New clues in prostate cancer therapy-(USA TODAY-28/07/2005)

Two new studies could help men and their doctors better treat prostate cancer. Doctors have struggled for years over how aggressively to treat prostate cancer, a disease more common than it is fatal, says Stephen Freedland, an author of one of the articles and a clinical instructor at Johns Hopkins School of Medicine in Baltimore. A man has a 17% lifetime risk of being diagnosed with prostate cancer, for example, but a 3% risk of dying from it. Yet about one in three prostate cancer patients who have surgery eventually show signs of a relapse, according to a study published today in the Journal of the American Medical Association. Doctors have few reliable ways, however, to determine which of these relapses, detected by PSA tests, will be deadly and which will prove relatively harmless. The article suggests that doctors might be able to combine three measurements to select those who need strong therapy.

•Time to recurrence: the time it takes after surgery to detect levels of PSA, or prostate-specific antigen, in the blood. This protein, which is made by the prostate, should be undetectable after surgery if a patient is cancer-free. The presence of PSA in the blood after surgery indicates that some tumor cells remain hidden in the body.

•PSA doubling time: the time it takes for the PSA level to double after surgery. This measures how quickly the cancer is growing.

•The Gleason score: a measure of aggressiveness assigned after examining prostate cancer cells under a microscope. Scores above 8 are considered the most dangerous.

In the study, men whose PSA doubled in less than three months survived an average of six years. Among these men, however, those whose cancer recurred in less than three years and who had Gleason scores of 8 to 10 survived about three years. After 15 years, no prostate-cancer-related deaths were found in men whose disease took more than three years to return and whose PSA took more than 15 months to double. Men who are at high risk could benefit from aggressive treatments, such as hormone suppression and chemotherapy, Freedland says.

A study in the same journal reported another potential way to predict which prostate cancers are most worrisome.

Among patients treated with radiation, men had the greatest risk of death if their PSA increased by more than 2 nanograms per milliliter in the year before they were diagnosed. Some experts say that doctors need to verify these results before changing the way they treat patients. Mitchell Anscher, a professor at Duke University who wrote an editorial accompanying the articles, notes that hormone suppression and chemotherapy cause serious side effects. Chemo can make patients very sick. Suppressing testosterone, sometimes called "chemical castration," can cause impotence, hot flashes and bone loss. "You don't yet know if those treatments are really going to do (patients) any good," Anscher says.

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Prostate Cancer Radiation: Study Shows Many Men Can Still Have Erections, Avoid Incontinence-(Yahoo News-22/07/2005)

New research shows that most men who get radiation therapy for early stage prostate cancer can still get an erection and are not incontinent a year later. The finding appears in the International Journal of Radiation Oncology, Biology, and Physics. The researchers included Steven Feigenberg, MD, of the radiation oncology department at Philadelphia's Fox Chase Cancer Center.

Prostate cancer is the No. 2 cause of cancer deaths and the most common cancer (except skin cancer) among U.S. men, according to the American Cancer Society (ACS). The odds of getting or dying from prostate cancer rise with age. More than three out of four new cases are found in men older than 65. Men in that age range also account for 90% of prostate cancer deaths. Prostate cancers often grow slowly. But, like many cancers (and other diseases), the sooner it's flagged, the better. Treatment may include radiation, surgery, or "watchful waiting." Because prostate cancers may advance so slowly, men with early prostate cancer can opt for watchful waiting. These localized cancers are unlikely to cause men -- especially older men -- any problems during their lifetimes, according to the National Cancer Institute.

Surgery to remove the prostate can result in various complications including urinary incontinence and erectile dysfunction. The risk of impotence can be reduced by nerve-sparing surgery. Radiation treatment can involve external beam treatment or radiation emitted from radioactive "seeds" implanted in the prostate (prostate brachytherapy). Both of these treatments kill cancer and healthy cells. Urinary problems and erectile dysfunction are also side effects of this treatment.

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Early PSA screening may reduce risk of prostate cancer death: study-(Yahoo News-08/07/2005)

Early screening for prostate cancer in men without symptoms could significantly reduce their risk of going on to develop an advanced and usually deadly form of the disease, a Canadian study suggests. Researchers at the universities of Toronto and British Columbia found that early PSA testing may reduce the risk of metastatic prostate cancer - the kind that spreads beyond the walnut-sized gland - by more than a third.

The study compared the PSA testing histories of 236 men with advanced prostate cancer against those of a control group of men without metastatic cancer - 462 who either didn't have the disease at all or had a localized tumour. "What we found was, in fact, that the risk of metastatic prostate cancer was about 35 per cent less in the men who had been screened," said study co-author Dr. Vivek Goel, a professor of health policy management and evaluation at the University of Toronto.

The screening tool is a simple blood test that detects levels of what's known as prostate specific antigen, or PSA. While small amounts in the blood are normal, higher levels could indicate cancer. Yet the test remains controversial because it is not foolproof and may cause undue distress. High PSA levels can exist when no cancer is present or a tumour may be a type that doesn't spread to other parts of the body, so men can live normal lives for many years to come. But PSA testing may also flag the type of prostate cancer that will go on to spread if left untreated, said the researchers.

"Our study . . . adds to the body of evidence that shows that it does have potential for having a fairly significant effect in reducing the risk of advanced prostate cancer and, by extrapolation, the death from prostate cancer," Goel said. That's because detecting prostate cancer before it has spread allows for early and effective treatment. The study adds weight to the argument that PSA testing should be routine for men - as mammography and pap smears are for women - not just when a doctor suspects cancer because of symptoms, he said. "There may be greater benefit from an organized screening program." But the test, when used strictly as a screening tool, is covered by only about half of Canada's provincial health plans.

An estimated 20,500 Canadian men will be diagnosed with prostate cancer this year, and about 4,300 will die. Prostate cancer is the second-highest cause of cancer death among North American men after lung cancer. "Our study shows a fairly significant benefit for early screening using the prostate specific antigen test, so these results are important for men and their doctors," said Dr. Jacek Kopec, professor of health care and epidemiology at the University of British Columbia and lead author of the paper.

The head of the Canadian Cancer Society, which helped fund the study, called the findings welcome news for Canadian men. "The results of this study are interesting and add to the body of evidence about the PSA test," said Dr. Barbara Whylie. "We look forward to the results of two other large, ongoing trials to validate these findings. In the meantime, we will continue to encourage men to discuss this test with their doctors until more definitive answers about the benefits of the PSA test are available."

The study, published in the August issue of the Journal of Urology, recruited men from the Greater Toronto Area in 1999-2002. They ranged in age from 45 to 84; the average age of prostate cancer diagnosis was 68. Researchers obtained self-reported information about their lifestyles, health history and use of health services. They also received permission to review medical records and history of PSA screening.

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Prostate cancer screen test flawed, experts say-(Reuters-05/07/2005)

A screening test for prostate cancer taken by millions of men every year is not terribly accurate and not even the best result ensures that a man is cancer-free, experts said. They found the standard prostate-specific antigen, or PSA test, produces many false positives and false negatives -- meaning some men who think they do not have cancer actually do, while others may undergo uncomfortable biopsies only to learn there is no tumor after all. "Patients have assumed, 'My PSA is below 4. It's normal. I have no risk'," Dr. Ian Thompson of the University of Texas Health Science Center at San Antonio, who led the study, told a news conference.

In fact, some men with PSA levels of 1 had prostate cancer, his study showed. Others with higher PSA levels did not have prostate cancer. If all men got biopsies when PSA reached 1.1, more than 80 percent of all prostate cancers would be detected, Thompson said. But 61 percent of men who got biopsies would turn out not to have cancer. A cutoff of 2.6 would detect only 40.5 percent of cancer cases. This could explain why some men die of prostate cancer despite intensive screening programs, the researchers said. "This is going to require a re-education not just of patients but of physicians," Thompson said. "What should men do? Our take home message ... they should consider the risk factors."

Men whose fathers or brothers had prostate cancer, black men and others have a higher risk than the general population, for instance, he said. "PSA, like blood pressure, like cholesterol, like many other tests, shouldn't be considered to be 'normal' or 'abnormal' but should be considered as showing a range of risk," Thompson said.

