FDA: Include warnings on risk for class of prostate cancer drugs

The U.S. Food and Drug Administration today asked manufacturers to add new warnings to labeling of gonadotropin-releasing hormone (GnRH) agonists, a class of drugs primarily used to treat men with prostate cancer.

The warnings would alert patients and their health care professionals to the potential risk of heart disease and diabetes in men treated with these medications.

In May, the FDA said that a preliminary and ongoing analysis found that patients receiving GnRH agonists were at a small increased risk for diabetes, heart attack, stroke, and sudden death. The new labels will include updates in the Warnings and Precautions section about these potential risks.

Prostate cancer is the second most common type of cancer among men in the United States, behind skin cancer, and usually occurs in older men. This year an estimated 217,730 new cases of prostate cancer will be diagnosed and about 32,050 men will die from the disease, according to the Centers for Disease Control National Center for Health Statistics and the National Cancer Institute.

GnRH agonists are drugs that suppress the production of testosterone, a hormone involved in the growth of prostate cancer. This type of treatment is called androgen deprivation therapy, or ADT. Suppressing testosterone has been shown to shrink or slow the growth of prostate cancer.

GnRH agnoists are marketed under the brand names: Eligard, Lupron, Synarel, Trelstar, Vantas, Viadur, and Zoladex. Several generic products are available.

U.S. Food and Drug Administration

Popular prostate cancer treatment associated with bone decay

Using novel technology allowing "virtual bone biopsies" researchers have found that a common treatment for prostate cancer called androgen deprivation therapy (ADT) is associated with structural decay of cortical and trabecular bone. The study has been accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).

Prostate cancer is the second most common cancer in men worldwide and estimates suggest there are currently 600,000 men in the United States with the condition who are being treated with ADT. Prostate cancer relies upon male hormones for its growth and ADT is a common treatment because it suppresses or blocks the production or action of male sex hormones. This is the first study to examine changes in bone structure during ADT.

"We used a new technology that allows us to assess bone microarchitecture and we found ADT is associated with structural decay of corticol (hard outer shell) and trabecular (spongy inner mesh) bone," said Emma Hamilton, MBBS and Mathis Grossmann, MD, PhD, of the University of Melbourne in Australia and lead authors of the study. "This technology may be a useful test in predicting fractures in patients, but further research is needed in identifying individuals at greatest fracture risk as well as optimal therapeutic strategies."

In this study, researchers conducted a 12 month prospective observational study of 26 men with prostate cancer who began ADT. At several points during the study, measurements were taken for sex steroid levels, bone turnover markers and bone mineral density. Furthermore, researchers used three-dimensional high resolution peripheral quantitative computed tomography (HR-pQCT) to assess bone microarchitecture. This technology allows researchers to take virtual bone biopsies, according to Grossmann.

"Sex steroid deficiency induced by ADT for prostate cancer results in microarchitectural decay," said Grossmann. "Bone fragility in these men may be more closely linked to testosterone than estradiol deficiency."

The Endocrine Society

Prostate cancer patients on hormone therapy at increased risk for various heart diseases

New research has found that hormone therapy used to treat men with advanced prostate cancer is associated with an increased chance of developing various heart problems. Some choices of therapy appear, however, to be less risky than others.

Researchers told Europe's biggest cancer congress, ECCO 15 – ESMO 34], in Berlin today (Tuesday 22 September) that the findings of their study, the largest and most comprehensive to date on the issue, indicate that doctors need to start considering heart-related side effects when they prescribe endocrine therapy for prostate cancer and might want to refer patients to a cardiologist before starting treatment.

A few smaller studies have indicated that some types of hormone therapy increase the risk of coronary heart disease and heart attacks in prostate cancer patients, but others have found no increased risk. This is the first large study to investigate how the broader range of hormone therapies affect a wider range of heart problems and provides for the first time a detailed picture of the impact of each sort of hormone therapy on individual types of heart trouble.

"If we have observed a causative effect, then for all hormone therapies put together, we estimate that compared with what's normal in the general population, about 10 extra ischaemic heart disease events a year will appear for every 1,000 prostate cancer patients treated with such drugs," said the study's leader, Ms Mieke Van Hemelrijck, a cancer epidemiologist at King's College in London. "However, not all types of therapy were associated with the risk of heart problems to the same degree. We found that drugs which block testosterone from binding to the prostate cells were associated with the least heart risk, while those that reduce the production of testosterone were associated with a higher risk. This may have implications for treatment choice."

