Tag Archive | "androgen deprivation therapy"

Radiotherapy And Androgen Deprivation More Beneficial Than Radiotherapy Alone in Some Prostate Cancer Patients

In a recent study funded by grants from the National Cancer Institute and published in the New England Journal of Medicine, it was reported that short-term androgen-deprivation therapy improves survival in men with intermediate-risk, localized prostate cancer.  From 1994 to 2001, one thousand seventy nine men with localized prostate cancer and prostate-specific antigen levels of 20 ng/mL or less were randomized to receive radiotherapy alone (992 patients) or radiotherapy plus four months of androgen-deprivation therapy (987 patients).

The overall ten-year survival rate was significantly higher with combination therapy than with radiation alone, and combination therapy decreased disease-specific deaths.  The median follow-up period was 9.1 years, and the ten-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group), as compared with 57% among patients receiving only radiotherapy.  The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from eight percent to four percent. Biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at two years were significantly improved with radiotherapy plus short-term ADT.  In the two groups, acute and late radiation-induced toxic effects were similar.

The study was carried out because it had not been known whether short-term androgen-deprivation therapy (ADT) before and during radiotherapy improves cancer control and overall survival among patients with early, localized prostate adenocarcinoma.

It was found in a post-hoc analysis that the benefits of combination therapy were limited to men with intermediate-risk disease rather than men with low-risk cancer.

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Hormone Therapy Used to Treat Prostate Cancer Increases Vertebral Fractures

A recent study found that androgen deprivation therapy (ADT), a hormone therapy that is used to treat prostate cancer, speeds up loss of bone mineral density and increases vertebral fractures, particularly in white men.  The study was published in the Journal of Urology.

The men in the study were enrolled in a fracture prevention trial for prostate cancer patients receiving ADT and were at least 70 years old or had low bone mineral density at the lumbar spine or total hip.

Lead author of the study, Philip J. Saylor, MD, of Boston’s Massachusetts General Hospital, and his colleagues studied 1244 men, including 162 (13%) who had a vertebral fracture at baseline.  Although white race, osteoporosis and low bone density were significantly associated with this finding, age, country of residence and body mass index were not.  According to Saylor, older age, low bone mineral density, and white race prompt patients and doctors to discuss preventative therapy.

The duration of ADT was also not linked to prevalent vertebral fractures, perhaps because the effect on bone mineral density is most apparent in the first year of therapy and the average duration at study entry was four years.

The authors concluded the article by stating that these observations should inform the assessment and management of fracture risk among such men.  Also, in a related editorial, Paul Maroni and E. David Crawford, MDs, of the University of Colorado Health Sciences Center in Denver emphasized the importance of assessing bone health before ADT given the frequency and urgency of the condition.

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Sexual Potency After Radiation Therapy for Prostate Cancer Stabilizes After Two Years

According to data from a prospective cohort study by Richard Valicenti, MD, of the University of California Davis and colleagues, sexual function declines in the first two years after external beam radiation therapy (EBRT) for prostate cancer but stabilizes thereafter.  Pretreatment sexual function was the strongest predictor of sexual function at any time after EBRT.  These findings were reported in the International Journal of Radiation Oncology.

These findings debunk the perception that sexual function declines continually after radiation therapy for prostate cancer.

Valicenti said that the results of the study allow patients and their partners to have a fuller understanding of long-term sexual side effects of EBRT and what they can expect after treatment should aid in deciding on a treatment course.

Reported rates of impotency after EBRT for prostate cancer have ranged from eight percent to 85 percent.  The authors attributed this variation to the different instruments used to assess sexual function.

Additionally, many studies included men who received androgen deprivation therapy with EBRT, possibly covering up the contributions of radiation therapy to changes in sexual function.  Many recent studies have suggested that rates of sexual dysfunction increase with follow-up, but few studies included pretreatment assessment of sexual function or conducted serial assessments of sexual function after EBRT.

The investigators prospectively followed 143 men who completed a sexual function questionnaire prior to EBRT for prostate cancer and at each follow-up visit.  The questionnaire assessed four domains of sexual function: sexual drive, erectile function, ejaculatory function, and overall satisfaction.  Scores on all four of these domains and the total score declined significantly in the first two years after EBRT compared to baseline values.  The average age of the patients was 69 year old.

