-
1.
Nutrition care guidelines for men with prostate cancer undergoing androgen deprivation therapy: do we have enough evidence?
Barnes, KA, Ball, LE, Galvão, DA, Newton, RU, Chambers, SK
Prostate cancer and prostatic diseases. 2019;(2):221-234
Abstract
BACKGROUND To review the evidence available to support clinical practice guidelines for dietary interventions aimed at mitigating the side effects of androgen deprivation therapy (ADT) in men with prostate cancer, and to identify future research priorities. METHODS An analytical model was designed to select and interpret evidence for the effect of dietary interventions on ADT side effects. Key terms identified articles that investigated dietary interventions to mitigate ADT side effects among men treated for prostate cancer. Medline, Embase, Proquest, CINAHL, Cochrane databases, and PubMed were searched from inception through June, 2018. Clinical trial registries were also searched for up-to-date study protocols. Articles were not restricted on design. Methodological quality was assessed using the mixed methods appraisal tool. RESULTS Sixteen articles met inclusion criteria, each with distinct dietary interventions. Twelve studies used interventions that combined diet with physical activity and/or medication and/or counselling. Four articles examined the effect of diet alone on ADT side effects. Of those, three articles measured changes to participants' dietary intake and influence on ADT side effects. One article showed daily caffeinated beverages improved cancer-related fatigue. Two articles showed no impact of isoflavone supplementation on hot flushes, quality of life, body mass index, or blood lipids. Dietary intake and compliance was poorly reported across all studies limiting knowledge of acceptability and feasibility for dietary interventions. Information on the nutrition care practices and views of clinicians treating men for prostate cancer is limited. No articles measured the impact of diet on long-term ADT side effects. Methodological quality of included papers ranged from weak to strong. CONCLUSIONS Current evidence for dietary interventions to mitigate ADT side effects is limited. Further investigations are warranted to explore the impact of changes in dietary intake on ADT side effects before practice guidelines can be considered.
-
2.
HSD3B1 status as a biomarker of androgen deprivation resistance and implications for prostate cancer.
Hettel, D, Sharifi, N
Nature reviews. Urology. 2018;(3):191-196
Abstract
Patients with advanced prostate cancer who receive androgen deprivation therapy (ADT) almost invariably develop castration-resistant disease. The mechanism of resistance is largely based on synthesis of intratumoral androgens from adrenal precursors, requiring enzymatic action of 3β-hydroxysteroid dehydrogenase/Δ5→4 isomerase 1 (3β-HSD1), encoded by HSD3B1. A nucleotide polymorphism (1245A>C) in HSD3B1 results in a protein variant with increased steady-state levels and subsequently increased androgen synthesis from extragonadal precursors. Multiple clinical studies have shown that patients with the variant allele have significantly worse outcomes after ADT than those without, indicating that HSD3B1 variant status is a predictive biomarker of shortened ADT response. In addition, inheritance of the HSD3B1 variant is associated with extended responses to 17α-hydroxylase/17,20-lyase (CYP17A1) inhibition with a nonsteroidal agent, adding to evidence of increased tumour dependence on extragonadal androgens in patients who inherited the HSD3B1 variant. However, steroidal drugs with a 3β-hydroxyl, Δ5-structure, such as abiraterone, are also metabolized by 3β-HSD1, and 5α-abiraterone, a downstream metabolite, has been shown to activate the androgen receptor, potentially driving cancer progression. These data indicate a potential requirement to modify the treatment framework of patients harbouring variant HSD3B1.
-
3.
[Metabolic complications of androgen deprivation therapy and its intervention management].
Hu, YH, Wu, S, Zhang, M
Zhonghua nan ke xue = National journal of andrology. 2018;(3):277-281
Abstract
Androgen deprivation therapy (ADT) is one of the dominant treatment options for advanced prostate cancer, which has been certified to significantly improve the overall survival of prostate cancer patients. However, it sometimes can also produce severe adverse effects on body metabolism. This review summarizes the adverse effects of ADT on body composition, the levels of cholesterol and blood glucose, and the cardiovascular system, and the intervention management of these metabolic complications as well.
-
4.