Prostate cancer is diagnosed in more than 670,000 men each year worldwide, making it the second most common cancer among men worldwide, after lung cancer. Hormone therapy is a mainstay of treatment when the cancer is locally advanced and when it has spread to more distant parts of the body, but is increasingly being used in earlier stages of the disease. It involves either removing the testicles to eliminate the main source of testosterone production, injections of gonadotropin releasing hormone agonists to dramatically reduce the production of testosterone from the testicles or anti-androgen pills, which do not reduce the amount of testosterone produced but block it from attaching the prostate cells. Doctors sometimes use a combination of those approaches.

In the study, researchers analysed the link in 30,642 Swedish men with locally advanced or metastatic prostate cancer who had received hormone therapy as primary treatment for their disease between 1997 and 2006. The men were followed for an average of three years. The researchers calculated the risk of developing ischaemic heart disease, heart attacks, arrhythmia and heart failure requiring hospitalisation as well as the risk of dying from these heart diseases by comparing the rates among the cancer patients with what's normal in the general Swedish population. Most patients got one of the three hormone treatment choices, but 38% got a combination of the two types of drugs.

"We found that prostate cancer patients treated with hormone therapy had an elevated risk of developing all of the individual types of heart problems and that they were more likely than normal to die from those causes," Ms Van Hemelrijck said, adding that the problems started happening within a few months of initiating treatment.

Overall, prostate cancer patients treated with hormone therapy had a 24% increased risk of a non-fatal heart attack, a 19% increased risk of arrhythmia, a 31% increased risk of ischaemic heart disease and a 26% increased risk of heart failure. The risk of a fatal heart attack was increased by 28%, the risk of dying from heart disease by 21%, the risk of heart failure death was increased by 26% and the risk of fatal arrhythmia was increased by 5%.

"In a more detailed analysis by type of hormone therapy, the lowest increase in risk for ischaemic heart disease, heart attack and heart failure was seen in the group taking anti-androgen therapy, and we saw no increase in risk of death from heart disease in this group," Ms Van Hemelrijck said. "Patients on gonadotropin releasing hormone agonist therapy had the highest risk of these problems."

For instance, the increased heart failure risk for anti-androgens was 5%, compared with 34% for gonadotropin releasing hormone agonists and the increased ischaemic heart disease risk was 13% in the anti-androgen group, compared with 30% in the gonadotropin releasing hormone agonist therapy group.

"The finding that anti-androgens carry the least heart risk supports the view that circulating testosterone may protect the heart," she said.

The association with heart risk when the testicles were removed was close to that seen with the gonadotropin releasing hormone agonist therapy, Ms Van Hemelrijck added.

The increased risk of heart events requiring hospitalisation was less pronounced in patients who already had heart disease before hormone treatment, with a 17% risk increase for a new ischaemic heart disease event among those with a history of heart disease, compared with a 41% increase among men who didn't have any heart trouble before hormone treatment, for instance. Ms Van Hemelrijck said that could be because the men who already had heart disease were likely to be taking heart medications that protected them from further heart risk imposed by the endocrine treatment.

"We now need studies verifying the association and exploring plausible biological mechanisms. Then we would know how to best use these treatments according to a patient's history of various types of heart disease and whether it would be a good idea to give patients heart medicines to counteract these side effects," Ms Van Hemelrijck concluded.

ECCO-the European CanCer Organisation

UCLA study details quality of life for prostate cancer patients 4 years out from treatment

A long-term study by researchers at UCLA's Jonsson Comprehensive Cancer Center found that the three most common treatments for localized prostate cancer had significant impacts on patients' quality of life, a finding that could help guide doctors and patients in making treatment decisions.

The four-year study, which followed 475 men treated for early stage prostate cancer, also resulted in the development of "probability plots," gauges which can be used to predict when treatment side effects such as urinary incontinence, sexual dysfunction or bowel problems might return to normal, or whether the patient will ever fully recover. Such predictions could be used to determine whether further treatments or surgeries are needed to deal with adverse side effects, said Dr. John Gore, an urologist and the study's first author.

The study appears June 9 in the early online edition of the Journal of the National Cancer Institute.

"These probability plots are more helpful than the normal functional trajectory curves that are used," Gore said. "They allow people to point toward where the function level is currently and predict what it might be in the future. Is a patient's incontinence, for example, likely to get better? If not, the doctor and patients may agree to proceed with treatment options such as drugs or surgery."

The study is unique because it is not a cross-sectional review. Rather, researchers knew what a patient's baseline function was prior to treatment. That way, Gore said, they had a target to shoot for in judging recovery from side effects. The goal was to get the patient back to the function level experienced before treatment, if possible.

