Side Effects Of Androgen Deprivation Research Articles

Influence of abiraterone and enzalutamide on body composition in patients with metastatic castration resistant prostate cancer

Loss of skeletal muscle (SM) and gain of subcutaneous fat (SCF) are known side-effects of androgen-deprivation in treatment of prostate cancer. Scarce data is available concerning the effects of abiraterone/pred (ABI) on body composition and no published data regarding enzalutamide (ENZA). Our objective was to analyse the effects of ENZA on SM/SCF and to compare the results with ABI in patients with metastatic castration-resistant prostate-cancer (mCRPC). 54 patients starting ABI (n=17) or ENZA (n=37) at a single-centre between 2012 and 2018 were retrospectively identified. SM and SCF were assessed using CT-scans at baseline and after a median of 10.8 months on treatment. A deep learning image-segmentation software was used to quantify SM and SCF. In a subgroup of patients receiving ENZA within a trial, we investigated change of SM using serial timepoints. Median time of treatment with ABI/ENZA was 14.6 months. A significant loss of SM compared to baseline was observed for ENZA (mean loss 5.2%, p<0.0001) and ABI (mean loss 3.0%, p=0.02). SCF was not significantly altered. The effects of both drugs did not differ significantly. Loss of SM occurred early on during treatment with ENZA. Treatment with ENZA seems to lead to a loss of SM which is comparable to that of ABI. Further evaluation in larger patient-cohorts is warranted. In routine care, counselling of patients about side effects of ABI/ENZA should include discussions about SM loss.

961 - Updated Analysis of a Combination Herbal Supplement Trial in Biochemically Recurrent Prostate Cancer

ABSTRACT Background After curative local therapy, thousands of men will experience rising PSA as an early indicator of recurrent prostate cancer. For these men no standard of care exists, and concern over serious side effects of androgen deprivation (ADT) makes delaying ADT common. We tested Prostate Health Cocktail (PHC), which contains vitamins D & E, saw palmetto, lycopene, green tea and soy extracts, in this population, to see whether it could induce PSA declines. Methods Eligible men had a rising PSA with doubling time (DT) between 3 and 36 months, with no evidence of metastases on CT and bone scan. Treatment included PHC 3 capsules PO daily for 4 week cycles for a maximum of 1 year. PSA was repeated after 1 cycle and then every 2 cycles thereafter with imaging only as clinically indicated; the primary endpoint was PSA decline at 12 weeks. PSA progression was defined as 25% increase above baseline/nadir and absolute increase of 5 ng/mL or return to baseline. Circulating tumor cells (CTCs) were measured at baseline and after 3 cycles using parylene membrane filters. Results A total of 36 patients were enrolled as of January 31, 2012; 3 were retrospectively classified as ineligible and were excluded from all analyses except for toxicity. The median age was 67 (range 54-85) and baseline PSA was 2.9 ng/mL (1.1-53.2). The median number of cycles was 8 (1-13). Stable PSA was the best response for 25/27 men assessable at 12 weeks (93%) and 11/33 men (33%) had a PSA decline (1.1%-49.0% decrease). There was no significant change in testosterone or DHT during treatment. Circulating tumor cells were detected in some of the subjects. One patient had grade 3 transaminitis in the setting of alcohol consumption, otherwise the toxicities were limited to grade 1 or 2 and related to the gastrointestinal and metabolic/laboratory systems. Conclusion PHC demonstrated activity in men with biochemical recurrence, resulting in PSA declines in about a third of cases, and was not associated with changes in serum androgens or significant toxicities. For the first time, we are reporting that circulating tumor cells can be detected in men with biochemical recurrence using filter technology. Disclosure J. Pinski: I am a co-owner of OncoNatural Solutions Inc, the company which produces the Prostate Heath Coctail (PHC). All other authors have declared no conflicts of interest.

A combination herbal supplement for biochemically recurrent prostate cancer.