For their study, published in the Journal of the American Medical Association Thompson and colleagues examined more than 5,000 men who took part in a larger study that showed the drug finasteride, sold by Merck and Co. under the brand name Proscar, could help prevent prostate cancer in some men. All the men in the latest study got a placebo instead of finasteride and they were watched for seven years. At the end, all of them got biopsies, regardless of PSA level. Nearly 22 percent of the 5,000 men were found to have prostate cancer, either during the seven years or at the end. The good news was that PSA was accurate in detecting high-grade prostate cancers -- those more likely to spread a kill a patient.

Prostate cancer affects more than 200,000 men a year in the United States and will kill 29,000 in 2005, according to the American Cancer Society. It is usually a slow-growing cancer and older patients often can simply keep an eye on it because they are likely to die of something else first. But there is no good way to tell who can safely get away with "watchful waiting."

An American man has a 17 percent lifetime risk of prostate cancer, but only a 3 percent risk of dying from it. In 2001 about 75 percent of U.S. men 50 and older reported having at least one PSA, and 54 percent say they have it measured regularly.

In a separate study, researchers at the American Cancer Society found that men who use aspirin and other nonsteroidal anti-inflammatory drugs or NSAIDs have a slightly reduced risk of prostate cancer. But the society said their findings from a study of 70,000 men do not yet justify taking analgesics primarily to prevent prostate cancer.

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Effects of diet on prostate cancer-(Yahoo News-29/01/2005)

Studies show men in Japan and China have as much as 90 percent less prostate cancer than American men. With the large number of immigrants in Hawaii from Japan, researchers at the University of Hawaii set out to determine why this difference exists. Their research involved Japanese-Americans including first generation immigrants and their offspring. This was known as the migrant study.What they found was that cancer rates varied between Japan and Hawaii and that cancer rates varied between generations within Hawaii.

Radiation Seeds May Be Enough for Prostate Cancer-(Reuters Health-26/01/2005)

A new study suggests a man's weight may affect the accuracy of a common test to detect prostate cancer, leading researchers to warn that doctors could be missing the dangerous cancer in obese men. Researchers at the University of Texas Health Science Center in San Antonio studied 2,779 men without prostate cancer between 2001-04. In the study released online in the journal Cancer, they reported finding that the more obese the men were, the lower their levels of prostate-specific antigen or PSA. A PSA of 4.0 or lower usually means no cancer.

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New Clue to Prostate Cancer May Improve Treatment- (HealthDayNews- 16/11/2004)

New information about the activity of a hormone-sensitive cell receptor could improve the treatment of prostate cancer, according to a study in the November issue of Cancer Cell. Androgen receptors (AR) play a key role in prostate cancer progression and are a prime target for treatment of the disease. Now, researchers at the David Geffen School of Medicine at UCLA have discovered that AR activity is not triggered by molecules called EGFR -- as was previously believed -- but by another chemical pathway, called HER2/ERBB3.

The finding may explain the limited success of the EGFR-inhibiting drug Gefitinib, which was recently tested against prostate cancer in clinical trials. About a third of prostate cancer patients develop metastatic disease and receive treatment to stop androgen production and AR activity. However, this treatment eventually becomes ineffective. The UCLA researchers suggest that drugs that target HER2, instead of EGFR, may prove more effective in treating these types of prostate cancers.

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Quality of life after prostate cancer diagnosis-(Yahoo News-12/10/2004)

A study compares quality of life among men treated with either surgery or radiotherapy for prostate cancer. Previous research has suggested that radical prostatectomy reduces disease-specific mortality among men with prostate cancer, compared to 'watchful waiting'. But surgery has a negative impact on sexual and urinary functioning, and does not improve overall mortality rates. Radiotherapy is another treatment option and men with prostate cancer, and their doctors, need information comparing the outcome and impact of the different treatment plans to make decisions. Researchers at the National Cancer Institute in the US now report on a comparison of over 1,000 men having either radical prostatectomy or radiotherapy.

Five years after diagnosis overall sexual functioning had declined in both groups. Two years after diagnosis, however, 82 per cent of those who had had surgery experienced impotence, compared with 50 per cent of those having radiotherapy. More patients in the surgery group experienced urinary problems - 15 per cent - compared to the radiotherapy group - four per cent. But more men who had radiotherapy had bowel problems than those in the surgery group. The findings should help guide doctors and their patients in treatment decisions about prostate cancer.

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Research and Markets: Prostate Cancer: New Guidelines and R&D Advancement; An Analysis of Prostate Cancer Therapeutics: Progress, Developments and Forecasts-(BUSINESS WIRE-14/09/2004)

Research and Markets has announced the addition of Prostate Cancer: New Guidelines and R&D Advancement to their offering. In this issue of Cancer Highlights, the field of prostate cancer therapeutics is analyzed. The progress in this field is evaluated and industry related activities are described. Treating prostate cancer is a complicated task. This fact increases the possibilities to find business opportunities, which has already been realized by many who have turned the field of prostate cancer therapeutics into a highly competitive area. Improved methods for diagnosing prostate cancer will enhance the market size and make this area even more interesting in the future.

The year 2004 has been a year of change in terms of treating patients with prostate cancer. New guidelines for the use of androgen suppression and possible benefits from combinations with radiation therapy are described in this report. Subset analysis has demonstrated a survival benefit from radiotherapy only for patients with a biopsy Gleason score higher than 6 after short-term neoadjuvant hormonal therapy. In the April issue of Urology, GlaxoSmithKline published results indicating that long-term treatment with Avodart (dutasteride) resulted in a low incidence of drug-related side effects. The incidence decreased with duration of treatment. Other major drugs that will be of interest in relation to these findings are Zoladex, Proscar and Casodex. These are all included in this progression analysis.

The antiandrogens are becoming an increasingly realistic alternative for future prostate cancer prevention. Strategies and projects related to cancer prevention and especially prostate cancer prevention have been studied. A second major topic is the combination of Aventis' Taxotere in combination with prednisone. This issue presents the latest data on utilizing a combinatory therapeutic strategy of docetaxel and different investigational drugs such as Avastin, Herceptin, GTI-2501, ILX-651, calcitrol, Genasense, Gleevec, SGN-15, Thalomid and Velcade.

In June 2004, the American Society of Clinical Oncology (ASCO) released new guidelines for treating men with androgen-sensitive prostate cancer. Taxotere injection concentrate in combination with prednisone is moving forth as a treatment for advanced prostate cancer that is no longer responding to hormonal therapy. The ASCO expert panel on androgen deprivation therapy (ADT) has reached the conclusion that the use of nonsteroidal anti-androgens can be viewed as an alternative to orchiectomy or drug treatment with luteinizing hormone releasing hormone agonists (medical castration). Since no studies have satisfactory demonstrated a survival advantage for starting treatment earlier, the panel feels that no specific recommendations can be issued regarding the question of early vs. deferred ADT.

Researchers involved in the Early Prostate Cancer Program have concluded that hormone therapy initiated immediately following initial therapy reduces the risk of cancer progression. For men with localized or locally advanced prostate cancer treated with initial radiation therapy, immediate hormone therapy also improves progression-free survival.

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PSA test saves lives and should not be abandoned, urges Canada's prostate cancer experts-(Yahoo News-13/09/2004)

The Prostate Cancer Research Foundation of Canada, the leading national organization devoted solely to eliminating prostate cancer, warns that a study published in the October issue of the Journal of Urology may discourage men from taking advantage of the most important early warning device for prostate cancer -- the PSA (or prostate specific antigen) test. "The PSA test is the most valuable tool we have for early detection of prostate cancer," said John Blanchard, President and CEO of the Prostate Cancer Research Foundation of Canada, and a recent prostate cancer survivor. "The PSA test is not perfect. Nor is it designed to say whether a man has prostate cancer or not. The majority of prostate cancer specialists rely on the PSA test for early detection and the 95% cure rates that early detection offers," says Blanchard.

