaborative research effort of federal state and industry organizations. The NIS is a 20 percent sample of discharge data collected from a random sample of hospitals in different states and contains seven million records.

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VACUUM-INDUCED CLITORAL ENGORGEMENT DEVICE SUCCESSFULLY TREATS FEMALE SEXUAL DYSFUNCTION IN DIABETICS

ORLANDO - May 25, 2002 - A device that uses vacuum pressure to increase blood flow to the clitoris and vagina was successful in addressing arousal aspects of female sexual dysfunction (FSD), according to a new study conducted by Kevin L. Billups, M.D., urologist in practice at the EpiCenter for Sexual Health & Medicine in St. Paul, MN. His findings will be presented at the American Urological Association Annual Scientific Meeting on May 28 during a poster session beginning at 1 p.m.

The test group consisted of 13 diabetic women. This condition typically causes sexual dysfunction in both men and women due to decreased blood flow. Use of the EROS Therapy™, produced by UroMetrics Inc, in St. Paul, MN, both immediately prior to intercourse and at intervals not followed by intercourse, led to greater sensation and increased sexual satisfaction in 85 percent of the patients both one month and three months following treatment.

In addition, after three months of treatment, 92 percent of the patients reported increased genital lubrication and 62 percent reported an increased ability to achieve orgasm. No side effects of the EROS device were noted.

Women were instructed to use the device at least four times per week and at least two times per week prior to attempting intercourse. All women had normal testosterone and estradiol levels. The Female Intervention Efficacy Index (FIEI), a validated questionnaire that subjectively measures changes in sensation, lubrication, orgasm and sexual satisfaction, was used to assess outcome efficacy after one and three months of the therapy.

"We are now beginning to address female sexual dysfunction from the perspective that some aspects of FSD are likely caused in part by decreased blood flow to the clitoris or vagina. Poor genital blood flow is believed to contribute to female arousal or orgasm disorders similar to the role of vascular disease in male erectile dysfunction," Billups said. "This current study also has implications for non-diabetic women with sexual dysfunction as well."

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ZOLEDRONIC ACID REDUCES BONE FRACTURE RISKS IN PROSTATE CANCER PATIENTS

ORLANDO - May 25, 2002 - Zoledronic acid provides significant clinical benefits to patients with hormone-refractory prostate cancer (HRPC), according to a new study conducted by Fred Saad, M.D., urologic oncologist in practice at Hôpital Notre-Dame of the University of Montreal. His findings will be presented at the American Urological Association annual meeting during a podium session on May 27 at 2:20 p.m.

Advanced prostate cancer often leads to metastatic bone disease, in which cancerous cells spread to the bone to weaken, cause pain and increase fracture risk - which is a skeletal-related event (SRE). SREs also include spinal cord compression, the need for radiation or surgery to control bone pain, or a change in chemotherapy treatment due to bone pain.

Prostate cancer bone metastases are predominantly osteoblastic (cells that form new, painful and easily fractured bone), which is different from most other cancers.

The multi-center trial included 643 patients. All had HRPC - prostate cancer that progressed after hormonal therapy - and one-third had a previous SRE. Median age was 72 years, median time between prostate cancer diagnosis and study entry was five years, and median time between the first bone metastasis (most often detected by a nuclear bone scan) to treatment was two years.

Every three weeks for 15 months, patients received placebo or four milligrams zoledronic acid via 15-minute infusion. It is a third-generation bisphosphonate; a drug that stops cells called osteoclasts from eating away bone. This drug appears to also render the bone more resistant to the effects of cancer cells invading the bone.

The effects of zoledronic acid were consistent across all SREs. Treated patients had 25 percent fewer SREs than those who received placebo, and the time of their initial SRE was significantly delayed.

Zoledronic acid also delayed time to the first pathologic fracture and total number of SREs: 33 percent versus 44 percent of placebo-treated patients. It reduced long-bone fractures and vertebral fractures (10 and four percent versus 16 and eight percent for placebo-treated patients, respectively).

The treatment was safe and well tolerated with a safety profile similar to other intravenous bisphosphonates. Zoledronic acid appears to be the most effective bisphosphonate for HRPC.

"Zoledronic acid is the first drug to demonstrate effectiveness in metastatic prostate cancer patients, meaningfully reducing skeletal-related events" Saad noted. "Our next step is to see whether it can prevent bone metastases from appearing. Since this group of patients were extremely advanced in their disease we hope that with earlier use of zoledronic acid the effects will be even more impressive."

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HORMONE THERAPY WITH INNOVATIVE DELIVERY SYSTEM AVAILABLE FOR PROSTATE CANCER

NEW YORK - May 28, 2002 - Today Sanofi-Synthelabo Inc. announced the commercial availability of ELIGARD(tm) 7.5 mg (leuprolide acetate for injectable suspension), an innovative hormone therapy for the palliative treatment of advanced prostate cancer. ELIGARD 7.5 mg suppresses testosterone to traditional castrate levels and also meets the more stringent guidelines of the National Comprehensive Cancer Network (NCCN). The recently approved one-month formulation employs a unique drug delivery system that delivers leuprolide acetate subcutaneously. The announcement came at the conclusion of the Annual Meeting of the American Urological Association in Orlando.

An open-label, multicenter study evaluated 120 patients with advanced prostate cancer who were treated with six monthly injections of ELIGARD(tm) 7.5 mg. Eighty-nine patients had stage C disease and 31 patients had stage D disease. This study evaluated the achievement and maintenance of serum testosterone suppression over six months of therapy. Serum testosterone was suppressed to below =50 ng/dL by Day 28 (Week 4) in 112 of 119 (94.1 percent) patients remaining in the study. The remaining seven patients all attained serum testosterone suppression by Day 42. At the conclusion of this trial (month six) all 117 patients who completed the study had testosterone levels at or below 50 ng/dL.

In addition to controlling testosterone levels, another consideration when treating men with hormone therapy is the side effects. In the patient populations studied, a total of 86 hot flash/sweats adverse events were reported in 70 patients, of these, 71 events (83 percent) were mild; 14 (16 percent) were moderate; one (one percent) was severe.

ELIGARD 7.5 mg uses the ATRIGEL(r) drug delivery system to provide continuous release of leuprolide acetate over a one-month treatment period. The ATRIGEL drug delivery system consists of biodegradable polymers. The ATRIGEL system is mixed with the active drug and then injected just under the skin as a viscous liquid. The liquid quickly solidifies into a solid implant, essentially a small bead of medication that slowly dissolves to release a continuous supply of leuprolide acetate for the one-month period.

"Many advances have been made in the hormonal treatment of prostate cancer," said A. Oliver Sartor, M.D., director of the Stanley S. Scott Cancer Center at LSU Medical School in New Orleans, La. "In particular, ELIGARD 7.5 mg utilizes a new delivery system for a proven drug that has been used in prostate cancer for more than a decade. This delivery system has proven to deliver a leuprolide acetate over a 30-day period in a manner that results in a consistently very low level of testosterone thereby helping to optimally manage this difficult disease."

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