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Kanker Prostat

Dimulai oleh syx, Februari 18, 2010, 07:42:18 AM

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syx

From Medscape Medical News
Finasteride Reduces Prostate Cancer Risk, but Which Men Should Receive It?

February 11, 2010 — Finasteride (Proscar) reduced the risk for prostate cancer by nearly 25% in the large Prostate Cancer Prevention Trial (PCPT), which was conducted in men 55 years and older.

But this finding begs the question of who to recommend the drug to, say the authors of a new analysis published online February 1 in the Journal of Clinical Oncology.

Despite the encouraging findings of the PCPT, the use of finasteride to prevent cancer in the community remains low and is not widely used, explained lead author Andrew Vickers, PhD, associate attending research methodologist at Memorial Sloan-Kettering Cancer Center in New York City.

"This suggests that, for the average man, the benefits of finasteride, in terms of reduced risk, do not outweigh the harms," he told Medscape Oncology.

The analysis conducted by Dr. Vickers and colleagues found that risk-group stratification for treatment with finasteride is "unlikely to be beneficial for preventing all prostate cancers detectable at biopsy." But if cancers found as a result of routine clinical care are used as an end point, then the optimal strategy would be to treat a subgroup of men at high risk rather than the whole at-risk population, they write.

The interpretation of these results, in relation to whether finasteride should be used as chemopreventive therapy for all men or for only for those at higher risk, depends on the relative clinical significance of cancers found during the end-of-study biopsy, the authors explain.

Basically, clinicians should recommend finasteride to all men if they want to reduce the risk for any biopsy-detectable prostate cancer.

However, "clinicians who believe that it is unnecessary to prevent all cancers, but that preventing those readily detectable by screening is desirable, would be best off recommending finasteride only to a high-risk subgroup," they write.

Balancing Benefit and Harms

The primary adverse effect associated with finasteride is decreased sexual function, the authors explain. Even though this effect is generally mild, the reduction in libido can be experienced immediately. Conversely, men at higher risk have a greater potential benefit from finasteride. Therefore, note the authors, a strategy that focuses on high-risk men might tip the balance between the benefits and harms of finasteride in favor of treatment.

"Along with many other groups, we have shown that the risk of getting prostate cancer over the course of next 5 to 10 years is strongly dependent on your PSA [prostate-specific antigen] level," said Dr. Vickers. "If you have a high PSA level, you are naturally a candidate for immediate biopsy. But even among those who are not candidates for biopsy, higher PSA means higher risk."

As an example, few clinicians would consider biopsying a man with a PSA of 0.8 ng/mL or one with a PSA of 1.6 ng/mL. "However, the man with the PSA of 1.6 ng/mL has a much higher risk of being diagnosed with prostate cancer over the next 5 to 10 years," he said.

Dr. Vickers explained that, in this study, he and his colleagues demonstrate that not only is the risk higher with increasing PSA, but the effects of finasteride are larger for men with a higher PSA level. "For example, the risk of cancer goes down by about 1% for the man with a PSA of 0.8 ng/mL but nearly 3% for the man with a PSA of 1.6 ng/mL," he said.

"We go on to show, using decision analysis, that it makes the most sense to offer finasteride not to all men at risk for prostate cancer, but only to men with a PSA above 1.3 ng/mL or those with a PSA above 2 ng/mL," Dr. Vickers continued. "Whether you choose 2 or 1.3 ng/mL for your cut-point depends on your views about the relative benefits and harms of taking finasteride."

A patient who is anxious about prostate cancer might be advised to take finasteride for a PSA of 1.5 ng/mL, for example, whereas one who prefers not to take drugs unless needed might be advised to take finasteride if his PSA is above 2 ng/mL, he added.

Study Details

In the current study, Dr. Vickers and colleagues used raw data from the PCPT to model chemopreventive treatment strategies to determine whether PSA levels can identify a high-risk subgroup in which the benefits of finasteride treatment outweigh the potential harm.

For their analysis, they weighed the benefits and harms for each strategy using number-needed-to-treat (NNT) thresholds, or the maximum number of patients that a clinician would need to treat with finasteride to prevent 1 cancer.

Their analysis consisted of 9058 men, 1957 of whom were diagnosed with prostate cancer during the 7-year study period: 798 (18.3%) men were in the finasteride group and 1159 (24.7%) were in the placebo group. Demographic characteristics such as baseline PSA, age, race, and family history were similar in both groups.