"The PSA test is a very accurate indicator of cancerous growth in the prostate," said Dr. Laurence Klotz, Chief of Urology, Sunnybrook and Women's College Health Sciences Centre in Toronto, and Chair of the Foundation's Scientific and Medical Advisory Committee. "The PSA test provides physicians with an early indication of the cancer, and leads to other tests for the disease, including ultrasounds, biopsies and the Gleason score which evaluates how aggressive the cancer is. With this diagnostic tool, we can catch the cancer earlier and increase our number of treatment options."

Prostate cancer afflicts one in eight Canadian men and their families. About 19,000 Canadian men will be diagnosed with prostate cancer this year, not including the cases that develop but go undiagnosed. Over 4,500 Canadian men will die from prostate cancer this year.

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Prostate cancer test under fire. A pioneer of the procedure says is leading to thousands of needless surgeries-(Yahoo News-13/09/2004)

A pioneer of the PSA prostate cancer test taken by millions of men each year now says the test has virtually no bearing on how much cancer is present. What's more, adds Dr. Thomas Stamey of Stanford University, the test is leading to thousands of needless surgeries to remove tiny cancers that may never have become life-threatening. The PSA, or prostate specific antigen test, measures a protein produced by the prostate gland. It has been thought that the higher the blood PSA level, the more likely there is prostate cancer. Prostates are frequently removed in response to higher than normal blood PSA levels.

However, a study published in the October issue of the Journal of Urology concludes elevated PSA levels are almost always signs of a harmless increase in the size of the prostate. Stamey and colleagues from Stanford's department of urology examined tissue samples from more than 1,300 prostates removed by doctors at Stanford during the last 20 years. They looked at the size and grade of each tumour, then compared the cancers with the PSA test taken before the prostate was removed. "In the last five years, only two per cent of the prostate cancer removed at Stanford had any relationship to PSA," says Stamey, a professor of urology.

He published the original research in 1987 in the New England Journal of Medicine showing increased blood PSA could be used to detect cancer in the prostate gland. Today, with PSA screening so widespread, many cancers are being caught earlier. However, says Stamey, while the test frequently finds cancer today, it doesn't necessarily mean the need for surgery, radiation, hormonal or other aggressive treatments that can leave a man impotent and incontinent.

"Every man needs to recognize that prostate cancer is ubiquitous," Stamey said in an interview. About eight per cent of men in their 20s have prostate cancer, and the proportion rises steadily with each decade of life, until 70 per cent of men have prostate cancer in their 70s. Although we all get it if we live long enough, it's important to recognize that the death rate is very small: 226 men per 100,000 over 65 years of age." The death rate from lung cancer, in contrast, is 30,000 per 100,000 men. His team is searching for a better blood marker for prostate cancer. In the meantime, Stamey recommends a yearly digital rectal exam for all men over 50. 

Some Canadian cancer specialists caution against abandoning the PSA test just yet. "A more logical approach is to suggest we continue with current PSA testing until a better marker" for the disease is found, says Dr. Chris Morash, a urologic oncologist at The Ottawa Hospital.

An estimated 20,100 Canadians will be diagnosed with prostate cancer this year; another 4,300 will die of the disease.

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Research reveals potential new target for prostate cancer drugs UC-(Yahoo News-26/08/2004)

Scientists have determined the precise molecular structure of a potential new target for treating prostate cancer, a disease driven in part by abnormal testosterone activity. The target is part of the androgen receptor, a protein essential for testosterone to function in human cells. Prostate cancer is the most common cancer among men. The androgen receptor and testosterone -- technically, 5-alpha dihydrotestosterone -- each drive prostate cancer at different stages of the disease. A common prostate cancer treatment uses drugs that compete with testosterone, blocking its ability to bind with the androgen receptor and so reducing the hormone's effect. But cancer tends to become resistant to these drugs. The new research provides a novel strategy to block activation of both the androgen receptor and testosterone.

UCSF scientists determined the atom-by-atom topography of the pocket where proteins known as coactivators bind to the human androgen receptor to enable testosterone to trigger gene activity. Knowing the detailed shape greatly boosts the likelihood of developing a drug to block this binding and turn off androgen receptor activity, the scientists report. The research is being published online August 24 by Public Library of Science (PLoS) Biology. 

"Drugs that block testosterone binding are not effective in the long term against prostate cancer," says Robert Fletterick, PhD, UCSF professor of biochemistry and biophysics and senior author on the PloS Biology paper. "The shape of the site we have determined -- where coactivators bind to the androgen receptor -- specifies the design for a new class of drugs. Simple versions of the 'ultimate' drug will be tested in cancer cells this year." With an aggressive search for the right chemicals, candidate drugs might be tested in human patients within three years, he says. UCSF has filed for a patent revealing the nature of the coactivator site on the androgen receptor.

The male hormone testosterone controls development and maintenance of the male reproductive system and other tissues such as bone and muscle. The hormone is present in smaller amounts in females, where it also helps form muscle and bones. The scientists determined the shape of the binding pocket on the androgen receptor -- technically, the coactivator binding interface -- by exposing it to billions of randomly chosen protein fragments, or peptides, and selecting for those that bind best. They then imaged the peptides that bind best using a technology called X-ray diffraction that shows every atom of the peptide and the receptor, and how they interact.

The researchers are now testing the ability of different small molecules to bind to the androgen receptor binding site. They hope to demonstrate the potential of developing a drug that will bind more strongly than the normal coactivator, thereby shutting down androgen receptor activity. Knowing the molecular shape of the target speeds development of a new drug about ten-fold, Fletterick says, and helps assure that the drug will work as expected. The new structural information from the limited number of peptides and small molecules that bind well to the coactivator sites can be used by chemists to screen from among thousands of "best-fitting" molecules to find those with the precise configuration and traits needed for a good drug to block coactivator binding, Fletterick says. In addition, chemists can use the information to synthesize new molecules with the required drug traits.

It remains uncertain whether researchers can identify a small molecule drug candidate that binds to the androgen receptor more strongly than the coactivators themselves do, Fletterick cautions. Cancer researchers do not know which coactivators bind with the androgen receptor when cancer strikes, Fletterick adds. But the research may lead to selective drugs that permit "good" activators to bind while blocking those that promote cancer progression. This possibility is the focus of new research by several UCSF labs. The highly detailed structure of the coactivator binding site revealed by the research explains the unusual behavior of this hormone's receptor, says Eugene Hur, BS, UCSF graduate student in biophysics and lead author of the scientific paper. Most hormone receptors bind to coactivator sequences rich in the amino acid leucine, but the androgen receptor is unique in preferring bigger, bulkier bonding partners. The explanation appears to lie in the unusually deep binding region, the scientists report.

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Study reveals first genetic step necessary for prostate cancer growth- (Yahoo News-01/09/2004)

A new study from Fred Hutchinson Cancer Research Center reveals what may be the earliest step in the development of prostate cancer. The finding could open the door to new tests that predict whether the cancer will become aggressive and the development of treatments to prevent the condition from progressing. The study, published in the Sept. 1 issue of Cancer Research, found that when mice are engineered to lose a single copy of a gene called Rb in their prostate, they develop a precancerous condition analogous to the earliest stages of human prostate cancer. Importantly, in the absence of additional genetic defects, the mice do not develop full-blown prostate cancer.

This suggests that the loss of Rb in prostate cells could be the initial spark that in some men eventually leads to prostate cancer, said senior author Norman Greenberg, Ph.D., a member of Fred Hutchinson's Clinical Research Division. "Finding the loss of Rb is like seeing smoke," he said. "We now need to figure out the genetic predictors for fire."

To identify genetic events that cause early-stage prostate cancer, Greenberg and colleagues focused on the Rb gene. The gene is known to be defective in a variety of cancer types, including up to 60 percent of human prostate cancers. Rb is a member of a family of genes known as tumor suppressors, which normally work to keep cells dividing at a healthy pace. Cells with defective or missing tumor suppressors lose their brakes on cell division, a hallmark of cancer. The researchers developed a system using mice that were genetically engineered to self-destruct one or both copies of its Rb gene in prostate cells. The important difference between these mice and the standard gene knock-out strategy is that the Rb gene stays intact in all other tissues of the animal, a situation that closely resembles how genes are inactivated or lost in cancers that occur sporadically in humans.

