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Prostate cancer cell culture experiments support selenium and vitamin E combination treatment
In the November 1, 2008 issue of The Prostate, researchers at the University of Wisconsin report their finding that a combination of vitamin C and E administered to human prostate cancer cell cultures results in apoptosis (programmed cellular self-destruction). The finding adds support to the hypothesis that vitamin E and selenium are of value in prostate cancer prevention, which is being investigated by the twelve-year Selenium and Vitamin E Chemoprevention Trial (SELECT) of over 32,000 healthy men.
For the current study, Nihal Ahmad, PhD and colleagues added varying concentrations of alpha-tocopherol succinate (vitamin E), a form of selenium known as methylselenic acid, or both nutrients to three human prostate cancer cell lines as well as normal prostate epithelial cells. While vitamin E succinate or selenium alone modestly inhibited the growth and viability of prostate cancer cells, the combination of the two dramatically inhibited prostate cancer cell growth while having no effect on either growth or viability of normal cells.
The scientists determined that the nutrients' mechanism involves proteins that are members of the Bcl-2 family, which participate in the control of apoptosis. Apoptosis occurred in all cell lines used in the study, two of which were androgen-insensitive and defective for p53. The finding is important because prostate cancer undergoes a transition from androgen-sensitive to androgen-insensitive disease, and most prostate cancers contain both types of cells.
"We have found that the combination of vitamin E succinate and methylselenic acid was much more effective than either of the agents alone," the authors conclude. "Also, we have used low concentrations of both the agents which makes our finding more relevant to in vivo [living] settings."
Pathology: Histology: Prostate Cancer
Histological slide (H & E stain at x300) showing prostate cancer. On the right is a somewhat normal Gleason Value of 3 (out of 5) with moderately differentiated cancer. On the left is less normal tissue with a Gleason Value of 4 (out of 5) that is highly undifferentiated. The Gleason score is the sum of the two worst areas of the histological slide. (Slide by Otis Brawley)
Compound Can Distinguish Between Benign, Localized and Metastatic Prostate Cancer
Researchers have determined that a molecule produced by the body's metabolism could be used to differentiate between benign prostate tissue vs. localized and metastatic prostate cancer. They also found that this molecule, known as sarcosine, may be associated with prostate cancer invasiveness and aggressiveness. The findings were reported by researchers at the Michigan Center for Translational Pathology, Ann Arbor, and were supported by the National Cancer Institute's (NCI) Early Detection Research Network (EDRN). The research appears in the Feb. 12, 2009 issue of Nature. NCI is part of the National Institutes of Health. "Current biomarkers for detection or progression of prostate cancer are not as precise as we would like. Therefore, a more accurate indicator of cancer is of great interest," said Sudhir Srivastava, Ph.D., chief of NCI's Cancer Biomarkers Research Group. "Sarcosine and some other select metabolites may be excellent indicators of cancer progression."
Multiple, complex molecular events characterize cancer development and progression. Determining which molecular networks dictate whether cancer will be confined to the prostate or spread to other parts of the body could lead to the identification of critical biomarkers associated with prostate cancer invasion and aggressiveness.
Although many genes and proteins related to cancer have been extensively characterized by genomic and proteomic studies, little is known about metabolomic changes that mark a tumor's progression. Metabolomics, upon which this current finding is based, is the study of the unique chemical fingerprints that cellular processes leave behind, which can help scientists understand the makeup of a cell. One of the challenges that scientists currently face is integrating genomic, proteomic, and metabolomic information to give a more complete picture of living organisms and the diseases that afflict them.
Using a long-established laboratory technique called mass spectrometry, which sorts chemical compounds by their molecular weight, the researchers profiled more than 1126 metabolites from 262 clinical samples related to prostate cancer (42 tissue samples, 110 urine samples and 110 samples of blood plasma). These metabolomic profiles enabled researchers to distinguish between benign prostate tissue, clinically localized prostate cancer, and metastatic disease. Sixty metabolites were identified in localized and/or metastatic prostate tumors that were not present in benign prostate tissue. Ultimately, six metabolites, including sarcosine, were found to be significantly elevated during progression from benign tissue to localized cancer to metastatic disease. Sarcosine was also detected in the urine of men with prostate cancer. Because this metabolite showed progressive elevation from benign tissue to localized prostate cancer to metastatic disease, it was selected for further study.
To investigate the role of sarcosine in prostate cancer progression, the researchers performed analyses of laboratory-grown cells. They found that sarcosine levels were higher in invasive prostate cancer cells than in benign prostate cells. Moreover, the addition of sarcosine to benign prostate cells caused them to become invasive. By manipulating levels of the enzymes that regulate sarcosine metabolism, the researchers found they were able to control the invasiveness of benign and malignant prostate cells.