24 Background: After curative local therapy, thousands of men will have rising PSA as an early indicator of recurrent prostate cancer. For them, no standard of care exists, and concern over serious side effects of androgen deprivation (ADT) makes delaying ADT common. We tested Prostate Health Cocktail (PHC), which contains vitamins D &amp; E, saw palmetto, lycopene, green tea and soy extracts, in this population, to see whether it could induce PSA declines. Methods: Eligible men had rising PSA with doubling time (DT) 3-36 months, with no evidence of metastases on CT and bone scans. After IRB approval, 28 men were treated with PHC 3 capsules PO daily for 4 week cycles. PSA was repeated after the first cycle, then every 2 cycles with imaging only as clinically indicated; the primary endpoint was PSA decline. PSA progression was defined as 25% increase and absolute increase of 5 ng/mL or return to baseline. Circulating tumor cells (CTCs) were measured at baseline and after 3 cycles using parylene membrane filters. Results: The median age was 67 (range 54-84) and baseline PSA was 2.9 ng/mL (1.1-53.2); the median number of cycles was 6 (1-13). Stable PSA was the best response for 23/28 men (83%) and 8/27 men (29.6%) had a PSA decline (1.1%-29.4% maximum decrease). 47% stopped therapy for progression with median time to progression=9.2 months. There was no association between Gleason score or baseline PSA, vitamin D or selenium level and PSA decline. CTCs were detected in 5 of the first 23 subjects. The median PSA for these men was 2.77 ng/mL (range 1.63-16.8). There was no significant change in testosterone or DHT during treatment. Median PSA DT at baseline was 7.8 months (range 3-36). One patient had grade 3 transaminitis in the setting of alcohol consumption, otherwise toxicities were limited to grade 1 or 2 hypercalcemia(1), hyperkalemia(2), hyperglycemia(4), flatulence(4), other GI(5), and rash(1). Conclusions: PHC demonstrated activity in men with biochemically recurrent prostate cancer, resulting in PSA declines in nearly a third of cases, and was not associated with changes in serum androgens or significant toxicities. For the first time, we are reporting that circulating tumor cells can be detected in men with biochemical recurrence using filter technology.

Side effects of androgen deprivation and their management

Les effets secondaires de la deprivation androgenique sont de mieux en mieux connus. A cote des bouffees de chaleur et de la dysfonction erectile, les complications cardiovasculaires et osseuses doivent etre prises en compte a la fois dans les indications des medicaments mais aussi dans la surveillance du traitement. L’induction d’un diabete peut etre un evenement precoce, survenant dans les six mois apres le debut du traitement. Les dyslipidemies sont plus rares. L’augmentation de la frequence des accidents cardiovasculaires ou de la mortalite cardiaque reste discutee. Il est maintenant bien demontre que la deprivation androgenique augmente de maniere moderee le risque d’evenements osseux de type osteoporotique. Cette meilleure connaissance des effets secondaires necessite la realisation d’un bilan clinique et paraclinique initial et lors de la surveillance d’une hormonotherapie prolongee.

Hormonal Therapy in the Elderly Prostate Cancer Patient: In reply

In the context of the question raised in our article, the primary treatment cited by Egidi is one form or another of androgen deprivation. If tumor progression occurs in spite of this treatment, then, without taking recourse to laboratory tests (total PSA, possibly sarcosine concentrations in urine), local symptoms such as obstructive micturition problems or indications of systemic progression such as bone pain can be expected. All that’s left by way of therapeutic options then is palliative treatment-for example, transurethral prostatic resection, focal irradiation, or analgesic medication. Whether it is beneficial for a patient who is having hormone therapy and regular PSA tests to detect the progression before onset of symptoms is a legitimate question. In any case, PSA testing helps to detect the point at which the selected primary hormone therapy becomes ineffective and should be stopped. Such an approach does not need to be confirmed by a study, because the patient is spared at least the side effects of androgen deprivation up to the point where symptoms of progression manifest. If the patient receives an antiandrogen as primary treatment then one third of patients experience improvement when the antiandrogen is stopped. Subsequently, secondary hormone therapy should be given, which is by no means ineffective. The comprehensive range of secondary hormone treatments in PSA progression has recently been shown (1). For the future, the task is to detect castration resistant prostate cancer by regularly testing PSA values. Currently, phase III studies are investigating the option of androgen receptor manipulation.

A phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer

BackgroundAndrogen deprivation therapy (ADT) is accompanied by a number of adverse side effects including reduced bone mass and increased risk for fracture, reduced lean mass and muscle strength, mood disturbance and increased fat mass compromising physical functioning, independence, and quality of life. The purpose of this investigation is to examine the effects of long term exercise on reversing musculoskeletal-related side effects, and cardiovascular and diabetes risk factors in men receiving androgen deprivation for their prostate cancer. Specifically, we aim to investigate the effects of a 12-month exercise program designed to load the musculoskeletal system and reduce cardiovascular and diabetes disease progression on the following primary endpoints: 1) bone mineral density; 2) cardiorespiratory function and maximal oxygen capacity; 3) body composition (lean mass and fat mass); 4) blood pressure and cardiovascular function; 5) lipids and glycemic control; and 6) quality of life and psychological distress.Methods/DesignMulti-site randomized controlled trial of 195 men (65 subjects per arm) undergoing treatment for prostate cancer involving ADT in the cities of Perth and Brisbane in Australia. Participants will be randomized to (1) resistance/impact loading exercise, (2) resistance/cardiovascular exercise groups and (3) usual care/delayed exercise. Participants will then undergo progressive training for 12 months. Measurements for primary and secondary endpoints will take place at baseline, 6 and 12 months (end of the intervention).DiscussionThe principal outcome of this project will be the determination of the strength of effect of exercise on the well established musculoskeletal, cardiovascular and insulin metabolism side effects of androgen deprivation in prostate cancer patients. As this project is much longer term than previous investigations in the area of exercise and cancer, we will gain knowledge as to the continuing effects of exercise in this patient population specifically targeting bone density, cardiovascular function, lean and fat mass, physical function and falls risk as primary study endpoints. In terms of advancement of prostate cancer care, we expect dissemination of the knowledge gained from this project to reduce fracture risk, improve physical and functional ability, quality of life and ultimately survival rate in this population.Clinical Trial RegistryA Phase III clinical trial of exercise modalities on treatment side-effects in men receiving therapy for prostate cancer; ACTRN12609000200280

Modern-Day Eunuchs: motivations for and consequences of contemporary castration

This article compares the motivations for, and responses to, castration between two groups of males: prostate cancer patients and voluntary modern-day eunuchs with castration paraphilias or other emasculating obsessions. Prostate cancer patients are distressed by the side effects of androgen deprivation and typically strive to hide or deny the effects of castration. In contrast, most voluntary eunuchs are pleased with the results of their emasculations. Despite a suggested association of androgen deprivation with depression, voluntary eunuchs appear to function well, both psychologically and socially. Motivation, rather than physiology, appears to account for these different responses to androgen deprivation.

Endocrine treatment of prostate cancer

Although androgen deprivation as a treatment for patients with prostate cancer was described more than 60 years ago its optimal use remains controversial. The widespread use of prostate-specific (PSA) assay has lead to earlier diagnosis and earlier detection of recurrent disease. This means that the systemic side effects of androgen deprivation and quality of life have become more important. Debates continue regarding the proper use and timing of endocrine therapy with orchiectomy, oestrogen agonists, gonadotropin hormone-releasing hormone (GnRH) agonists, GnRH antagonists, and androgen antagonists. A critical review of the literature was performed. Data support that androgen deprivation is an effective treatment for patients with advanced prostate cancer. However, although it improves survival, it is not curative, and creates a spectrum of unwanted effects that influence quality of life. Castration remains the frontline treatment for metastatic prostate cancer, where orchiectomy, oestrogen agonists and GnRH agonists produce equivalent clinical responses. Maximum androgen blockade (MAB) is not significantly more effective than single agent GnRH agonist or orchiectomy. Nonsteroidal antiandrogen monotherapy is as effective as castration in treatment of locally advanced prostate cancer offering quality of life benefits. Adjuvant endocrine treatment is able to delay disease progression at any stage. There is, however, controversy of the possible survival benefit of such treatment, including patients having PSA relapse after definitive local treatment for prostate cancer. Neoadjuvant endocrine treatment has its place mainly in the external beam radiotherapy setting. Intermittent androgen blockade is still considered experimental. The decision regarding the type of androgen deprivation should be made individually after informing the patient of all available treatment options, including watchful waiting, and on the basis of potential benefits and adverse effects. Several large studies are under way to investigate the role of adjuvant endocrine treatment in the field of early prostate cancer, intermittent androgen deprivation and endocrine therapy alone compared with endocrine therapy with radiotherapy. The real challenge, however, is to develop better means to avert hormone-refractory prostate cancer and better treatments for patients with hormone-refractory disease when it occurs.