The scientists found that upon losing even one copy of the Rb gene in prostate cells, mice developed a condition known as focal hyperplasia, characterized by precancerous growths. Nearly a year after they formed, the growths did not become cancerous. "This suggests to us that loss of a single copy of Rb can initiate this excess cell growth but is not sufficient for cancer to develop," Greenberg said. "Perhaps the most significant finding was that loss of the second copy of Rb – an event previously thought to be essential for tumor progression – did not appear to accelerate the disease. Losing one copy was enough to get things going."

While Greenberg had previously demonstrated that combined loss of Rb and related proteins and the p53 tumor suppressor would predispose mice to develop aggressive prostate cancer, the role of Rb in tumor initiation remained enigmatic. Further research is needed to determine which secondary mutations can push these early stage growths into prostate cancer. Greenberg said that tests to distinguish between men who only have Rb mutations and those who have acquired additional genetic defects could help doctors decide when or whether aggressive treatment is warranted. "Right now, there is no way to absolutely predict at an early stage whether a man's prostate cancer is slow-growing and non-lethal, meaning that many men receive unnecessary treatment that can cause serious side effects," he said.

Scientists have had a difficult time establishing the causal relationship between genes and cancer, Greenberg said. "We've addressed this by using a mouse system that allows us to selectively eliminate genes in the epithelial cells of the prostate. Our experimental approach allows us to closely mimic what happens in man and gives us a glimpse into the natural history of the disease that we haven't had before." Greenberg developed a widely used genetically engineered strain of mice that develops prostate cancer at the Baylor College of Medicine prior to joining Fred Hutchinson in January. "These models represent a new frontier in cancer research because they give us a better insight into what specific genes really do in a live mammal," he said. "The mice give us a highly reproducible glimpse at the earliest forms of cancer – those rarely seen in the clinic – and therefore can be used to develop new markers for detection as well as new strategies for prevention and early intervention."

Prostate cancer is the second leading cause of death for men in the United States. This year, more than 230,000 men will be diagnosed with the disease, in large part due to widespread screening with the prostate-specific antigen, or PSA, test. The test has been controversial because it cannot distinguish between men who have non-progressing forms of the disease that may never cause harm and those who have aggressive cancers that require treatment. Researchers are eager to develop tests that can stratify early stage prostate cancers by their likelihood to worsen, an achievement that could spare many men from unnecessary surgery or radiation therapy.

With this in mind, Greenberg said his next goal is to identify the additional mutations - such as occur in p53 or other tumor suppressor genes - that must collaborate with Rb to drive the benign condition to cancer. Ideally, blood or other simple tests to detect these mutations could be developed that reveal predictive information about a man's type of cancer well before he is in danger. "The idea is to set the bar for detection as early as possible," Greenberg said. "Ideally, we'd hope that a man diagnosed at an early age with prostate cancer could be assured that his cancer wasn't likely to progress or that he needed early intervention that could save his life."

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Protein Prompts Spread of Prostate Cancer-(HealthDayNews -23/08/2004)

 A protein called hepsin promotes the spread of prostate cancer by causing disruption of tissue organization, says a study in the August issue of Cancer Cell. This finding could lead to the development of new drugs that inhibit hepsin and slow prostate cancer's spread. Scientists at the Fred Hutchinson Cancer Research Center in Seattle created mice with elevated hepsin levels in the prostate gland and found these mice had marked tissue disorganization of the prostate gland, specifically in a structure called the basement membrane. These mice developed more advanced tumors and had more spread of cancer to the liver, lung and bone.

"We have found that increase in hepsin expression leads to disorganization of the basement membrane and promotes primary prostate cancer progression and metastasis," researcher Dr. Valeri Vasioukhin said in a prepared statement."Since hepsin is an enzyme, it should be relatively easy to develop drugs specifically inhibiting hepsin activity. Previous research demonstrated that hepsin is not critical for normal cells within the body and, therefore, inhibition of hepsin with drugs is unlikely to have significant side effects," Vasioukhin added.

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Exercise May Beat Fatigue in Prostate Cancer-(Reuters Health -18/08/2004)

Staying active through moderate walking may help prevent fatigue in men undergoing radiation therapy for prostate cancer, a UK study shows. Cancer patients commonly develop fatigue as the stress of the illness and the physical effects of treatment take their toll. It's common for patients undergoing treatment to be told to take it easy, and some may self-impose limits on their daily activities, according to the study's lead author Dr. Phyllis M. Windsor.

But in her team's study of 66 men with cancer confined to the prostate gland, those who were physically active during their month of radiation treatment showed no substantial increase in fatigue. The same was not true of patients in the non-exercising "control" group, according to findings published in the August issue of the journal Cancer. The findings are in line with research with women undergoing radiation and chemotherapy for breast cancer, noted Windsor, a cancer specialist at Ninewells Hospital in Dundee, Scotland. It's thought, she told Reuters Health, that such results "potentially apply to all groups of patients with cancer."

While rest may be the intuitive response to fatigue, too much inactivity can make the problem worse. Long periods of rest, Windsor said, may de-condition muscles and roll back a person's capacity for exercise, making even routine daily tasks tough to tackle. Exercise, on the other hand, keeps muscles conditioned, so that everyday activities require less effort and are less taxing on the body. In addition, Windsor pointed out, research suggests that exercise combats depression, which can alter patients' perceptions of fatigue.

For the current study, the researchers randomly assigned 66 men with localized prostate cancer to either an exercise group or a control group. The exercisers walked at a moderate pace for 30 minutes, three days per week; patients in the control group were not discouraged from performing their usual activities, but were told to rest if they became tired. After four weeks of radiation therapy, men in the control group were had greater fatigue than they did before treatment; and one month later, these patients were still showing signs of weariness. In contrast, exercisers showed no significant increase in fatigue at any point during the study, according to the researchers. Windsor said she and her colleagues are planning a larger study to see if walking or, for patients who cannot walk, chair-based exercises can counter fatigue in patients with a range of cancers, including prostate, cervical, uterine, bladder and kidney cancers.

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Study narrows search for genes placing men at increased risk for prostate cancer-(Yahoo News-18/08/2004)

Scientists at the Translational Genomics Research Institute (TGen), Johns Hopkins Medical Institutions, the National Institutes of Health, The University of Michigan and five other research institutes world-wide announced today the findings from the largest study of the genetics of prostate cancer undertaken to date. Results have zeroed in on three different regions of the genome containing genes that may make men more vulnerable to this common cancer. Prostate cancer is the second-leading cause of cancer death in US men. The findings appear in the August 18 issue of the Journal of the National Cancer Institute. The researchers are currently scouring those genome regions, culled from more than 400 cancer-prone families, to identify specifically which genes lead to increased prostate cancer susceptibility.

"This study will help us predict better who is at the highest risk for this disease," says the paper's lead author, Dr. Elizabeth Gillanders, a scientist at the National Institutes of Health in Bethesda, MD. "If we could identify men with susceptibility genes, we can target our surveillance to them and identify their cancers much earlier. Early-stage treatment is far more beneficial in prostate cancer," she says. In addition, she noted, prostate cancers in men who possess susceptibility genes tend to be more aggressive--and more often fatal--than prostate cancers in men who are not genetically prone to the disease. "This study focuses and intensifies the hunt for genes that increase a man's risk of prostate cancer," says the paper's senior author, Dr. Jeffrey M. Trent, Scientific Director of TGen in Phoenix, Arizona. "We needed this sort of massive study in order to have the power to target important genome regions."

"The difference between this paper and previous work on the genetics of prostate cancer is the number of families studied," says Dr. William B. Isaacs, of the Johns Hopkins University in Baltimore, MD, principal investigator for the project. "There has been much confusion and difficulty in trying to figure out where we should be looking for these genes." Today's paper reports on data from approximately 2,000 individuals from over 400 families.