"Components of the sarcosine pathway could serve as novel avenues for therapeutic intervention," said Arul M. Chinnaiyan, M.D., Ph.D., Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. "Our next step will be to confirm these findings in a greater number of specimens and to have our results validated by other laboratories."
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Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Yong L, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, and Chinnaiyan AM. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. February 12, 2009.
Doubts Raised Over US Study on Prostate Cancer Screening Test
The study behind controversial research findings from the US that found a common blood test for prostate cancer has no benefit in reducing deaths has been challenged by Australias and New Zealands peak body for urological surgeons. AUCKLAND, Mar. 24 /Medianet International-AsiaNet/ -- Having carefully reviewed the study into Prostate Specific Antigen (PSA) blood tests undertaken in the United States, the Urological Society of Australia and New Zealand believes that there were design flaws in the US study which invalidate the results. We are concerned that Australian men may be persuaded against having a potentially life-saving PSA blood test following media reports of this US study, said USANZ president, Dr David Malouf.
Dr Malouf, who has just returned from the 24th Annual European Association of Urology Congress in Stockholm, said two studies about the PSA test recently published in the New England Journal of Medicine, one from the US and the other from Europe, had shown very different results and that the conflicting research findings must now be clarified.
The PLCO study in the US involved 76,000 men and did not demonstrate a benefit from screening. USANZ believes there are fundamental flaws in the study design which make the results of this trial less valid. The follow up of patients enrolled in the study was not of adequate duration and in the non-screened or usual care arm of the study more than half of the men underwent PSA testing, thus contaminating the unscreened population Dr Malouf said.
By contrast, the ERSPC study in Europe, commencing in the 1990s and involving 162,000 men in 8 European countries, demonstrated that routine prostate cancer screening could cut death rates from the disease by 20%. The study of men aged between 55 and 69 who underwent screening for prostate cancer had a 20% reduction in the risk of dying from prostate cancer compared with men who were not screened. The trial authors estimated that 1400 men would need to be screened to save one life from prostate cancer. These numbers required to save one life are similar to the numbers in breast and colorectal cancer screening programs. While some commentators have argued that many indolent cancers are unnecessarily detected as part of a screening process, in practice many of these men can be reassured and simply monitored without active treatment in the medium and long term, Dr Malouf said.
Routine population based prostate cancer screening with the PSA blood test is not performed in Australia or New Zealand and is, at present, not advocated by USANZ.
The position of this professional body remains that patients should have access to PSA based testing if they wish, after discussion with their family doctors and/or specialists about the risks and benefits of such testing.
There is firm data that testing reduces the risk of being diagnosed with advanced disease, and that treating prostate cancers following diagnosis can lead to a reduced risk of dying from the disease compared to no treatment.
The findings of the ERSPC study demonstrates the importance of developing new tests to identify aggressive forms of prostate cancer and differentiate them from more slowly growing tumours. Such a test will enable clinicians to focus treatment on men whose cancers pose a threat to their health and avoid over-treatment of men with the more indolent forms of the disease, he said.
Media enquiries:
Edwina Gatenby
Phone: +61 2 9965 9300
Mobile: +61 402 130 254
(+61 402 130 254 if calling from NZ)
ASIA PULSE
Drug Shows Activity in Men with Advanced Prostate Cancer
NEW YORK, Apr 08, 2009 (ASCRIBE NEWS via COMTEX) -- A new multi-center study shows that an experimental drug lowers prostate specific antigen (PSA) levels - a marker for tumor growth - in men with advanced prostate cancer for whom traditional treatment options have failed. The study, led by researchers at Memorial Sloan-Kettering Cancer Center (MSKCC), is published today in Science Express, the online version of the journal Science. Most men with metastatic prostate cancer eventually build up resistance to the drugs that lower or block male hormones and develop a more aggressive form of the illness called castration-resistant prostate cancer (CRPC), or hormone-refractory disease. According to the study's findings, investigators studied two novel compounds, RD162 and MDV3100, and not only gained an understanding of their novel mechanism of action, but found that these agents showed activity in CRPC cells in culture and in mice. The study also reports on a Phase 1/2 trial of MDV3100 in 30 patients with advanced CRPC and found that 22 out of 30 men showed declining PSA levels, and 13 out of 30 men (43 percent) had PSA levels fall by more than half.
Several years ago, the senior author of the study, Charles Sawyers, MD, and his colleagues at the University of California, Los Angeles (UCLA), uncovered a potential reason why metastatic prostate cancer patients eventually relapse with CRPC. This insight was used to discover RD162 and MDV3100.
"It's gratifying to know that our hypotheses about why men develop resistance to currently available treatments are confirmed and, most importantly, that there are already patients who are benefiting from our research," said Dr. Sawyers, Chair of the Human Oncology and Pathogenesis Program at MSKCC and a Howard Hughes Medical Institute investigator.