The researchers studied the quality of life in men who either underwent radical prostatectomy, implantation of radioactive seeds in their prostate gland or had external beam radiation therapy. The three treatment options rank about equally in survival outcomes for most men, so specific impacts on quality of life become paramount in making treatment decisions, said Dr. Mark Litwin, the study's senior author, a professor or urology and a researcher at UCLA's Jonsson Cancer Center.

"The good news is that the patients' overall mental and physical well-being were not profoundly affected by any of the three treatment choices," Litwin said. "That's good news for men with a diagnosis of prostate cancer hanging over their heads. In general, they'll be OK, no matter which of the three options they choose."

The study found that urinary incontinence was more common among patients who underwent prostatectomy than those who had seed implants, called brachytherapy, or external beam radiation. Sexual dysfunction was found in patients in all three treatment groups. Surgery patients were less likely to regain baseline sexual function than were patients who underwent external beam radiation. Bowel dysfunction and irritable bladder were more common after either form of radiation therapy than after prostatectomy.

Study patients were given comprehensive questionnaires to fill out before treatment to assess generic and prostate cancer-specific, health-related quality of life. Questionnaires were filled out again at one, two, four, eight, 12, 18, 24, 30, 36, 42 and 48 months after treatment to "capture maximal fluctuations in functional convalescence," the study states.

The most rapid change in the slope of patient recovery came very early after treatment, Gore said, either for better or worse. However, once more than two years had passed, the patient's recovery or decline had stabilized.

The study patients were diagnosed with the most common type of prostate cancer, low-risk, clinically localized disease. Many of the patients were older men and already were experiencing age-related functional issues such as erectile dysfunction, so each had individual baseline goals to achieve.

The study will allow oncologists to look at the patient, look at the characteristics of their cancer and determine what treatment will mostly likely help them to achieve their baseline health-related quality of life. For example, a patient with an existing irritable bladder condition should probably not receive external beam radiation because the treatment could exacerbate the underlying condition. A patient's acceptance of potential side effects also should be considered.

"Different men are bothered by different things, so it depends on what their baseline function is," Litwin said. "If a man is already impotent, for example, loss of sexual function won't be an issue in making a treatment decision."

University of California, Los Angeles

Microwave treatments for enlarged prostate cause blood pressure surges

Many men who receive microwave therapy for enlarged prostates experience significant surges in blood pressure that could raise their risk of a heart attack or stroke, according to new research findings published recently in Mayo Clinic Proceedings.

The Mayo Clinic-led study of 185 consecutive patients who received transurethral microwave therapy at four medical centers found that 42 percent experienced systolic blood pressure surges of more than 30 mm Hg, while 5 percent had surges of more than 70 mm Hg.

“Men who are candidates for this minimally invasive microwave therapy tend also to be at higher risk for cardiac events,” says Lance Mynderse, M.D., the Mayo Clinic urologist who authored the study. “Blood pressure surges of the magnitude identified in this study are troubling side effects of treatment that need to be monitored and managed.”

Benign prostatic hyperplasia (BPH), or an enlarged prostate gland, is a condition affecting half of men over age 50 and 80 percent of those over 70. Symptoms include difficult urination, sudden urges to urinate and inability to empty the bladder. BPH often is treated with medication and in severe cases open surgery may be necessary, but since 1997 transurethral microwave therapy has been a less-invasive option.

Transurethral microwave therapy involves using a catheter to place a microwave device within the prostate, which is then heated to destroy excess tissue. Approximately 70,000 such procedures are performed each year, usually in an office setting and typically involving patients from 50 to 85 years old.

“This patient population is at high risk of cardiovascular disease,” explains Benjamin Larson, a medical student at Cleveland Clinic who is the lead author of the Mayo Clinic Proceedings paper. “Anecdotal reports of adverse blood pressure events during and after transurethral microwave therapy, and our own experience, led us to look back at the records to identify potential problems among these patients whose blood pressure had been monitored.”

The authors say the study findings should not necessarily deter physicians and their patients from using one of the six FDA-approved devices for transurethral microwave therapy, but they should take reasonable precautions given the strong possibility of blood pressure surges. “Blood pressure monitoring should be a standard part of the procedure. Blood pressure readings should be taken throughout the procedure, multiple times. Unfortunately, that has not always been the practice for this office-based therapy,” Dr. Mynderse explains. “Monitoring will enable physicians to identify the problem and adjust treatment. Patients also should be encouraged to continue their anti-hypertensive medications, particularly beta blockers, as they prepare for the procedure.”