"The large number of prostate cancer families utilized in this study allowed us to overcome the challenges we have faced in this field for the past few years," says Dr. Jianfeng Xu, one of the lead authors on the paper and a researcher at Wake Forest University School of Medicine. "This study shows that hereditary prostate cancer genes exist and demonstrates that by working together, teams of researchers are able to locate these genes. These results give us a renewed confidence in our search for prostate cancer genes."

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Study: Test predicts prostate cancer's aggression-(AP-08/07/2004) 

Prostate cancer is much more likely to kill if a man's PSA level rises rapidly before the cancer is even diagnosed, according to a study that suggests a new and far more meaningful way of looking at PSA test results. The finding could help patients and doctors make the often difficult decision of whether to undergo surgery or merely wait and watch. The PSA test is widely used to diagnose prostate cancer by measuring levels of a substance called prostate-specific antigen in the blood. Up to now, doctors have focused largely on the PSA level itself, and not on how it changes over time. But researchers at Brigham and Women's Hospital and elsewhere found how fast PSA level increased in the year before prostate cancer was diagnosed predicts which tumors are deadly nearly 10 times better than the PSA level itself. "The study is pretty definitive," said lead researcher Dr. Anthony D'Amico, a radiation oncologist at Brigham and professor of radiation oncology at Harvard Medical School. "It's not the level of PSA that matters, it's the change from year to year." The finding underscores the importance of getting regular PSA screenings, so that doctors can spot trends.

When doctors find prostate cancer, they often recommend "watchful waiting" over prostate-removal surgery, because the operation can cause impotence and incontinence and because some prostate tumors are so slow-growing that men die of something else before the cancer kills them. But most men do not want to wait, so doctors are seeking better ways of predicting which tumors will be lethal.

PSA levels alone are not always reliable. A recent study found the tests missed about 15 percent of prostate cancers in older men whose readings were supposedly normal -- that is, at or below a count of 4. The new study, reported in Thursday's New England Journal of Medicine, followed 1,095 men, 65 years old on average, who had prostate cancer; they received PSA screenings at least once a year and underwent prostate surgery between 1989 and 2002. Twenty-eight percent of the men whose level rose more than 2 points the year before diagnosis died of prostate cancer within seven years -- despite having the gland and adjacent lymph nodes and seminal vesicles surgically removed. D'Amico said the findings make clear which patients need aggressive treatment, but not which ones can safely be monitored through repeated testing. 

PSA is a protein that helps liquefy semen for ejaculation. An elevated PSA level can indicate benign prostate enlargement or prostate cancer. So when a man is found to have an elevated PSA level, doctors do a biopsy, withdrawing cells from the gland by needle for examination under the microscope for signs of cancer. Guidelines call for annual PSA tests beginning at age 50 - or 45 for men with a family history of prostate cancer. D'Amico said a baseline PSA level should be determined at age 35 to spot changes. 

Dr. Mark Jordan, professor and chief of urology at University of Medicine and Dentistry of New Jersey in Newark, said he believes the initial PSA level, and the percentage increase, are just as important as the rate of increase, or PSA velocity, but there are not enough guideposts for deciding on surgery. "We're not even sure if prostate cancer surgery prolongs life," said Jordan.

Dr. Howard Parnes, chief of the National Cancer Institute's prostate and urological cancer research group, said a high PSA velocity indicates substantial risk of relapse after surgery and death. But he said larger studies with longer follow-up are needed. Parnes and D'Amico said the PSA velocity can be used now to identify which high-risk men could participate in studies of such treatments as radiation, hormones to suppress testosterone and cancer drugs that could be given in addition to surgery.

Prostate cancer is the No. 2 cancer killer among men, with an estimated 30,000 deaths and 230,000 new cases each year, according to the American Cancer Society. Despite that, only about 60 percent of American men over 50 have had a PSA screening. Men have a one-in-six lifetime risk of getting prostate cancer. However, the death rate has fallen nearly 20 percent since the PSA test became widely used in the mid-1990s, a drop attributed to both earlier detection and better treatment.

Dr. William J. Catalona of Northwestern Memorial Hospital, who worked with D'Amico and helped develop the PSA test to determine risk of prostate cancer, said he thinks a biopsy should be done once the PSA level hits 2.5 or PSA velocity reaches 0.75 -- as the National Comprehensive Cancer Network recently recommended.

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 Tools for prostate-cancer recovery-(Yahoo News-20/07/2004)

Psychologist teams with doctor to help patients and their families cope with treatment side effects As many prostate-cancer survivors have discovered, the lifesaving benefits of surgery, radiation and hormone therapy can come with a cost. All three treatments may bring on sexual dysfunction and urinary incontinence. In addition, by depriving the body of testosterone, long-term hormone therapy can blunt a man's sex drive, sap his energy and trigger mood swings.

These and other quality-of-life adjustments affect patients as well as their partners and aren't easily resolved in the doctor's office, says Tia Higano, M.D., a University of Washington (UW) prostate-cancer specialist and associate in clinical research at Fred Hutchinson. Higano decided she wanted to do more to help. She found her answer in UW psychologist Sylvie Aubin, Ph.D. Aubin sits in on Higano's patient consults and offers prostate-cancer patients and their partners a "toolbox" of strategies to cope with challenges that are often hard to talk about. They see their patients at the Seattle Cancer Care Alliance, a patient-care partnership of Fred Hutchinson, the UW and Children's Hospital and Regional Medical Center located on the Fred Hutchinson campus. "Men can live a long time after treatment for prostate cancer, and they deserve to have a good quality of life," said Aubin, an acting instructor in the UW Department of Psychiatry and Behavioral Sciences. "But it's often very hard to get men to open up about these problems, which is the first step. Once I open the door for them to do that, my role is to be a 'tool person' -- to provide patients and partners with a collection of strategies to help them deal with these challenges." Aubin and Higano plan to measure the benefits of those interventions in the coming months in a research study.

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Today's Prostate Cancer Treatments More Aggressive, Successful Says American Society for Therapeutic Radiology and Oncology-(US Newswire-14/07/2004)

In recent years, doctors have become more willing to treat prostate cancer more aggressively with radiation therapy, and as a result, more patients are being cured of their cancer, according to a new study published in the July 15, 2004, issue of the International Journal of Radiation Oncology, Biology, Physics, the official journal of ASTRO, the American Society for Therapeutic Radiology and Oncology. A 1999 Patterns of Care survey reviewing the records of more than 550 patients from 58 institutions across the United States shows that in comparison to surveys from 1989 and 1994, radiation oncologists are using higher doses of external beam radiation therapy to treat both earlier stages and more aggressive forms of prostate cancer. In 1999, 45 percent of prostate cancer patients were treated with higher doses of radiation therapy compared to 3 percent in both 1989 and 1994.

In the study, researchers learned that the results of clinical trials have persuaded many radiation oncologists today to add androgen deprivation therapy to radiation therapy to treat more aggressive or well-established cancers. Further, there has been a significant increase in the use of CT-based treatment planning and conformal radiation therapy for treatment delivery. "This is an important study because it looks at changing trends over many years in the use of radiation therapy for curing prostate cancer in the United States," said Michael J. Zelefsky, M.D., lead author of the study and a radiation oncologist at Memorial Sloan-Kettering Cancer Center in New York. "After careful analysis, we have learned that in general, more radiation oncologists are applying the results of clinical trials, which have taught us to use higher dose levels of radiation and integrate hormone therapy in conjunction with radiation therapy to achieve more successful outcomes for prostate cancer patients. In short, the trends are demonstrating more precise delivery of high dose treatment."

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Alternative hormone-blocker reduces side effects in prostate cancer patients-(Yahoo News-28/06/2004)

An alternative way of blocking androgen activity in prostate cancer patients produces fewer side effects and may be a better choice than standard hormone therapy for some patients. In the July issue of the Journal of Clinical Oncology, researchers from the Massachusetts General Hospital (MGH) describe how patients taking bicalutamide, which inhibits androgen activity by binding to the hormones' receptors, had improved bone density and reported fewer unpleasant side effects than did those taking leuprolide, a traditional form of hormone therapy that markedly lowers androgen levels. "The differences between the two groups were dramatic; bone mineral density increased among men taking bicalutamide while men in the leuprolide group lost bone," says Matthew Smith, MD, PhD, of the MGH Cancer Center, who led the study.