Pharmacological interventions for the prevention of insufficiency fractures and avascular necrosis associated with pelvic radiotherapy in adults.
van den Blink, QU, Garcez, K, Henson, CC, Davidson, SE, Higham, CE
The Cochrane database of systematic reviews. 2018;(4):CD010604
-
-
Free full text
-
Abstract
BACKGROUND Pelvic radiotherapy is a treatment delivered to an estimated 150,000 to 300,000 people annually across high-income countries. Fractures due to normal stresses on weakened bone due to radiotherapy are termed insufficiency fractures. Pelvic radiotherapy-related interruption of the blood supply to the hip is termed avascular necrosis and is another recognised complication. The reported incidences of insufficiency fractures are 2.7% to 89% and risk of developing avascular necrosis is 0.5%. These complications lead to significant morbidity in terms of pain, immobility and consequently risk of infections, pressure sores and mortality. OBJECTIVES To assess the effects of pharmacological interventions for preventing insufficiency fractures and avascular necrosis in adults over 18 years of age undergoing pelvic radiotherapy. SEARCH METHODS We performed electronic literature searches in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and DARE to 19 April 2017. We also searched trial registries. Further relevant studies were identified through handsearching of citation lists of included studies. SELECTION CRITERIA Randomised controlled trials (RCTs) or non RCTs with concurrent comparison groups including quasi-RCTs, cluster RCTs, prospective cohort studies and case series of 30 or more participants were screened. We included studies assessing the effect of pharmacological interventions in adults over 18 years of age undergoing radical pelvic radiotherapy as part of anticancer treatment for a primary pelvic malignancy. We excluded studies involving radiotherapy for bone metastases. We assessed use of pharmacological interventions at any stage before or during pelvic radiotherapy. Interventions included calcium or vitamin D (or both) supplementation, bisphosphonates, selective oestrogen receptor modulators, hormone replacement therapy (oestrogen or testosterone), denosumab and calcitonin. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial quality and extracted data. We contacted study authors to obtain missing data. Data were to be pooled using the random-effects model if study comparisons were similar, otherwise results were to be reported narratively. MAIN RESULTS We included two RCTs (1167 participants). The first RCT compared zoledronic acid with placebo in 96 men undergoing pelvic radiotherapy for non-metastatic prostate cancer.The second RCT had four treatment arms, two of which evaluated zoledronic acid plus adjuvant androgen suppression compared with androgen suppression only in 1071 men undergoing pelvic radiotherapy for non-metastatic prostate cancer.Both studies were at a moderate to high risk of bias and all evidence was judged to be of very low certainty.The studies provided no evidence on the primary outcomes of the review and provided limited data in relation to secondary outcomes, such that meta-analyses were not possible. Both studies focused on interventions to improve bone health in relation to androgen deprivation rather than radiation-related insufficiency fractures and avascular necrosis. Few fractures were described in each study and those described were not specific to insufficiency fractures secondary to radiotherapy. Both studies reported that zoledronic acid in addition to androgen deprivation and pelvic radiotherapy led to improvements in BMD; however, the changes in BMD were measured and reported differently. There was no available evidence regarding adverse effects. AUTHORS' CONCLUSIONS The evidence relating to interventions to prevent insufficiency fractures and avascular necrosis associated with pelvic radiotherapy in adults is of very low certainty. This review highlights the need for prospective clinical trials using interventions prior to and during radiotherapy to prevent radiation-related bone morbidity, insufficiency fractures and avascular necrosis. Future trials could involve prospective assessment of bone health including BMD and bone turnover markers prior to pelvic radiotherapy. The interventions for investigation could begin as radiotherapy commences and remain ongoing for 12 to 24 months. Bone turnover markers and BMD could be used as surrogate markers for bone health in addition to radiographic imaging to report on presence of insufficiency fractures and development of avascular necrosis. Clinical assessments and patient reported outcomes would help to identify any associated adverse effects of treatment and quality of life outcomes.
-
5.
Metabolic changes in patients with prostate cancer during androgen deprivation therapy.