The overall risk of being diagnosed with cancer was 21.6% and, in both groups, approximately half of all cancers were detected by a biopsy that followed an elevated PSA level and/or an abnormal digital rectal exam result.

The authors observed that PSA levels were significantly associated with the outcome of all cancers and for-cause cancers (P < .001 for both). The data were divided into approximate quintiles according to baseline PSA, and then the clinical net benefit of treating by each of these cut points was determined.

They note that for the outcome of detecting all cancers, it is difficult to justify stratifying the population into risk groups and treating only men who are at high risk. For an extremely conservative clinician, such as one who would treat no more than 10 men to prevent 1 cancer, the highest clinical net benefit would be obtained from treating only the highest quintile of the population. But for the other NNT threshold, they write, the optimal strategy would be to treat either all men at risk or all but the lowest-risk quintile.

If only cancers that are detected by a for-cause biopsy are considered, "there is a clear case for recommending finasteride to some, but not all, men," they write. The optimal strategy, across all NNT thresholds, is to treat either 20% or 40% of those with the highest PSA levels. If only men with a PSA of 1.3 ng/mL or greater are given finasteride, the treatment rate would be reduced by 62%, with only a small increase in the event rate (from 9.6% to 9.9%).

Restricting the use of finasteride to men with a PSA of greater than 2 ng/mL would reduce the treatment rate by 83% and result in a cancer rate only 1.1% higher than treating all men, they note.

The study was supported in part by funds from David H. Koch provided through the Prostate Cancer Foundation, the Sidney Kimmel Center for Prostate and Urologic Cancers, and a SPORE grant from the National Cancer Institute. Dr. Vickers and coauthor Hans Lilja, MD, PhD, also from Memorial Sloan-Kettering Cancer Center, report receiving honoraria from GlaxoSmithKline. Hans Lilja also reports owning stock in Arctic Partners Oy.

J Clin Oncol. Published online February 1, 2010.

Huriah M Putra

Finasteride itu obat untuk BPH toh..? Menghambat pembentukan dihidrotestosteron...
Berarti secara tak langsung kita bisa menyimpulkan kalau kanker prostat salah satu resikonya adalah karna kadar DHT yang tinggi...?
[move]OOT OOT OOT..!!![/move]

Astrawinata G

lho, emang gitu kan teorinya?prostat semakin besar kalo ditempeli DHT...
Best Regards,


Astrawinata G

Huriah M Putra

Semakin besar secara jinak, bukan ganas...
Makanya kalo DHT tinggi, BPH yang terjadi.. (Benign)
[move]OOT OOT OOT..!!![/move]

Astrawinata G

BPH beresiko ke maligna ga ya? ???
Best Regards,


Astrawinata G

Huriah M Putra

[move]OOT OOT OOT..!!![/move]

Astrawinata G

Best Regards,


Astrawinata G

Huriah M Putra

Gak... setahu saya. Kok hilang setahu sayanya diatas..?
[move]OOT OOT OOT..!!![/move]

syx

FDA Approves Provenge, the First Immunotherapy for Metastatic Prostate Cancer

April 29, 2010 — In a widely anticipated announcement, the US Food and Drug Administration (FDA) has approved an immunotherapy, sipuleucel-T (Provenge, Dendreon), for the treatment of asymptomatic or minimally symptomatic metastatic, castration-resistant prostate cancer (mCRPC).

Often referred to as a vaccine, sipuleucel-T is an autologous active cellular immunotherapy, meaning that it is made from the patient's own white blood cells and stimulates a patient's immune system to respond against the cancer. The treatment needs to be manufactured individually for each patient.

"The availability of [sipuleucel-T] provides a new treatment option for men with advanced prostate cancer who currently have limited effective therapies available," said Karen Midthun, MD, acting director of the FDA's Center for Biologics Evaluation and Research, in a press statement.

Sipuleucel-T becomes the first product approved by the FDA in a new therapeutic class known as active cellular immunotherapies, according to Dendreon press materials.

To be approved by the FDA, investigators had to show that sipuleucel-T would extend survival in men with mCRPC.

In the pivotal phase 3 study, with a median follow-up of 36.5 months, men treated with sipuleucel-T (n = 341) had a median survival of 25.8 months, compared with men treated with placebo (n = 171), who had a median survival of 21.7 months

Thus, with the new therapy, there was a 4.1-month median survival advantage and a 24.1% reduction in the risk for death (hazard ratio, 0.759; P = .017), compared with placebo.

These latest data from the pivotal trial, known as IMPACT (Immunotherapy for Prostate Adenocarcinoma Treatment), were presented at the American Society of Clinical Oncology 2010 Genitourinary Cancers Symposium in March.