During a median four years of follow-up, the patients completed 1,187 questionnaires.  Some participants were followed for as long as eight years after EBRT.  The baseline scores for sexual drive and erectile function were significantly correlated with age of patient.  Ejaculatory function was significantly correlated with age, race, and marital status.

The patients were grouped according to baseline sexual function.  The scores for the patients above and below the median sexual function value showed that differences in sexual function persisted over time.  Baseline score was the best predictor of later scores for all of the domains assessed.

There were indications that 74.1 percent of the study participants were sexually potent before EBRT.  Of these patients, 74.4 percent remained potent at one year and 70.4 percent at two years after EBRT.  There were no statistically significant changes in potency from year’s two to six.

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Prostate Cancer Survival Rate Improves with Short Term Hormone Therapy Coupled with Radiation Therapy

A new study published by the Radiation Therapy Oncology Group (RTOG) in the New England Journal of Medicine and supported by grants from the National Cancer Institute found that short-term hormone therapy (androgen deprivation therapy –ADT) given in combination with radiation therapy for me in early-state prostate cancer increases their chance of surviving longer and not dying from the cancer.  This was the largest randomized trial of its kind, enrolling almost 2,000 men at low and intermediate risk of prostate cancer progression and following their health status from October 1994 to April 2001 at 212 centers throughout the United States and Canada.

Male hormones (androgens) including testosterone increase the growth of prostate cancer cells.  Therapy that decreases the body’s levels of androgens (particularly four months of ADT starting two months prior to radiation therapy in this study) removes the strongest growth factor for prostate cancer cells.  Authors of the study report that adding short-term ADT to radiation therapy significantly improved the overall survival rate at 10 years from 57 to 62 percent.  Additionally, in a trial of different treatments on each of the patients’ two arms, the radiation therapy coupled with short-term ADT arm was associated with four percent fewer prostate cancer-related mortalities compared with the radiation therapy-alone arm.  More importantly, the reduction in disease-specific deaths was accounted for by the intermediate-risk study participants in the radiation therapy plus ADT arm (10 percent as opposed to three percent in radiation only arm at 10 years) while no reduction in deaths was seen among low-risk participants at 10 years.  These benefits were achieved with a mild increase in patient-reported erectile dysfunction at one year but no increase in observed long-term bowel or bladder toxicities.

About 240, 890 Americans will be diagnosed with prostate cancer in 2011 and almost 9 out of 10 will have early-stage disease.

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Investigational Drug Cabozantinib Active Against Advanced Prostate Cancer

When prostate cancer stops responding to androgen deprivation therapy (ADT), it is referred to as hormone-refractory prostate cancer.  Although advances have been made in the treatment of hormone-refractory prostate cancer, challenges remain and new drugs continue to be developed.

An investigational drug called Cabozantinib is showing promise in the treatment of hormone-refractory prostate cancer particularly among patients with bone metastases.

Researchers conducted a Phase II clinical trial among 171 patients with progressive cancer in which more than three-quarters of the men had bone metastases. All patients were initially treated with 12 weeks of Cabozantinib. On bone scan, 76% of the patients with bone metastases had partial or complete disappearance of the bone metastases. For patients taking narcotics for bone pain, 67% had a reduction in pain and 56% decreased or stopped their narcotic use.  More than two thirds of patients had some reduction in metastases outside of the bone.

Side effects include fatigue, gastrointestinal symptoms and high blood pressure.

These results were presented at the 2011 annual meeting of the American Society of Clinical Oncology.

Additional studies are underway.

Cabozantinib has not yet been approved by the U.S. Food and Drug Administration.

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No Significant Association Found Between Androgen Deprivation Therapy and Cardiovascular Death

Treatment with androgen deprivation therapy (ADT) does not significantly increase the risk of cardiovascular mortality according to evaluation of mortality data in a large registry of men treated for prostate cancer.

ADT is commonly used to treat prostate cancer.  Some studies have shown that it may increase the risk of cardiovascular disease, but other studies have not confirmed the association and it remains controversial.  The authors of the recent study tried to explore the evidence further by analyzing the patients registry CAPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor), which includes men with confirmed prostate cancer recruited from 40 mostly community-based US urological practices.