Mitsuzuka, K, Arai, Y
International journal of urology : official journal of the Japanese Urological Association. 2018;(1):45-53
Abstract
Androgen deprivation therapy continues to be widely used for the treatment of prostate cancer despite the appearance of new-generation androgen-receptor targeting drugs after 2000. Androgen deprivation therapy can alleviate symptoms in patients with metastatic prostate cancer and might have a survival benefit in some patients, but it causes undesirable changes in lipid, glucose, muscle or bone metabolism. These metabolic changes could lead to new onset or worsening of diseases, such as obesity, metabolic syndrome, diabetes mellitus, cardiovascular disease, sarcopenia or fracture. Several studies examining the influence of androgen deprivation therapy in Japanese patients with prostate cancer also showed that metabolic changes, such as weight gain, dyslipidemia or fat accumulation, can occur as in patients in Western countries. Efforts to decrease these unfavorable changes and events are important. First, overuse of androgen deprivation therapy for localized or elderly prostate cancer patients should be reconsidered. Second, intermittent androgen deprivation therapy might be beneficial for selected patients who suffer from impaired quality of life as a result of continuous androgen deprivation therapy. Third, education and instruction, such as diet or exercise, to decrease metabolic changes before initiating androgen deprivation therapy is important, because metabolic changes are likely to occur in the early androgen deprivation therapy period. Fourth, routine monitoring of weight, laboratory data or bone mineral density during androgen deprivation therapy are required to avoid unfavorable events.
-
6.
[Endocrine therapy for prostate cancer.].
Nagaya, N, Horie, S
Clinical calcium. 2018;(11):1527-1533
Abstract
Endocrine therapy for prostate cancer is androgen deprivation therapy and antiandrogens, which are the standard treatment for advanced prostate cancer. Endocrine therapy is effective in most prostate cancers, but as treatment continues, most patients eventually experience resistant to endocrine therapy and disease progression. Patients in this state are said to have castration-resistant prostate cancer. This review outlines the types of endocrine therapy for prostate cancer, the physiological mechanisms of endocrine therapy, its clinical use in Japan and the United States and Europe, new endocrine therapy for castration-resistant prostate cancer, and the side effects to be noted in endocrine therapy.
-
7.
Optic neuritis secondary to antiandrogen therapy.
Ní Mhéalóid, Á, Cunniffe, G
Irish journal of medical science. 2017;(3):565-570
Abstract
BACKGROUND Optic neuropathy is a disorder characterised by dysfunction or destruction of the optic nerve tissues. Acquired causes include interruption in the blood supply, nutritional deficiency, compression by a tumour or aneurysm, trauma, and toxic types (Ambizas and Patel In US Pharm 36(4):HS2-HS6, 1). Drug-induced optic neuropathy is of the toxic type and can be defined as a clinical syndrome characterised by papillomacular bundle damage, central, or cecocentral scotoma, and reduced colour vision (Ambizas and Patel In US Pharm 36(4):HS2-HS6, 2011; Sharma and Sharma In Indian J Ophthalmol 59(2):137-141, 2). AIM: To report a case unilateral optic neuritis, secondary to the use of the antiandrogen, cyproterone acetate. CASE REPORT A 21-year-old female presented with a 4-day history of right brow pain exacerbated by eye movement, and blurring of the right temporal field of vision. She had been taking desogestrel 75 mg and cyproterone acetate 50 mg for the previous 2 months for hormone imbalance. Unaided right visual acuity measured 6/9 and unaided left visual acuity measured 6/6 on Snellen chart. Right red desaturation was present. Goldmann perimetry showed a right enlarged blind spot with predominantly temporal visual field loss. Visually evoked potential (VEP) testing of the right eye showed slightly increased latency, but normal amplitude. Three weeks after discontinuation of the antiandrogen therapy, her symptoms resolved. Repeat Goldmann visual fields showed expansion. CONCLUSION Known side-effects of cyproterone acetate include retinal vascular disorder and retinal vein thrombosis, but an association with optic neuritis had not been described to date. There was a temporal relationship between cessation of the medication and improvement in visual symptoms. This implies that discontinuation of the offending drug constitutes the basis of treatment in drug-induced optic neuropathy.
-
8.
Cardiovascular Effects of Androgen Deprivation Therapy for the Treatment of Prostate Cancer: ABCDE Steps to Reduce Cardiovascular Disease in Patients With Prostate Cancer.
Bhatia, N, Santos, M, Jones, LW, Beckman, JA, Penson, DF, Morgans, AK, Moslehi, J
Circulation. 2016;(5):537-41
-
9.
Study Design and Rationale for the Phase 3 Clinical Development Program of Enobosarm, a Selective Androgen Receptor Modulator, for the Prevention and Treatment of Muscle Wasting in Cancer Patients (POWER Trials).