Current treatments for men who have advanced prostate cancers inhibit the activity of male hormones that help drive tumor growth. Many of these drugs disrupt the androgen (male hormone) receptor, which helps regulate cell proliferation, but tumors eventually become resistant to the drugs by expressing higher levels of the receptor. Preclinical studies by Dr. Sawyers and others have demonstrated that CRPC cells have increased expression of the androgen receptor and that overexpression of this receptor may contribute to the progression of disease.
Based on this information, Dr. Sawyers initiated a collaboration with Michael Jung, PhD, Professor of Chemistry at UCLA, that led to the discovery of a number of nonsteroidal, small molecule antiandrogen compounds, including MDV3100, which has been shown to retain its anticancer activity, even when the receptor's expression is elevated.
"The discovery and initial development of this drug was a collaborative effort all done in the academic setting, without reliance on the engine of the pharmaceutical industry that typically drives drug development," said Dr. Sawyers. Dr. Jung's group synthesized the compounds, which Dr. Sawyers' team then evaluated using prostate cancer mouse models engineered to highly express the androgen receptor, mimic progression to castration-resistant disease, and reflect the biology of clinical drug resistance.
According to the new study, the team of researchers tested various compounds to block the androgen receptor in CRPC cells. They chose to further evaluate the drug RD162 and a closely related compound, MDV3100. According to their findings, both drugs inhibit the androgen receptor function by impairing the receptor's ability to enter a CRPC cell's nucleus (called nuclear translocation), blocking it from binding to the DNA of its target genes, and preventing the cell from growing. They found that both compounds worked well in cells in culture, shrank tumors in mice, maintained tumor shrinkage for months, and prevented the androgen receptor from activating additional genes later in the process, or "downstream." Other currently approved drugs cannot disable the receptor in such a way.
The biopharmaceutical company Medivation, Inc., licensed RD162 and MDV3100 from UCLA in 2006 and has already completed enrollment in the first human trial of oral MDV3100 - a Phase 1/2 clinical trial, which was led by investigators at MSKCC and conducted through the Prostate Cancer Clinical Trials Consortium. The Consortium is sponsored by the Department of Defense and the Prostate Cancer Foundation. The trial enrolled men with metastatic, castration-resistant prostate cancer who relapsed after treatment with conventional hormone therapy and demonstrated anti-prostate cancer effects beginning with the first patient treated with MDV3100 at the lowest dose. Further positive results from an additional 110 patients who received the drug at higher doses were recently reported at the ASCO Genitourinary Cancers Symposium in February 2009.
"The declines in PSA levels observed thus far and the general tolerability of this treatment are encouraging," said Howard Scher, MD, a study co-author and Chief of the Genitourinary Oncology Service at MSKCC. "I am looking forward to continuing the study of this drug, which has the potential to be a powerful tool in a limited arsenal of treatments against this deadly form of the disease." A Phase 3 trial is planned to begin later this year.
Researchers at MSKCC, UCLA, Oregon Health and Science University, University of Washington, Seattle, and Medivation, Inc., contributed to the research. Dr. Sawyers and several of the study's authors are co-inventors on patent applications covering RD162, MDV3100, and related compounds.
The study was supported in part by the Prostate Cancer Foundation, the National Cancer Institute, and a Prostate Cancer Research Program Clinical Consortium Award.
Promising Test for Dendreon’s Prostate Cancer Drug
April 15, 2009 By ANDREW POLLACK <http://topics.nytimes.com/top/reference/timestopics/people/p/andrew_pollack/index.html?inline=nyt-per> A prostate cancer <http://health.nytimes.com/health/guides/disease/prostate-cancer/overview.html?inline=nyt-classifier> drug developed by the Seattle biotechnology company Dendreon <http://topics.nytimes.com/top/news/business/companies/dendreon-corporation/index.html?inline=nyt-org> prolonged the lives of men in a decisive clinical trial, the company announced Tuesday morning.
The widely anticipated results could pave the way for the drug, called Provenge, to become the first so-called therapeutic cancer “vaccine” to win approval in the United States after numerous failures of such drugs. “This looks like a proof of concept that cancer vaccines can and do work,” said Jeffrey Schlom, an expert on the vaccines at the National Cancer Institute <http://topics.nytimes.com/top/reference/timestopics/organizations/n/national_cancer_institute/index.html?inline=nyt-org> . Such vaccines work by harnessing the patient’s own immune system to fight the cancer. But the success in the trial could revive complaints about the Food and Drug Administration <http://topics.nytimes.com/top/reference/timestopics/organizations/f/food_and_drug_administration/index.html?inline=nyt-org> , which two years declined to approve Provenge despite an endorsement by one of the agency’s advisory committees.