Since the male hormones called androgens can accelerate the development of prostate cancer, reducing their activity is a standard part of treating the disease. Most commonly this is done with drugs like leuprolide, called gonadotropin releasing hormone (GnRH) agonists, that stop the body's production of all sex hormones. However, totally blocking hormone activity can lead to potentially serious side effects such as loss of bone density, which increases the risk of fractures. Earlier studies by this MGH research team also showed that GnRH-agonist treatment often leads to unwanted weight gain and increased body fat. Because bicalutamide blocks androgen activity in a way that does not reduce hormone levels in the blood, the research team wanted to see if using a single-drug treatment plan might avoid or reduce side effects. Earlier research had shown that bicalutamide alone is as effective as GnRH agonists for men with locally advanced prostate cancer.

The investigators enrolled 51 men with nonmetastatic prostate cancer who were randomly assigned to receive either bicalutamide or leuprolide treatment for one year. Although the participants knew which treatment they received, since the drugs are adminstered differently, those who gathered and analyzed the study's data did not know which patients were in which group. At the end of the study period, blood levels of testosterone and the female hormone estradiol had risen significantly in the bicalutamide group but fallen in those receiving leuprolide. Bone mineral density, which decreased in the leuprolide group, had increased in participants receiving bicalutamide. While both groups had increases in body fat and decreased lean body mass, those changes were more pronounced in those receiving leuprolide. And unpleasant side effects - such as hot flashes, fatigue and sexual effects - were reported less frequently in men taking bicalutamide. "Bicalutamide monotherapy may be an attractive alternative to standard hormone therapy for some men with non-metastatic prostate cancer," says Smith, who is an assistant professor of Medicine at Harvard Medical School. While bicalutamide is approved as monotherapy for prostate cancer in 55 countries, in the U.S. it is only approved in combination with GnRH-analog therapy.

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Prostate cancer study boosts radiation therapy-(Yahoo News-26/06/2004)

Prostate cancer patients who receive radiation therapy within six months of surgery typically live longer than patients who don't receive early radiation treatment, a new Italian study finds. "Our results show that radiation therapy after prostate surgery helps limit the chances that the cancer will recur, allowing patients to live longer,' said Dr. Cesare Cozzarini, a radiation oncologist at San Raffaele H. Scientific Institute in Milan, and the study's principal investigator. "To my knowledge, this is the largest study of its kind completed at a single institution,' he added.

The researchers examined the records of 415 men with prostate cancer who underwent surgery to remove their prostate and surrounding lymph nodes between 1986 and 1999 at the institute. Two groups of postsurgical patients were studied -- one group included men who received external beam radiation therapy within six months of their prostate operation, and the other included men whose physicians followed them over time and provided radiation therapy only if their cancers showed signs of returning. None of the men whose records were studied had metastatic disease -- that is, cancer in areas of the body other than the prostate. After eight years of follow-up, the survival rate for men receiving early radiation therapy was 69 percent, compared to 31 percent for those who had radiation therapy more than six months after their surgeries or not at all. The researchers also found that the disease remained localized in the prostate for 93 percent of the patients in the early radiation therapy group, compared to 63 percent in the other group. The risk of death from localized prostate cancer was also significantly lower for men receiving postsurgical early radiation therapy.

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Thalomid(R) in Major Peer-Reviewed Journal Publication of Clinical Data From Randomized Phase II Trial in Androgen-Independent Prostate Cancer-(Yahoo News-01/07/2004)

Celgene Corporation today announced the results of a randomized Phase II trial conducted by the National Cancer Institute (NCI). This trial used thalidomide in combination with docetaxel (taxotere) versus docetaxel alone in patients with metastatic androgen-independent prostate cancer (AIPC), and is published in the July 1, 2004 issue of the Journal of Clinical Oncology (JCO), a major peer-reviewed journal.

Prostate cancer is the most diagnosed cancer in American men and the second leading cause of cancer death. During 2004, an estimated 220,900 men will have prostate cancer diagnosed, and 32,500 men will die of this disease in the United States. This Phase II clinical study investigated the combination of docetaxel at 30mg/m2 intravenously every week for three weeks plus thalidomide at 200 mg orally each day versus docetaxel at 30mg/m2 intravenously every week for three weeks in patients with AIPC. The data from this clinical study reported that the proportion of patients with a greater than 50% decline in prostate-specific antigen (PSA) was higher in the thalidomide/docetaxel group, 53% in the combined group and 37% in the docetaxel-alone arm. The median overall survival in the thalidomide plus docetaxel group was 28.9 months compared to 14.7 months in the docetaxel-alone group. At 18 months, overall survival in the thalidomide/docetaxel group was 68.2% compared to 42.9% in the docetaxel-alone arm (P =0 .11 for the overall difference). The median progression-free survival in the thalidomide/docetaxel group was 5.9 months compared to 3.7 months in the docetaxel-alone group (P =0 .32). "This Phase II clinical data demonstrated that thalidomide in combination with docetaxel may be a future option in the clinical treatment of androgen-independent prostate cancer," said Dr. Sol J. Barer, Ph.D., President and Chief Operating Officer of Celgene Corporation. "Based on the preliminary results, from this National Cancer Institute study, we will advance clinical investigation of thalidomide, and other Celgene immunomodulatory agents such as REVLIMID and ACTIMID, in this severe and life-threatening form of cancer."

About the Phase II Study This was an open-label, randomized, phase II study of docetaxel plus thalidomide versus the docetaxel alone in patients with metastatic AIPC. A total of 75 patients were enrolled in this trial, with 25 patients in the docetaxel alone arm and 50 patients in the combination arm. Seventy-five patients with chemotherapy-naive metastatic AIPC were randomly assigned to receive either docetaxel 30 mg/m2 intravenously every week for 3 consecutive weeks, followed by a 1-week rest period (n = 25); or docetaxel at the same dose and schedule, plus thalidomide 200 mg orally each day (n = 50). PSA consensus criteria and radiographic scans were used to determine the proportion of patients with a PSA decline, and time to progression. After a median potential follow-up time of 26.4 months, 40 patients are currently alive. The proportion of patients with a greater than 50% decline in PSA was higher in the thalidomide/docetaxel group (53% in the combined group, 37% in the docetaxel-alone arm). The median overall survival in the thalidomide plus docetaxel group was 28.9 months compared to 14.7 months in the docetaxel-alone group. At 18 months, overall survival in the thalidomide/docetaxel group was 68.2% compared to 42.9% in the docetaxel-alone arm (P =0 .11 for the overall difference). The median progression-free survival in the thalidomide/docetaxel group was 5.9 months compared to 3.7 months in the docetaxel-alone group (P =0 .32). Toxicities in both groups were manageable after administration of prophylactic low-molecular-weight heparin was used to prevent venous thrombosis. The combination of thalidomide/docetaxel was clinically tolerated.

Safety Notice If thalidomide is taken during pregnancy, it can cause severe birth defects or death to an unborn baby. Thalidomide should never be used by women who are pregnant or who could become pregnant while taking the drug. Even a single dose, one capsule (50 mg, 100 mg and 200 mg), taken by a pregnant woman can cause severe birth defects. Because thalidomide is present in the semen of male patients, males receiving thalidomide must always use a latex condom during sexual contact with women of childbearing potential even if he has undergone a successful vasectomy.

Thalidomide can only be marketed under a special restricted distribution program. This program is called the "System for Thalidomide Education and Prescribing Safety" (S.T.E.P.S.(R)). Under this program, only registered prescribers and pharmacists may dispense the drug. In addition, patients must be advised of, agree to and comply with the requirements of S.T.E.P.S. Thalidomide is known to cause nerve damage that may be permanent. Peripheral neuropathy is a common, potentially severe, side effect of treatment with thalidomide that may be irreversible. Decreased white blood cell counts, including neutropenia, have been reported in the clinical use of thalidomide. In placebo controlled clinical trials of HIV-seropositive patient populations, there have been reports of increased plasma HIV RNA levels associated with thalidomide therapy. The most common adverse events observed in clinical use in ENL and HIV-seropositive patient populations are rash, maculo-papular rash, drowsiness/somnolence, peripheral neuropathy, dizziness/orthostatic hypotension, neutropenia, and increased HIV-viral load. Patients should be advised about these associated adverse events and routinely monitored by a physician during treatment with thalidomide.