Crawford, J, Prado, CM, Johnston, MA, Gralla, RJ, Taylor, RP, Hancock, ML, Dalton, JT
Current oncology reports. 2016;(6):37
-
-
Free full text
-
Abstract
Muscle wasting in cancer is a common and often occult condition that can occur prior to overt signs of weight loss and before a clinical diagnosis of cachexia can be made. Muscle wasting in cancer is an important and independent predictor of progressive functional impairment, decreased quality of life, and increased mortality. Although several therapeutic agents are currently in development for the treatment of muscle wasting or cachexia in cancer, the majority of these agents do not directly inhibit muscle loss. Selective androgen receptor modulators (SARMs) have the potential to increase lean body mass (LBM) and hence muscle mass, without the untoward side effects seen with traditional anabolic agents. Enobosarm, a nonsteroidal SARM, is an agent in clinical development for prevention and treatment of muscle wasting in patients with cancer (POWER 1 and 2 trials). The POWER trials are two identically designed randomized, double-blind, placebo-controlled, multicenter, and multinational phase 3 trials to assess the efficacy of enobosarm for the prevention and treatment of muscle wasting in subjects initiating first-line chemotherapy for non-small-cell lung cancer (NSCLC). To assess enobosarm's effect on both prevention and treatment of muscle wasting, no minimum weight loss is required. These pivotal trials have pioneered the methodological and regulatory fields exploring a therapeutic agent for cancer-associated muscle wasting, a process hereby described. In each POWER trial, subjects will receive placebo (n = 150) or enobosarm 3 mg (n = 150) orally once daily for 147 days. Physical function, assessed as stair climb power (SCP), and LBM, assessed by dual-energy X-ray absorptiometry (DXA), are the co-primary efficacy endpoints in both trials assessed at day 84. Based on extensive feedback from the US Food and Drug Administration (FDA), the co-primary endpoints will be analyzed as a responder analysis. To be considered a physical function responder, a subject must have ≥10 % improvement in physical function compared to baseline. To meet the definition of response on LBM, a subject must have demonstrated no loss of LBM compared with baseline. Secondary endpoints include durability of response assessed at day 147 in those responding at day 84. A combined overall survival analysis for both studies is considered a key secondary safety endpoint. The POWER trials design was established with extensive clinical input and collaboration with regulatory agencies. The efficacy endpoints are a result of this feedback and discussion of the threshold for clinical benefit in patients at risk for muscle wasting. Full results from these studies will soon be published and will further guide the development of future anabolic trials. Clinical Trial ID: NCT01355484. https://clinicaltrials.gov/ct2/show/NCT01355484 , NCT01355497. https://clinicaltrials.gov/ct2/show/NCT01355497?term=g300505&rank=1 .
-
10.
Prevalence of osteoporosis in prostate cancer survivors II: a meta-analysis of men not on androgen deprivation therapy.
Lassemillante, AC, Doi, SA, Hooper, JD, Prins, JB, Wright, OR
Endocrine. 2015;(2):344-54
Abstract
The prevalence of osteoporosis in men with prostate cancer (PCa) on androgen deprivation therapy (ADT) is well documented, with up to 53% affected by this bone condition. However, there has been less emphasis on the burden of severe bone loss in men with PCa but not undergoing ADT. Therefore, the purpose of this meta-analysis is to compile evidence from the literature on the bone health of hormone-naïve PCa patients and to compare it to the bone health of men with PCa on ADT. Three databases were searched for the relevant literature published from 1990 until January 2014. The pooled prevalence of osteoporosis, low bone mass, and normal bone mass were estimated for this patient group and compared with similar subgroups from a previously published meta-analysis. The prevalence of osteoporosis varies from 4 to 38% in hormone-naïve PCa patients, and men with more advanced disease have a higher prevalence of osteoporosis. Men with PCa on ADT have poorer bone health than their hormone-naïve counterparts, but the trend toward poorer bone health with metastatic disease remains. In conclusion, it was found that men with PCa experience poor bone health prior to treatment with ADT. These results suggest that all men with PCa should have regular bone health monitoring, whether they commence ADT or not, in order to prevent or indeed minimize the morbidity that accompanies osteoporosis.