The F.D.A. instead said it wanted more proof that the drug worked and would await results from a trial that was then underway, whose results were announced Tuesday.
The F.D.A.’s decision two years ago ignited an outcry from some prostate cancer patients and from investors in Dendreon, who said the agency was being unreasonable and denying patients a treatment that might work. Tensions ran so high at one point that two prostate cancer specialists, who had urged the F.D.A. not to approve the drug, attended a major conference accompanied by bodyguards, saying they had been threatened.
“Since that delay we have lost a lot of good men,” Ted Girgus of Bellingham, Wash., who has advanced prostate cancer, said Tuesday, calling the F.D.A. decision “a punch in the stomach.” Mr. Girgus, 65, who also owns Dendreon stock, said patients like himself are “looking into the abyss.”
“We know what our prognosis is,” he said. “But we want a chance.”
Dendreon did not reveal the actual results of its trial, saying they would be presented at a urology meeting on April 28.
But Mitchell Gold, the company’s chief executive, told analysts on a conference call, “It was an unambiguous hit on the primary endpoint of overall survival.” He said the outcome met the goals the company and the F.D.A. had agreed upon and that the results were consistent with those seen in earlier trials of Provenge.
In an interview Dr. Gold said Provenge would have had to reduce the risk of death by 22 percent compared to a placebo to meet the F.D.A. requirements for statistical significance.
Dendreon’s stock soared on the news. The shares were up more than 130 percent for the day, closing at $16.99.
The stock, which closed Monday at $7.30, had nearly tripled from its 52-week low of $2.55 in early March on anticipation of positive results. But there were also many investors who shorted the stock, betting the drug would fail in the clinical trial.
The trial involved 512 patients whose cancer had spread beyond the prostate gland and who were no longer benefiting from therapies intended to deprive the tumors <http://health.nytimes.com/health/guides/disease/tumor/overview.html?inline=nyt-classifier> of testosterone <http://health.nytimes.com/health/guides/test/testosterone/overview.html?inline=nyt-classifier> .
Dr. Gold said there were about 100,000 men who get such a diagnosis each year. The only approved treatment for them now is the Sanofi-Aventis <http://topics.nytimes.com/top/news/business/companies/sanofi_aventis/index.html?inline=nyt-org> chemotherapy <http://topics.nytimes.com/top/news/health/diseasesconditionsandhealthtopics/chemotherapy/index.html?inline=nyt-classifier> drug Taxotere, which extended median survival by about 3 months in trials.
Mark Monane, an analyst at Needham & Company, said sales of Provenge might reach $500 million to $1 billion a year.
Therapeutic vaccines like Provenge do not aim to prevent the disease, as a childhood vaccine does. Rather they aim to train the body’s immune system to attack the cancer once the patient is already ill.
There is already an approved treatment for bladder cancer <http://health.nytimes.com/health/guides/disease/bladder-cancer/overview.html?inline=nyt-classifier> that stimulates the immune system in general, but not specifically to fight the cancer. The cervical cancer vaccine <http://topics.nytimes.com/top/news/health/diseasesconditionsandhealthtopics/cervicalcancervaccine/index.htm?inline=nyt-classifier> now in use, Gardasil, is a more traditional preventive vaccine that works because cervical cancer <http://health.nytimes.com/health/guides/disease/cervical-cancer/overview.html?inline=nyt-classifier> is caused by a virus.
Proponents say cancer vaccines, also known as immunotherapy, could be a more precise way to attack cancer than bombarding them with poisons, as is now down in chemotherapy.
But development of cancer vaccines has been a path marked by numerous failures until now. Indeed, another prostate cancer vaccine called GVAX, developed by Cell Genesys <http://topics.nytimes.com/top/news/business/companies/cell-genesys-inc/index.html?inline=nyt-org> , failed in late-stage clinical trials last year.
Provenge had become a symbol of the sometimes passionate debate between patients who want faster access to experimental drugs and those who believe society as a whole benefits from greater proof that drugs work.
In an earlier trial, men who received Provenge lived a median of 25.9 months, compared with 21.4 months for those who received a placebo. At the end of three years, 34 percent of the men who got Provenge were alive, compared to only 11 percent for those who received a placebo.
Based on those results, an advisory panel to the F.D.A., meeting in March 2007, voted 13 to 4 that there was “substantial evidence” that the drug worked, and 17-0 that the drug was safe.
Still, some members of the committee said the evidence was somewhat weak because that trial involved only 127 men. And it had been intended to measure something different — not whether Provenge prolonged life, but whether it delayed the worsening of cancer. And the drug failed to do that by a statistically significant measure.
Two months later, the F.D.A. declined to approve Provenge, saying that more data were needed.