Men who are diagnosed with localized prostate cancer between 1995 and 2007 were included in the analysis, and in order to try to control for factors that may confound the relationship between ADT and cardiovascular death, patients who used and did not use ADT were matched by their propensity to receive ADT.  These patients were categorized into three groups: primary ADT monotherapy, local treatment plus ADT, and watchful waiting/active surveillance (WW/AS).  Initial outcomes were associations between treatment and cardiovascular cause, prostate cancer, and other causes.  Study investigators assessed cause of death using death certificates.

At the point of data capture, there were 13,887 men in the registry, of whom 7,248 were eligible for the analysis.  The majority (71.3%) received local treatment only, 6.7% received local treatment plus ADT, 15% received primary ADT, and 7 percent WW/AS.  It was found that 21.7% received AFT at some point.  Nine hundred seventy six of these men died during the study period, 1.4% from prostate cancer, 2.7% from cardiovascular disease, and 9.4 percent due to other causes.  Patients treated with ADT or WW/AS had a higher likelihood of death due to prostate cancer than those treated just with local therapy.

The largest risk of cardiovascular death was in those treated with WW/AS compared to those only receiving local therapy.  The difference for those treated with local therapy plus ADT was not significant.

The authors’ conclusion is that the increased rate of cardiovascular death in the WW/AS group compared to the ADT group suggests that there are possibly unmeasured variables that affect treatment selection and that confound the association between ADT and cardiovascular death.  The research team notes that when patients were match on propensity to receive ADT, there was no significant association.  The limitation so the study included the relatively small number of deaths in some groups, and the assignment of cause of death from death certificates.

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Prostate Therapy Increases Colon Cancer Risk

A recent study is finding that patients on long-term androgen deprivation therapy (ADT) for prostate cancer have an increased risk of colorectal cancer compared with patients who do not receive ADT.

One type of ADT, orchiectomy, showed the greatest impact on the risk of colorectal cancer, whereas GnRH treatment had a more modest affect.  The Journal of the National Cancer Institute has published an article concerning the study stating that those who participated in the study had a 30% to 40% increased risk of colorectal cancer.  Further, the risk increased with the duration of the treatment, no matter the type of ADT the patients received.

“The study results have important implications for men with prostate cancer who are receiving or contemplating initiation of androgen deprivation therapy,” Silke Gillessen, MD, of the University of Michigan in Ann Arbor, and co-authors wrote in the discussion of their findings.

“Despite a moderate relative risk for colorectal cancer, the impact may nevertheless be large, given that hundreds of thousands of men are on androgen deprivation therapy for prostate cancer.”

The findings of this new study may prove to be incredibly significant, especially when the results are extended to the broader issue of androgen deficiency, which affects an estimated 2.4 million men in the U.S. at an annual rate of 500,000.

The interest in the link between colorectal cancer and ADT began with the discovery of monozygotic twins who developed colon cancers following ADT for prostate cancer.  The investigators decided to observe a larger patient base in order to decide whether or not the discovery had broader implications.  Gillessen and co-authors searched the Medicare-linked Surveillance, Epidemiology, and End Results database for men who had newly diagnosed prostate cancer from 1993 through 2002.

After limiting the search to men ages 67 and older at diagnosis, the authors identified 107,859 men who had follow-up through 2004.  Of those, 55,901 received ADT during the study period, including 50,097 treated with GnRH agonists and 5,804 patients who underwent orchiectomy.

Prostate cancer patients who did not receive ADT had an unadjusted colorectal cancer rate of 3.7 cancers per 1,000 person-years.

With GnRH therapy, the rate increased to 4.4 cancers per 1,000 person-years, and then to 6.3 cases per 1,000 person-years among the men who underwent surgical castration.

“This pattern was generally consistent within strata of patient and prostate cancer characteristics,” the authors noted.

Examination of colorectal cancer risk as a function of ADT duration showed a gradient of increasing risk as the duration of ADT increased.  For those who received ADT therapy for 24 months or less, the risk was less when compared to those who received the therapy for 25 months or greater.

According to the authors, “This study provides strong evidence to link androgen deprivation therapy in the setting of prostate cancer to an increased risk of colorectal cancer.”  They added, “There was also a statistically significant dose-response effect, with a higher risk of colorectal cancer with an increasing duration of androgen deprivation, providing support that the observed association between androgen deprivation and colorectal cancer by may causal.”

The findings of this recent study are important to consider when deciding if ADT is an appropriate therapy for prostate cancer for many patients.  All physicians must weigh the benefits versus costs of any therapy for their patients, and results like these cannot be ignored.

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July 2019
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