About THALOMID THALOMID (thalidomide), manufactured by Celgene Corporation, received U.S. Food and Drug Administration (FDA) clearance on July 16, 1998 for the acute treatment of cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL) and as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence. Thalidomide is not indicated as monotherapy for ENL treatment in the presence of moderate to severe neuritis. Thalidomide currently has a pending regulatory application (NDA) under review by the Food and Drug Administration (FDA) to confirm efficacy and safety for use in multiple myeloma, thalidomide is not presently indicated or approved by the FDA for use in this disease or any other related cancer.

About Prostate Cancer: Prostate cancer is the most diagnosed cancer in American men and the second leading cause of cancer death. Prostate cancer is twice as common and has more than twice the mortality rate in African-American men than in Caucasian men. The 5-year survival rate for patients whose cancer is caught while still confined to the prostate is 99% while the 5-year survival rate for those diagnosed with distant (metastatic) disease is 30.9%. In the U.S. alone, nearly 220,900 men will be diagnosed with prostate cancer this year equaling one man diagnosed every three minutes. It is estimated that more than 32,500 men in the U.S. will die of prostate cancer. Prostate cancer affects one in eight American men.

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Popular Painkiller May Slow Prostate Cancer Cox-2 Inhibitors -- Such as Celebrex -- May Delay, Prevent Cancer Progression-(Yahoo News-11/06/2004)

The commonly prescribed painkiller Celebrex may slow prostate cancer growth, new research shows. Drugs known as Cox-2 inhibitors, including Celebrex, have been shown to have anti-tumor effects on a variety of different cancer tissues, including colon, breast, lung, and prostate cancers, explains researcher J. Eric Derksen, MD, a urologist with the University of North Carolina at Chapel Hill. Cox-2 inhibitors (commonly used to treat arthritis) relieve pain, inflammation, and swelling by blocking the body's production of an enzyme called Cox-2. These drugs, which also include Bextra and Vioxx, are less irritating on the stomach lining than earlier versions of anti-inflammatory drugs, like ibuprofen.

Recent research involving men treated for prostate cancer has shown especially promising results, says Derksen, who presented his findings at the American Society of Clinical Oncology's annual meeting this week in New Orleans. In his study, Derksen enrolled 24 men who had rising PSA (prostate-specific antigen) levels, a marker for prostate cancer growth, despite treatment with radiation therapy or prostate removal surgery. The men took either 400 milligrams or 800 milligrams of Celebrex for one year. Their PSAs were checked at several points during that year. Celebrex had a positive effect on nearly all (92%) of the men after three months, reports Derksen. Overall, PSA declined in eight of the men and remained the same in three. The rise in PSA levels slowed in 11 men, indicating that their prostate cancer was growing more slowly. The two remaining men had no improvement at three months but the rise in their PSA levels slowed by one year.

It's a hopeful finding: The other option involves shutting down production of male sex hormones -- usually with medication -- which has not proven successful in slowing prostate cancer or improving a man's chances of survival. Also men in the early stages of prostate cancer recurrence, such as the men in this study with rising PSA levels, usually have no symptoms. Therefore, shutting down production of male sex hormones could unnecessarily expose them to side effects, say the researchers. "These results show that Cox-2 inhibitors may help delay or prevent [prostate cancer] progression in these patients," he writes.

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Soy Product May Help Fight Prostate Cancer-(ET-13/06/2004)

Cancer researchers at U.C. Davis are testing a new compound derived from soy beans and shitake mushrooms as a possible new tool to battle prostate cancer. Genistein concentrated polysaccharide (GCP) is already widely used as a complementary therapy for prostate cancer in Japan and Korea. The Davis scientists are testing GCP on men in the so-called watchful waiting stage of prostate cancer. "We're only going to treat patients who are in active surveillance. In other words, they would diagnose the prostate cancer but do not want any active treatment," Dr. Ralph deVere White told KCBS reporter Patti Reising.

White is director of the U.C. Davis Cancer Center, as well as a professor and chair of urology at U.C. Davis School of Medicine. "We think this will allow us to absolutely prove whether this really is a reasonable treatment for patients who are diagnosed with a very low grade, low-volume prostate cancer," said White. A company which manufactures and distributes GCP, Amino Up Chemical Co., Ltd. of Japan, sponsored the research. "I give great credit to them, White said. "They're really allowing us to test it." White said the initial results have looked promising, although the university is still searching for other men willing to volunteer in the study. "It does look like the mixture has some benefit, he said.

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Selenium May Protect Against Prostate Cancer-(Reuters Health-04/05/2004)

Use of supplements containing selenium may reduce the risk of advanced prostate cancer, new research suggests. The fact that no effect was seen against early prostate cancer suggests that selenium works by slowing cancer progression rather than by preventing it all together. The current study is one of several recent looks at the link between selenium levels and prostate cancer. "Our study is the largest in terms of the (number of participants) and the follow-up period," lead author Dr. Haojie Li, from Harvard Medical School in Boston, told Reuters Health. As reported in the Journal of the National Cancer Institute, the researchers analyzed data from men enrolled in the Physicians' Health Study.

When the study began, the men, who were cancer-free at the time, gave blood samples that were tested for selenium among other things. Selenium levels from 586 men who later developed prostate cancer were compared with levels from 577 similar men who didn't develop prostate cancer. Men with the highest selenium levels were 48 percent less likely to develop advanced prostate cancer than men with the lowest levels. Moreover, this association was observed for men diagnosed before and after PSA testing to detect early prostate cancer came into widespread use in October 1990. High selenium levels were linked to a reduction in the overall risk of prostate cancer, Li said. "However, on further analysis, only the association with advanced cancer," was statistically significant, not early cancer. A specially designed study, "known as the Selenium and Vitamin E Cancer Prevention Trial (SELECT), is underway," Li noted, and this should definitively answer whether selenium use is beneficial in preventing prostate cancer.

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High Hormone Levels Linked to Prostate Risk-(Reuters-09/05/2004)

Men over 50 who have higher levels of testosterone have a higher risk of prostate cancer, U.S. researchers reported. The findings may mean that men should be cautious about a new kind of treatment called testosterone replacement therapy, being tested in older men who see a decline in general health and vigor. A study of more than 750 men showed those with the highest levels of free testosterone in the blood were the most likely to have prostate cancer. "Since testosterone replacement therapy increases the amount of free testosterone in the blood, older men considering or receiving testosterone replacement should be counseled as to the association until data from long-term clinical trials becomes available," said Dr. Kellogg Parsons, a urologist at Johns Hopkins University who led the study, said in a statement.

The association between free testosterone and prostate cancer risk in older men was not affected by height, weight, percent of body fat or muscle mass, Parsons told a meeting of the American Urological Association in San Francisco. A second study presented at the same conference found that obese men may be more likely to see their prostate cancer come back after surgery. Another Johns Hopkins team found that obese men are more likely than men with normal weight to have high levels of prostate specific antigen, or PSA. PSA is produced by prostate cells and is overproduced when the prostate becomes cancerous. "Our results show that moderately and severely obese men were at an increased risk for high PSA levels after surgery and therefore are likely to have prostate cancer recurrence," said Dr. Stephen Freedland, who led the study. His team studied 1,106 patients treated at five Veteran's Administration and military hospitals across the country. "Our findings add to the burgeoning list of chronic and deadly diseases associated with obesity and underscore the importance of this major public health problem," Freedland said.

Obesity is also linked with pancreatic, breast and colon cancer, as well as heart disease and diabetes. Prostate cancer affects 221,000 American men a year and kills 29,000.