Protestors rallied outside an F.D.A. office in Rockville, Md., in September 2007. They took out ads in newspapers and on buses in the Washington area, including one that said “The FDA: killing hope, shortening lives.”
A group called Care to Live sued the F.D.A. to try to reverse the decision. But the courts essentially threw out the lawsuit, saying the F.D.A. had not made a final decision that could be challenged.
Harsh criticism was also directed against two prostate cancer specialists who had voted against Provenge on the advisory committee and later wrote letters to the F.D.A. urging that the drug not be approved. The two doctors, Howard I. Scher of Memorial Sloan-Kettering Cancer Center <http://topics.nytimes.com/top/reference/timestopics/organizations/m/memorial_sloankettering_cancer_center/index.html?inline=nyt-org> and Maha Hussain of the University of Michigan <http://topics.nytimes.com/top/reference/timestopics/organizations/u/university_of_michigan/index.html?inline=nyt-org> , were accompanied by bodyguards when they attended the nation’s largest cancer medical meeting in 2007.
Still, many prostate cancer patient advocacy groups did not support all those tactics or the lawsuit.
“I think the stockholders were more angry than the prostate cancer community,” said Jim O’Hara, a prostate cancer survivor and help line facilitator for the Prostate Cancer Research Institute, a patient education group. “The majority of the community that I talk to wants to see something approved that has gone through legitimate tests.”
Since the F.D.A. declined to approve Provenge, prostate cancer drugs from Cell Genesys, Novacea <http://topics.nytimes.com/top/news/business/companies/novacea-inc/index.html?inline=nyt-org> and GPC Biotech have failed in clinical trials.
Patients treated with Provenge have some white blood cells removed. Dendreon mixes those white cells, which are part of the immune system, with a genetically engineered protein that is a combination of an immune system stimulator and a molecule found in prostate cancer cells but only rarely elsewhere in the body.
The cells are then infused back into the patient, where they are meant to stimulate the immune system to attack anything that looks like the telltale prostate cancer molecule.
The treatment requires three infusions spaced two weeks apart, rather than periodic infusions over the course of months, as is common with chemotherapy. Provenge’s side effects also appear to be milder than those of Taxotere, some doctors say.
“Compared to standard chemotherapy, it’s just a whole lot easier for patients,” said Dr. David Penson, associate professor of urology at the University of Southern California <http://topics.nytimes.com/top/reference/timestopics/organizations/u/university_of_southern_california/index.html?inline=nyt-org> . He was an investigator in the trial and was a consultant to Dendreon a few years ago.
Provenge Surpasses Prostate Cancer Survival Projections
I had the opportunity to be in Chicago at the annual meeting of the American Urological Association (AUA) for the presentation of the Dendreon corporation successful clinical trial results for the first ever prostate cancer vaccine - PROVENGE.
PROVENGE trial results surpassed the survival benefits agreed to by the FDA as necessary for it to be approved as an available treatment. Provenge enhances the patient's own immune system to fight prostate cancer. The first IMMUNOTHERAPY treatment of this type for any cancer; a landmark medical breakthrough.
PHEN has worked with and supported Dendreon over the past few years in the company's quest to gain approval for PPROVENGE. Dr. Mitchell Gold, Dendreon president, presented at PHEN's 2006 African American Prostate Cancer Disparity Summit on Capitol Hill, and he is committed to making certain that Provenge is available to the men who suffer disproportionately from prostate cancer.
Thomas A Farrington
PHEN President and Founder
My statement which was presented at the AUA press conference on PROVENGE, Tuesday, April 28th is below. Farrington Statement on Provenge at AUA Statement
Dendreon Provenge Data Release The official release on the Provenge clinical trials results. Provenge Data
FDA Approves Degalerix for Advanced Prostate Cancer
Degarelix prostate cancer drug makes testosterone levels fall dramatically and quickly3. December 2008 22:10
More than 95 per cent of men who took degarelix for prostate cancer saw their testosterone levels fall dramatically as early as three days after they started treatment, according to a paper in the December issue of BJU International.
They also experienced much greater falls in their prostate-specific antigen (PSA) levels at 14 and 28 days than men taking leuprolide.
Researchers from Canada, the USA, France, Denmark and the Netherlands studied 610 men as part of the Phase Three trial, randomly assigning them to one of three study groups.
"Androgen deprivation hormone therapy is an effective response to prostate cancer, but the drugs that are most widely used cause an initial rise in testosterone - the hormone we are trying to reduce - when the patient first takes them" explains lead author Dr Laurence Klotz from the Division of Urology at the University of Toronto, Canada.
"We prefer to avoid this biochemical surge as it can stimulate the prostate cancer cells and exacerbate a number of clinical symptoms, such as spinal cord compression and bone pain. It could also result in more rapid growth of microscopic disease that is present in the patient but is too small to be detected.