Mayo Clinic

Urinary dysfunction troubles men who undergo prostate removal

Men with prostate cancer who have their prostate removed cite sexual dysfunction as the most common side effect after surgery, but urinary dysfunction troubles these patients most, reports a University of Florida researcher. What’s more, many aren’t emotionally prepared to face these complications.

The study findings, published in a recent issue of Urologic Nursing, underscore the need for health-care practitioners to educate their patients about the physical and psychological effects the surgery will have on their everyday lives.

“The effects of this treatment are quite immediate and can lead to depression and frustration,” said Bryan Weber, Ph.D., A.R.N.P., an assistant professor in the UF College of Nursing and the study’s lead author. “After an initial diagnosis of prostate cancer, men may be so focused on eradicating the disease that they don’t realize the effects the treatment will have on their quality of life, both for them and their families.”

Prostate cancer is the No. 1 cancer among men, excluding skin cancer, and with more baby boomers reaching their 50s and 60s, it’s expected to grow even more prevalent, with more than 200,000 cases diagnosed in 2007. Given the various treatment options for prostate cancer, men who undergo radical prostatectomy may initially decide that the risk of physical dysfunction is worth the benefit of improved likelihood of survival. But many don’t know what to expect in the months after surgery, Weber said.

Physical side effects of prostate cancer treatment limit daily activities and may interfere with a man’s sense of masculinity and self-confidence. Urinary incontinence, for example, requires the use of pads that add considerable bulkiness to clothing and create concern about leakage and odor. Sexual dysfunction interferes with a man’s sense of self and may limit the relationship he has with his significant other, Weber said.

In the study, UF researchers evaluated 72 men six weeks after they underwent prostatectomy. In addition to measuring participants’ physical function and assessing whether they had urinary and bowel symptoms and sexual dysfunction, the researchers also evaluated measures of self-confidence, social support and uncertainty about the disease and treatment. Most participants were white, married and employed full-time or retired, and most had some college education.

Fifty-seven percent of the men reported low to moderate social support, indicating that many of the topics proved embarrassing for them to discuss with others, Weber said. The level of social support was significantly related to urinary problems, revealing that men with urinary incontinence may need more support than those with more control.

“Within the first 100 days of diagnosis, men may be so distressed and so focused on curing their cancer that they don’t focus on these side effects, which is what makes it imperative for health-care professionals to educate them on ways that their lives will change and how they can cope,” Weber said. “Almost immediately after treatment, men may experience depression, awkwardness and emasculation, which will have a great effect on their quality of life.”

Weber suggests that clinicians assess men and their support systems, identify changes in physical function that may occur as a result of treatment, and direct them to products and services designed to help them cope with the immediate effects of sexual dysfunction and urinary and bowel incontinence.

For example, Weber said numerous medications aim to ease sexual dysfunction, but many men may not realize the great expense associated with these drugs or be aware of their potential side effects. Similarly, a number of options for urinary incontinence exist, such as boxer shorts that are designed to hold urinary pads, lessening the embarrassment of having to wear such items.

“Education and counseling should be provided to these men to better inform and prepare patients for the physical side effects they are likely to experience postoperatively,” Weber said. “Since we know that men are less likely to rely on support groups or be more embarrassed to discuss these items with family and friends, it’s even more vital for health-care professionals to stress these issues and include options for patients. Men need to be introduced to different options, make choices and regain control over their lives.”

Health practitioners need to remember to thoroughly discuss the consequences of treatment with patients, and information should be tailored to each individual’s needs, said Joyce Davison, Ph.D., R.N., an assistant professor at the University of British Columbia Department of Urologic Sciences.

“Once diagnosed with prostate cancer, men vary with regard to the type and amount of information they wish to access and the degree of decision control they wish to have,” Davison said. “It is up to health-care professionals to assess and provide information and support accordingly.”

University of Florida

Finding Solutions for Erectile Dysfunction and Incontinence Following Treatment for Prostate Cancer

Men experiencing erectile dysfunction, also known as ED, and urinary incontinence following treatment for prostate cancer, need not suffer alone and in silence. If oral medications fail, men and their partners need to know that there are other highly effective alternatives. That is the important message Natan Bar-Chama, MD, and Neil H. Grafstein, MD, urologists on the staff of the Deane Prostate Health and Research Center, are hoping to communicate at a free community education seminar scheduled for Tuesday, December 11 at Mount Sinai Medical Center in New York City.