Last year, after a presentation of very similar survival data on sipuleucel-T at the 2009 American Urological Association (AUA) annual meeting, one of the study investigators hailed the survival benefit.

This 4-month extension in survival is very, very significant.

"This 4-month extension in survival is very, very significant," said David F. Penson, MD, MPH, at the AUA meeting. Dr. Penson is a professor of medicine at the University of Southern California Los Angeles.

"These patients have a life expectancy of about 2 years, so giving them 4 more months is pretty important. It gives them about 20% more life. And [sipuleucel-T] does it with minimal adverse events. So there is improved survival with good quality of life," he added.

According to the FDA press release, the most common adverse reactions reported with the new product are chills, fatigue, fever, back pain, nausea, joint ache, and headache. The majority of adverse reactions were mild or moderate. Serious adverse reactions, which were reported in approximately one quarter of the patients receiving sipuleucel-T, included some acute infusion reactions and stroke.

Cerebrovascular events, including hemorrhagic and ischemic strokes, were observed in 3.5% of patients in the sipuleucel-T group, compared with 2.6% of patients in the placebo control group

The approval of sipuleucel-T has been a long time coming.

In 2007, the FDA deferred approval of sipuleucel-T until a statistically significant improvement in survival could be shown.

The study investigators revealed such an improvement at the 2009 AUA annual meeting.

We don't have anything for patients with hormone-refractory disease.

At the time, AUA spokesman J. Brantley Thrasher, MD, chair of the Department of Urology at the University of Kansas Medical Center in Kansas City, said that "this will cause a big splash."

"We don't have anything for patients with hormone-refractory disease, which is very aggressive. . . . Improved survival with T cell immunotherapy is really very significant," he said.

syx

Finger Length a Clue to Prostate Cancer Risk

December 2, 2010 — Men whose index finger is longer than their ring finger are at a lower risk of prostate cancer than those with a finger pattern the other way round, according to a new study in the British Journal of Cancer.

The relative length of the first and third fingers is set before birth, and it is thought to relate to the levels of sex hormones the baby is exposed to in the womb. Babies exposed to less of the male sex hormone testosterone are more likely to have longer index fingers.

Finger Length and Prostate Cancer

Over a 15-year period, researchers from The University of Warwick and The Institute of Cancer Research (ICR) collected data on finger length in 1,524 patients with prostate cancer as well as 3,044 healthy people. Men were shown pictures of hands with different finger lengths and asked to identify the one most like their own right hand.

The most common finger length pattern, seen in more than half the men in the study, was a shorter index than ring finger. Men whose index and ring fingers were the same length (about 19%) had a similar prostate cancer risk to those with a shorter index than ring finger. However, men whose index fingers were longer than their ring finger were 33% less likely to have prostate cancer.

Risk reduction was even greater in men aged under 60, say the researchers, who found that this younger group were 87% less likely to be in the prostate cancer group.

Testosterone Exposure

The researchers believe that being exposed to less testosterone before birth helps protect against prostate cancer later in life. The phenomenon is thought to occur because the genes HOXA and HOXD control both finger length and development of sex organs.

"Our results show that relative finger length could be used as a simple test for prostate cancer risk, particularly in men aged under 60," says joint senior author Professor Ros Eeles from the ICR and The Royal Marsden NHS Foundation Trust. "This exciting finding means that finger pattern could potentially be used to select at-risk men for ongoing screening, perhaps in combination with other factors such as family history or genetic testing."

The study was funded by Prostate Cancer Research Foundation and Cancer Research UK.

Diagnosing Prostate Cancer

Helen Rippon, head of research at The Prostate Cancer Charity in the U.K., says in an emailed statement: "Diagnosis of prostate cancer is not a simple affair and the best blood test we have, known as a PSA test, tells us only that something might be wrong with the prostate, not whether it is cancerous or not. Anything that adds to our knowledge about whether a man is likely to develop prostate cancer or not is to be welcomed, especially when it is something as easy as looking at the length of his fingers.

"This research also adds to the growing body of evidence that the balance of hormones we are exposed to before birth influences our health for the rest of our lives."

Rippon says men who check their hands and find they have a shorter index finger should not be unduly concerned. "They share this trait with more than half of all men and it does not mean they will definitely develop prostate cancer in later life," she says.

SOURCES:

News release, University of Warwick.

Eeles, R. British Journal of Cancer.

Helen Rippon, The Prostate Cancer Charity.