"Degarelix is a new gonadotrophin-releasing hormone (GnRH) antagonist. It works by binding to, and blocking, the GnRH receptors in the pituitary gland, reducing the amount of LH and FSH hormones that are released. This leads directly to a rapid fall in testosterone."
Group one (207 patients) received an injection of 240mg of degarelix in month one, followed by a maintenance dose of 80mg every month for eleven months and group two (202 patients) received 240mg of degarelix in month one followed by a maintenance dose of 160mg for eleven months.
The third group (201 patients) received a monthly 7.5mg dose of leuprolide, which is a GnRH agonist.
At the start of the trial the study participants had a median testosterone level of 3.93 ng/mL. The aim was to reduce this to 0.5ng/mL or less at all monthly measurements from day 28 to day 364.
Eight out of ten study participants completed the trial (504 patients) between February 2006 and October 2007, with similar drop-out and exclusion rates in all three groups.
The key findings were impressive:
- Three days after starting their treatment regimes, 96.1 per cent of the patients on 240/80mg degarelix and 95.5 per cent of the patients on 240/160mg degarelix had achieved a testosterone level of 0.5ng/mL or less. In contrast, median testosterone levels in the leuprolide group had increased by 65 per cent by day three, but had reduced by day 28.
- At the end of the study period, 98.3 per cent of the 240/160mg degarelix group and 97.2 per cent of the 240/80mg degarelix group had achieved a testosterone level of 0.5ng/mL or less. The figure for the leuprolide group was 96.4 per cent.
- PSA levels fell much faster in the degarelix groups when measured at 14 and 28 days - by 64 per cent and 85 per cent in the degarelix 240/80mg group, 65 per cent and 83 per cent in the 240/160mg degarelix group and 18 per cent and 68 per cent in the leuprolide group.
The hormonal side-effects experienced by the three treatment groups were similar to previously reported effects for androgen deprivation hormone therapy.
Patients receiving degarelix were much more likely to experience injection-site reactions than those receiving leuprolide (40 per cent compared to one per cent).
However degarelix patients suffered fewer urinary tract infections than those in the leuprolide group (three per cent versus nine per cent) together with fewer joint pains and chills (four per cent versus nine per cent).
"More than 2,000 patients have now taken part in clinical trials for degarelix and there have been no signs of immediate or late-onset systemic allergic reactions, in contrast to other reported trials of other GnRH antagonists" points out Dr Klotz.
"The aim of the study was to show that degarelix was not inferior to leuprolide when it came to maintaining low testosterone levels over a one-year treatment period. We have conclusively shown that this is the case.
"However, we have also demonstrated that degarelix - which is an antagonist - offers an advantage, in that it reduces testosterone and PSA levels very quickly. It doesn't cause the initial surge of testosterone seen with agonist drugs like leuprolide - the other drug featured in this study.
"This is relevant as biochemical surges in testosterone can stimulate the prostate cancer cells and cause unpleasant side effects for patients. They may also require further drug therapy to counteract the effects of agonist drugs like leuprolide."
Robotic Prostate Surgery
New robotic prostate surgery not necessarily better By Julie Steenhuysen Tue Oct 13, 6:41 pm ET
CHICAGO (Reuters) – Men who have less invasive prostate cancer surgery -- often done robotically -- are more likely to be incontinent and have erectile dysfunction than men who have conventional open surgery, U.S. researchers said on Tuesday.
Many men, especially those who are wealthy and highly educated, favor minimally invasive surgery because they assume the high-tech approach will yield better results, but the evidence on that is mixed, the team reported in the Journal of the American Medical Association.
"We found men undergoing minimally invasive versus open surgery were more likely to have a diagnosis of incontinence and erectile dysfunction," Dr. Jim Hu of Brigham and Women's Hospital in Boston said in a telephone briefing. Hu said use of minimally invasive surgery has taken off since the introduction and heavy marketing of robot-assisted surgery, such as the da Vinci system made by Intuitive Surgical Inc.
The system consists of robotic arms, controlled from a console, that allow surgeons to perform less invasive surgeries. Hospitals advertise the systems as being able to reduce trauma, blood loss, risk of infection, scarring and often pain.
Hu said so far, there have been few studies that compare minimally invasive surgery with open surgery.
To do that, he and colleagues used billing data from the Medicare insurance program for the elderly on procedures done from 2003 to 2007. During that time, use of minimally invasive surgery for prostate cancer increased fivefold.
While both approaches fared equally well as a cancer treatment, they found that men who got the minimally invasive approach had shorter hospital stays, were less likely to need blood transfusions, and had fewer breathing problems after surgery than those who got conventional surgery.