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Long-Term Cancer Survival Data Utilizing ONCURA's OncoSeed(TM) Reinforces Brachytherapy's Position as Standard of Care for Treating Prostate Cancer- (PRNewswire-28/04/2004)

As the global leader in minimally invasive prostate cancer treatment, ONCURA(TM) is committed to research and development that results in improved outcomes for patients treated with prostate brachytherapy. Fifteen-year data exclusively utilizing ONCURA's OncoSeed (Iodine-125 Seeds) were recently presented by John Blasko, MD, Medical Director of the Seattle Prostate Institute at the Institute's 7th annual Seattle Prostate Institute meeting. "At fifteen years after Iodine-125 brachytherapy, only 4% of patients had died from prostate cancer," said John Blasko. "The release of this data further confirms brachytherapy as a leading prostate cancer treatment option." "The presentation of long-term survival data that's only available for ONCURA's Iodine-125 products will encourage other physicians to offer prostate brachytherapy to their patients," said John Jeans, Chairman of ONCURA. He added, "Advances such as ONCURA's RAPID Strand(TM), which is routinely used by the Seattle Prostate Institute, are expected to improve results even further."

Long-term data supporting prostate brachytherapy with RAPID Strand were presented at the European Association of Urology meeting in Vienna. Mr. Stephen Langley, Consultant Urologist at St Luke's Cancer Centre, Guildford, UK, presented results of their five-year follow-up, with 93% of patients disease free at this time. These results indicate that prostate brachytherapy has now become a routine and successful option for patients in Europe as well as the US. "Our commitment to prostate brachytherapy is exemplified by our continued support of centers of excellence that evaluate and present long-term data," said James McGlone, CEO and President of ONCURA.

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Online tool estimates long-term chance of surviving prostate cancer -(Yahoo News-13/04/2004)

A study just completed by researchers at the Josephine Ford Cancer Center has resulted in the most comprehensive long-term prostate cancer survival model available to date. An interactive version of the survival model is available online at prostatecalculator.org. Patients and doctors who visit the site can obtain a personalized 10-year survival estimate based on age, race, a few clinical measures, and the kind of treatment being pursued. Once data have been entered, a simple mouse-click provides the prognosis.

Dr. Ashutosh Tewari, with the Josephine Ford Cancer Center (Detroit, MI) worked with investigators at ANNs in CaP (Denver, CO) to retrospectively identify a cohort of 1,611 patients with clinically localized prostate cancer as well as 4,538 age, race, and co-morbidity (those with additional diseases) matched controls.Based on demographic and clinical variables, propensity risk scoring was used to develop survival probability estimates for both patients and controls. Because the calculator, and the companion look-up tables published in the April issue of the Journal of Urology, provide a comparison with men with similar characteristics but who do not have prostate cancer, users receive a realistic estimate of the impact of prostate cancer on long-term survival.

Prostate cancer is the most common solid-organ male malignancy diagnosed in the United States, with an estimated 189,000 new cases each year. Currently, African-American men have the highest incidence of prostate cancer in the world (137 per 100,000 per year), and are 2.5 times as likely to die as whites. While the reason for this is not known, some research suggests that black men are often diagnosed at later disease stages. Dr. Tewari adds, "Our research indicates that African-American men also tend to undergo less aggressive treatment than whites, and additional studies by our group suggest that if they received the same treatments, their prostate cancer survival rates would be much closer to those of whites." The study also showed that a man's level of co-morbidities can have as much or more of an impact on his chances of long-term survival than his prostate cancer alone.

This new prostate cancer survival model is the most comprehensive to date because it provides an estimate of the likelihood of survival taking into account a patient's age, race, comorbities, and treatment type. According to Dr. Tewari, "While the study was not a randomized controlled trial comparing surgery, radiation therapy, and watchful waiting, the method we used has been shown to eliminate much of the bias introduced with a non-randomized study design. And the inclusion of a large, matched control group is a great strength of our study." While the study, which was awarded a first prize by the American Urological Association, adds to the knowledge of how co-morbidities and race affect the long-term survival of men with prostate cancer, an additional benefit is that it prompted Dr. Tewari's team to ask and seek answers to new questions: Why do black men receive less aggressive treatment than whites? Are black men choosing less aggressive treatment themselves or are their doctors suggesting the treatment? And, finally, is it worthwhile for men with additional diseases to treat their prostate cancer? No personal information is collected and patient privacy is respected. The site does not promote particular doctors or specific treatments.

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Prostate Cancer Surgery Helps with Urination-(Reuters Health-22/04/2004)

Men with localized prostate cancer have a number of treatment options, all with pros and cons. On the plus side for surgical removal of the prostate gland, the procedure can also help some men urinate better, new research indicates. In contrast, other treatments, such as radiation therapy, may actually make urination worse. In agreement with a report released earlier this month, the current findings suggest that when treatments are equally effective in terms of survival, quality-of-life issues become paramount in selecting one prostate cancer therapy over another. The current results are based on a study of 50 men with urination problems who were later found to have prostate cancer. All of the patients underwent radical prostatectomy, as the surgical procedure is called. A variety of measures were used to evaluate urinary function before and after surgery.

Dr. V. Kumar, from the Royal Hallamshire Hospital in Sheffield, UK, and colleagues found that for men with moderate to severe urinary symptoms, surgery resulted in significant improvements in the strength of the urine stream and in the ability to empty the bladder. These men also reported an improvement in their quality of life. On the other hand, surgery did not improve urination in men with mild symptoms, the team reports in the medical journal BJU International. Six months after the procedure, 39 men had essentially normal urinary function, 10 had mild leakage, but required no pads, and 1 patient required pads during heavy physical exertion. "This study confirms that radical prostatectomy provides major benefits beyond cancer control in men with pre-existing bothersome lower urinary tract symptoms," the authors state. "This is important in counseling patients about treatment options for clinically localized prostate cancer."

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Vegetable Fiber Tied to Lower Prostate Cancer Risk-(Reuters Health-14/04/2004)

Men who eat their veggies may be less likely than others to develop prostate cancer, a new study suggests. Among more than 1,700 men with and without prostate cancer, those who ate the most fiber -- particularly from vegetable sources -- had a lower risk of developing the disease, Italian researchers found. The benefit was "moderate," they report in the International Journal of Cancer, but the findings suggest that at least some forms of fiber offer prostate cancer protection. A number of studies have suggested that eating plenty of fruits and vegetables may help ward off prostate cancer, while "Western"-style diets heavy in animal fat and dairy products may increase a man's risk of the disease.

But not all studies have reached these conclusions, and the importance of diet in prostate cancer risk is still unclear. There is evidence that fiber-rich foods may lower the risk of heart disease, diabetes and possibly certain cancers. However, studies looking at fiber and prostate cancer have generally yielded "null" findings, said Dr. Claudio Pelucchi, a researcher at the Mario Negri Institute for Pharmacological Research in Milan and lead author of the new study. The difference in his team's study, Pelucchi told Reuters Health, is that it broke down men's fiber intake according to the type and source of fiber. Fiber comes in two main forms, soluble and insoluble. Soluble fiber partially dissolves in water, and its food sources include vegetables, fruit, oatmeal and legumes. Insoluble fiber, which passes through the digestive system largely intact, is found in foods like whole grains, seeds and the skin on fruit.

For the study, Pelucchi and his colleagues surveyed 1,745 men between the ages of 46 and 74 about their diet and lifestyle habits. All of the men were surveyed while being treated in Milan-area hospitals between 1991 and 2002; nearly 1,300 had prostate cancer, while the rest were treated for conditions unrelated to cancer. Those with prostate cancer were asked about their eating habits during the two years before being diagnosed. Pelucchi's team found that men with the highest overall fiber intake had a slightly lower risk of prostate cancer than men with the lowest intake. When the researchers looked at specific types of fiber, vegetable fiber emerged as most protective. Men who got the most fiber from vegetables were 18 percent less likely than those who ate the least to develop prostate cancer. Fiber from fruit or grain products, specifically, was not related to a lower prostate cancer risk, but soluble fiber did appear to protect against the disease. Pelucchi pointed out that because vegetables and fruit were the chief sources of soluble fiber, it's possible that the fiber, per se, did not bestow the benefit. Other nutrients found in produce -- or the generally healthy diet and lifestyle of fiber enthusiasts -- could be at work, he said.

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