"At the Deane Center, we are committed to restoring sexual function following prostate cancer treatment,” says Dr. Bar-Chama. “Patients need to explore all their options. A treatment that is appropriate and effective for one individual might not be the best approach for another person. But regardless of the severity of the condition or the cause, there is a safe and effective treatment that will enable a man and his partner to resume enjoyable sexual relations.” Adds Dr. Grafstein, “There are minimally invasive surgical approaches that restore continence and eliminate the constant worry, fear of embarrassment and need for pads. Men can resume an active lifestyle and feel more confident.”

Along with an overview of the causes of erectile dysfunction and urinary incontinence and a discussion about the emotional impact of ED and incontinence on patients and their partners, Dr. Bar-Chama and Dr. Grafstein will be providing detailed information about a wide range of treatment options. Galen Bird, a prostate cancer survivor, and his wife Linda will also be on hand to tell their very personal story about the impact of ED and incontinence on a marriage and the road they’ve traveled. A question and answer session will follow the formal presentation.

The seminar, which is free and open to the public, will take place in the Goldwurm Auditorium, Icahn Medical Institute, 1425 Madison Avenue, 1st fl. (bet. 98th and 99th Sts.) Registration will begin at 6:00 pm and the program runs from
6:30 − 7:30 pm. Spouses and partners are encouraged to attend. Refreshments will be served.

It is estimated that one in 10 men − or over 30 million men in the U.S. − suffer from erectile dysfunction. And the prevalence is expected to increase as the population ages. According to the Journal of Urology, population projections for men aged 40 to 69 suggest that over 600,000 new cases of erectile dysfunction are expected annually. Erectile dysfunction is also associated with diabetes and hypertension, in addition to treatment for prostate cancer.

The most common cause of stress urinary incontinence − the unintentional release of urine during normal, everyday activities − in men is the partial or total removal of the prostate gland during treatment for prostate cancer, which can damage the bladder’s external sphincter muscle that controls urine flow. By 2008, it is estimated that over 207,000 surgeries for prostate cancer will be performed. The incontinence rates following these procedures are estimated to be as high as 31%. Although not life threatening, the condition can be emotionally devastating and have a major impact on quality of life. Even such everyday activities as lifting, light exercise, even sneezing or coughing can lead to fear, embarrassment, despair and shame.

Mount Sinai Medical Center

Reactions to 'false-positive' prostate cancer screenings assessed

Men who get a "false-positive" prostate cancer result—an abnormal screening test followed by a biopsy indicating no evidence of cancer—appear more likely to worry about their subsequent risk of cancer and report more problems with sexual function compared to men with normal screening results, according to a University of Iowa study.

The study findings, based on telephone surveys of 210 men, appear in the February online issue of the journal Urology. Prostate cancer is the most common non-skin malignancy diagnosed in men in the United States. The majority of men in the United States are screened beginning at age 50 with the prostate-specific antigen (PSA) test.

"This study emphasizes the importance of doctors' discussing the pros and cons of prostate cancer screening with patients," said the study's lead author David Katz, M.D., associate professor of internal medicine in the UI Roy J. and Lucille A. Carver College of Medicine, and of epidemiology in the UI College of Public Health.

"Because screening affects a large number of men relative to those who are expected to benefit from treatment, even a small adverse effect of apparently false-positive results on cancer-related worry and quality of life could have a substantial impact on public health," said Katz, who also is a staff physician and researcher with the Department of Veterans Affairs Iowa City Health Care System and its Center for Research in the Implementation of Innovative Strategies and Practices.

The study team interviewed 101 men who had normal PSA levels and 109 men who had an abnormal PSA reading or abnormal digital rectal examination, but whose biopsy for prostate cancer then was negative.

Men with false-positives were about three times as likely to report being at least somewhat worried about getting prostate cancer and nearly twice as likely to report being bothered by their sexual function.

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Prostate Brachytherapy Causes Fewer Side Effects than Surgery

Men with prostate cancer have a slightly better long-term side effects profile with radiation seed implants than they do with surgery, according to a study released today in the International Journal for Radiation Oncology*Biology*Physics, the official journal of ASTRO.

Doctors in France conducted the first-ever multi-institutional, comparative study of men with early stage prostate cancer to evaluate a man’s quality of life, treatment-related side effects and cost of the treatment based on the type of treatment the patient received: surgery or seed implants, both widely-accepted modes of treatment for early-stage prostate cancer. With prostate surgery, called a radical prostatectomy, a surgeon removes the prostate. During prostate brachytherapy, a radiation oncologist places radioactive seeds, similar to the size of a grain of rice, into the prostate to kill the cancer.

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