But they were also more likely to have complications involving the genital and urinary organs, and they were more often diagnosed as having incontinence and erectile dysfunction than men who got open surgery.
The researchers also noted that fewer black and Hispanic men had the minimally invasive surgery, while Asians were much more likely to get the high-tech surgery.
CHOICE RELATED TO EDUCATION, WEALTH
Men who got the minimally invasive surgery were far more likely to live in areas with at least 90 percent high school graduation rates and median income of at least $60,000.
The fact that highly educated, wealthier men favored the higher technology alternative "despite insufficient data demonstrating superiority" may reflect a healthcare system "enamored with new technology" that increases health costs without offering clear benefits, Hu and colleagues wrote.
Ryan Rhodes, marketing director for Intuitive Surgical, disputed the findings.
"There have been over 800 papers published in peer reviewed journals talking about the outcomes of radical prostatectomy. The majority of these were favorable," Rhodes said.
He said the current study used Medicare billing data, which does not distinguish between robot-assisted and other types of minimally invasive prostate surgery.
"Looking at the data, you cannot accurately assess which patients were operated on robotically," he said.
Dr. Herbert Lepor of New York University's Langone Medical Center analyzed several studies on robotic-assisted prostate surgery in a paper published this year in Reviews in Urology. He said so far the evidence does not suggest the robotic procedure is superior to open surgery.
Lepor, who was not involved in the study, estimates that about 80 percent of minimally invasive prostate cancer surgery is done robotically. "What drives this is the industry creating the need," he said.
"We've increased the cost of care with the robot," he said. "Now what we are learning is continence and potency seem to be inferior."
Coffee May Reduce Risk of Deadly Prostate Cancer (Update1)
By Simeon Bennett
Dec. 8 (Bloomberg) -- Drinking coffee may lower the risk of developing the deadliest form of prostate cancer, according to a Harvard Medical School study.
In research involving 50,000 men over 20 years, scientists led by Kathryn Wilson at Harvard’s Channing Laboratory found that the 5 percent of men who drank 6 or more cups a day had a 60 percent lower risk of developing the advanced form of the disease than those who didn’t consume any. The risk was about 20 percent lower for the men who drank 1 to 3 cups a day, and 25 percent lower for those consuming 4 or 5 cups.
The study is the first to associate coffee with prostate cancer, contradicting previous research that’s found no link. The difference may be because Wilson and colleagues looked for the first time at the link between coffee and different stages of the disease, instead of grouping them all together. More research is needed to confirm the findings, she said.
“People shouldn’t start changing their coffee consumption based on one study,” Wilson said in a phone interview on Dec. 5. “It could be chance, and we really need to see whether it pans out in other studies.”
Prostate cancer struck almost 200,000 men in the U.S. this year and killed more than 27,000, making it the second-deadliest malignancy among American men after lung cancer, according to the American Cancer Society. About 54 percent of U.S. adults drink coffee, according to the New York-based National Coffee Association.
Multiple Components
The researchers aren’t sure which of the many components of coffee is responsible for the effect, though it probably isn’t caffeine because the same association was seen for decaffeinated coffee, Wilson said. The link wasn’t seen in patients with an earlier stage of prostate cancer, she said.
Coffee lowers the risk of Type 2 diabetes by increasing the body’s ability to use insulin to convert blood sugar to energy, previous research has shown.
Higher insulin levels have also been associated with an increased risk of prostate cancer, suggesting the hormone may be the link between coffee and the disease, Wilson said.
The data were presented at an American Association for Cancer Research conference in Houston.
To contact the reporter on this story: Simeon Bennett in Singapore at sbennett9@bloomberg.net
Last Updated: December 8, 2009 01:21 EST
Surgery offers Long-Term Survival for Early-Stage Prostate Cancer Patients
ROCHESTER, Minn. — In the largest, most modern, single-institution study of its kind, Mayo Clinic urologists mined a long-term data registry for survival rates of patients who underwent radical prostatectomy for localized prostate cancer. The findings are being presented at the North Central Section of the American Urological Association's 84th Annual Meeting in Chicago. A radical prostatectomy is an operation to remove the prostate gland and some of the tissue around it. In this study, Mayo Clinic researchers discovered very high survival rates for the 10,332 men who had the procedure between 1987 and 2004. This time period was chosen because it reflects the modern era of prostate cancer detection with the introduction of the prostate-specific antigen (PSA) test.
The researchers looked at overall survival, cancer-specific survival, progression-free survival and local recurrence at five to 20 years. Only 3 percent of patients died of prostate cancer. Five percent showed evidence of cancer spread to other organs and 6 percent had a local recurrence of cancer. Study participants had a median survival time of 19 years, and 8,000 are living to date. The mean and median follow-up period was 11 years.