Flutamide Versus Orchidectomy in the Treatment of Metastatic Prostate Carcinoma

To compare in a randomized clinical trial the therapeutic efficacy of the nonsteroidal antiandrogen flutamide 250 mg tid to testicular androgen suppression by orchidectomy in patients with metastatic prostate cancer.Between 1989 and 1991, 104 patients aged 74 +/- 8 years with newly diagnosed metastatic prostate cancer, an ECOG performance status 0-2 and no prior hormone manipulation or chemotherapy, were randomized to receive flutamide 250 mg tid (54 patients) or orchidectomy (50 patients). Patients were evaluated at entry and at months 3, 6, 12, 18 and 24. The primary endpoint was duration of progression-free survival, progression being defined as an increase in PSA> 50% over the nadir value at 2 consecutive months or a single PSA rise > 50% over the nadir value with another objective parameter. At progression, the treatment was left to the discretion of the attending urologist.16 patients (10 flutamide, 6 orchidectomy) are not evaluable. 86 had a minimum follow-up of 36 months, 36/42 and 41/44 have progressed in the orchidectomy and flutamide group with a time of failure of 419 and 496 days (p = 0.32); median time to progression was almost identical in both groups (370 vs. 396 days p = 0.9); overall survival at 69 months irrespective of treatment at relapse was identical in both groups. Side effects were dominated by gynecomastia, hot flushes in both groups, breast tenderness and diarrhea in the flutamide group. Overall, 4 (10%) of the patients in the flutamide group withdrew from therapy because of side effects. The impact of flutamide on sexual potency was not assessed because of the advanced age of the patients. Serum testosterone rose by 50% over baseline level at month 3 to plateau at 25% over baseline level at month 12.Although affected by the lack of a clear statistical power due to the small number of patients in each arm, this study shows that in spite of a constant elevation of serum testosterone (25% over baseline) flutamide 250 mg tid may be a reasonable alternative to castration in highly selected patients with well to moderately differentiated low volume metastatic prostate cancer and wishing to avoid the side effects of androgen deprivation, provided they are closely monitored and ready to switch to standard androgen deprivation in the presence of untolerable side effects or suboptimal treatment efficacy as assessed by the inability to achieve a low PSA nadir.

Flutamide versus Orchidectomy in the Treatment of Metastatic Prostate Carcinoma

To compare in a randomized clinical trial the therapeutic efficacy of the nonsteroidal antiandrogen flutamide 250 mg tid to testicular androgen suppression by orchidectomy in patients with metastatic prostate cancer. Between 1989 and 1991, 104 patients aged 74 +/- 8 years with newly diagnosed metastatic prostate cancer, an ECOG performance status 0-2 and no prior hormone manipulation or chemotherapy, were randomized to receive flutamide 250 mg tid (54 patients) or orchidectomy (50 patients). Patients were evaluated at entry and at months 3, 6, 12, 18 and 24. The primary endpoint was duration of progression-free survival, progression being defined as an increase in PSA> 50% over the nadir value at 2 consecutive months or a single PSA rise > 50% over the nadir value with another objective parameter. At progression, the treatment was left to the discretion of the attending urologist. 16 patients (10 flutamide, 6 orchidectomy) are not evaluable. 86 had a minimum follow-up of 36 months, 36/42 and 41/44 have progressed in the orchidectomy and flutamide group with a time of failure of 419 and 496 days (p = 0.32); median time to progression was almost identical in both groups (370 vs. 396 days p = 0.9); overall survival at 69 months irrespective of treatment at relapse was identical in both groups. Side effects were dominated by gynecomastia, hot flushes in both groups, breast tenderness and diarrhea in the flutamide group. Overall, 4 (10%) of the patients in the flutamide group withdrew from therapy because of side effects. The impact of flutamide on sexual potency was not assessed because of the advanced age of the patients. Serum testosterone rose by 50% over baseline level at month 3 to plateau at 25% over baseline level at month 12. Although affected by the lack of a clear statistical power due to the small number of patients in each arm, this study shows that in spite of a constant elevation of serum testosterone (25% over baseline) flutamide 250 mg tid may be a reasonable alternative to castration in highly selected patients with well to moderately differentiated low volume metastatic prostate cancer and wishing to avoid the side effects of androgen deprivation, provided they are closely monitored and ready to switch to standard androgen deprivation in the presence of untolerable side effects or suboptimal treatment efficacy as assessed by the inability to achieve a low PSA nadir.