"These are excellent survival rates," says R. Jeffrey Karnes, M.D., a Mayo Clinic urologist and senior author on the study. "They show that radical prostatectomy is a benchmark for treatment of men with prostate cancer that has not spread."
Radical prostatectomy was the primary treatment for the men. Studies done before the introduction of the PSA test showed less favorable survival results. Prior to the PSA test, prostate cancer was detected by symptoms or by a digital rectal exam (DRE), both of which were less likely to detect cancer before it had spread beyond the prostate.
"The findings are a testament to the individuals who have helped manage the database over the years, the many Mayo surgeons who performed the procedures with a similar approach and, ultimately, the patients," says Dr. Karnes.
Collaborators include Eric Bergstralh, Xin Wang, Ph.D., and Rui Qin, Ph.D., of Mayo Clinic. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. For information about research and education, visit www.mayo.edu.MayoClinic.com (www.mayoclinic.com) is available as a resource for your health stories.
High Dietary Fat, Cholesterol Linked to Increased Risk of Breast Cancer and Prostate Cancer
ScienceDaily (Jan. 7, 2011) — Elevated fat and cholesterol levels found in a typical American-style diet play an important role in the growth and spread of breast cancer, say researchers at the Kimmel Cancer Center at Jefferson. The study, published in the January issue of The American Journal of Pathology, examines the role of fat and cholesterol in breast cancer development using a mouse model. The results show that mice fed a Western diet and predisposed to develop mammary tumors, can develop larger tumors that are faster growing and metastasize more easily, compared to animals eating a control diet.
The research team led by cancer biologist Philippe G. Frank, Ph.D., Assistant Professor in the Department of Stem Cell Biology and Regenerative Medicine at Thomas Jefferson University, was interested in learning about the link between diet and breast cancer. The incidence rate of this cancer is five times higher in Western countries than in other developed countries. Moreover, studies have shown an increase in breast cancer incidence in immigrant populations that relocate from a region with low incidence. "These facts suggest strong environmental influence on breast cancer development," says Dr. Frank.
Dietary fat and cholesterol have been shown to be important risk factors in the development and progression of a number of tumor types, but diet-based studies in humans have reached contradictory conclusions. This has led Dr. Frank to turn to animal models of human cancer to examine links between cholesterol, diet, and cancer.
The research team turned to the PyMT mouse model to determine the role of dietary fat and cholesterol in tumor development. This mouse model is believed to closely parallel the pathogenesis of human breast cancer. PyMT mice were placed on a diet that contained 21.2 percent fat and 0.2 percent cholesterol, reflective of a typical Western diet. A control group of PyMT mice was fed a normal chow that had only 4.5 percent fat and negligible amounts of cholesterol.
The researchers found that tumors began to develop quickly in mice fed the fat/cholesterol-enriched chow. In this group, the number of tumors was almost doubled, and they were 50 percent larger than those observed in mice that ate a normal diet. "The consumption of a Western diet resulted in accelerated tumor onset and increased tumor incidences, multiplicity, and burden, suggesting an important role for dietary cholesterol in tumor formation," Dr. Frank says. There was also a trend towards an increased number of lung metastasis in mice fed the fatty diet, he adds.
To confirm the aggressive nature of the cancer in animals fed a cholesterol-rich diet, the researchers examined the levels of several biomarkers of tumor progression and found a signature of a more advanced cancer stage, compared to tumors that developed in the control group.
The researchers also showed that plasma cholesterol levels in experimental mice that developed tumors were significantly reduced compared to a group of "wild-type" mice -- animals with no predisposition to develop tumors -- that was also fed a cholesterol-rich diet. "This suggests that tumor formation was responsible for the reduction in blood cholesterol levels observed in our animals," indicates Dr. Frank.
Dr. Frank explains the use of cholesterol in breast tumors this way: "In a neighborhood, if you want to build more houses, you need more bricks. In tumors, cholesterol provides the bricks that are the foundation for further growth, and this cholesterol comes from the blood. A drop in blood cholesterol may signify that some tumors are growing as cholesterol provides support for breast cancer growth."
"These data provide new evidence for an increase in cholesterol utilization by breast tumors and thus provides many new avenues for prevention, screening, and treatment," indicates Dr. Frank. These findings suggest that use of cholesterol-lowering drugs, such as statins, may both protect against breast cancer as well as treat patients carrying tumors. Since researchers also found that blood cholesterol levels dropped significantly as tumors began to develop, the study indicates measuring blood cholesterol levels may also be an effective method of screening cancer development.
This research team also discovered the same association between cholesterol and growth of prostate cancer in mice in a study published in the December issue of The American Journal of Pathology. The results of these two new studies indicate, according to Dr. Frank that, "Cholesterol does indeed seem to be an important factor in the regulation of tumor formation in several cancer types."