Patients Undergoing Androgen Deprivation Therapy Research Articles

Effects of a Combined Exercise and Dietary Intervention on Mobility Performance in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy

Effects of a Combined Exercise and Dietary Intervention on Mobility Performance in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy

Continuous release, solid depot, subcutaneous leuprolide acetate formulations to achieve and maintain castrate level serum testosterone levels below 20ng/dL in 4 open label, fixed dose studies.

e16062 Background: Growing evidence (eg, Klotz et al, EAU Congress 2014) suggest that prostate cancer patients undergoing androgen deprivation therapy who attained castrate levels of testosterone (...

Transcription of Nrdp1 by the androgen receptor is regulated by nuclear filamin A in prostate cancer.

Prostate cancer (PCa) progression is regulated by the androgen receptor (AR); however, patients undergoing androgen-deprivation therapy (ADT) for disseminated PCa eventually develop castration-resistant PCa (CRPC). Results of previous studies indicated that AR, a transcription factor, occupies distinct genomic loci in CRPC compared with hormone-naïve PCa; however, the cause of this distinction was unknown. The E3 ubiquitin ligase Nrdp1 is a model AR target modulated by androgens in hormone-naïve PCa but not in CRPC. Using Nrdp1, we investigated how AR switches transcription programs during CRPC progression. The proximal Nrdp1 promoter contains an androgen response element (ARE); we demonstrated AR binding to this ARE in androgen-sensitive PCa. Analysis of hormone-naive human prostatectomy specimens revealed correlation between Nrdp1 and AR expression, supporting AR regulation of NRDP1 levels in androgen-sensitive tissue. However, despite sustained AR levels, AR binding to the Nrdp1 promoter and Nrdp1 expression were suppressed in CRPC. Elucidation of the suppression mechanism demonstrated correlation of NRDP1 levels with nuclear localization of the scaffolding protein filamin A (FLNA) which, as we previously showed, is itself repressed following ADT in many CRPC tumors. Restoration of nuclear FLNA in CRPC stimulated AR binding to Nrdp1 ARE, increased its transcription, and augmented NRDP1 protein expression and responsiveness to ADT, indicating that nuclear FLNA controls AR-mediated androgen-sensitive Nrdp1 transcription. Expression of other AR-regulated genes lost in CRPC was also re-established by nuclear FLNA. Thus, our results indicate that nuclear FLNA promotes androgen-dependent AR-regulated transcription in PCa, while loss of nuclear FLNA in CRPC alters the AR-regulated transcription program.

A randomised controlled trial of a brief cognitive behavioural intervention for men who have hot flushes following prostate cancer treatment (MANCAN).

ObjectiveHot flushes and night sweats (HFNS) are experienced by up to 80% of prostate cancer patients undergoing androgen deprivation therapy (ADT). This study evaluates the effects of a guided self‐help cognitive behavioural therapy (CBT) intervention on HFNS problem‐rating (primary outcome), HFNS frequency, mood and health‐related quality of life (secondary outcomes) in patients undergoing ADT.MethodsPatients reporting treatment‐induced HFNS were randomly assigned to CBT (n = 33) or treatment as usual (TAU) (n = 35), stratified for cancer type. The CBT intervention included a booklet, CD plus telephone contact during a 4‐week period. Validated self‐report questionnaires were completed at baseline, 6 weeks and 32 weeks after randomisation. The primary outcome was HFNS problem rating (perceived burden of HFNS) at 6 weeks after randomisation. Potential moderators and mediators were examined. Data analysis was conducted on a modified intention‐to‐treat basis.ResultsCompared with TAU, CBT significantly reduced HFNS problem rating (adjusted mean difference: −1.33, 95% CI −2.07 to −0.58; p = 0.001) and HFNS frequency (−12.12, 95% CI −22.39 to −1.84; p = 0.02) at 6 weeks. Improvements were maintained at 32 weeks, but group differences did not reach significance. There were significant reductions in negative HFNS Beliefs and Behaviours following CBT, but not in mood or quality of life.ConclusionsGuided self‐help CBT appears to be a safe and effective brief treatment for men who have problematic HFNS following prostate cancer treatments. Further research might test the efficacy of the intervention in a multicentre trial. © 2015 The Authors. Psycho‐Oncology published by John Wiley & Sons Ltd.

The Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) in prostate cancer patients undergoing androgen deprivation therapy: study protocol for a randomized controlled trial.

BackgroundAndrogen deprivation therapy (ADT) is the foundation of treatment for men with metastatic prostate cancer and is now frequently incorporated into multimodality strategies for the curative treatment of locally advanced prostate cancer. Nevertheless, the catabolic effects of ADT result in meaningful adverse effects on physiological and quality of life outcomes, which may, in turn, increase the risk of functional decline, frailty, cardiovascular disease, and metabolic syndrome. Recent evidence demonstrates that lifestyle intervention promoting change in exercise and dietary behaviors is a promising approach, and may offset, or even reverse, the adverse effects accompanying ADT. Unfortunately, the limited existing studies of the effects of exercise and dietary interventions targeting patients with prostate cancer on ADT are characterized by high attrition rates and poor postintervention maintenance of treatment effects. Consequently, the Individualized Diet and Exercise Adherence Pilot Trial (IDEA-P) is designed to contrast the effects of a lifestyle intervention designed to promote independent self-management of exercise and dietary behavior with those of standard care disease management approach in the treatment of prostate cancer.Methods/DesignA total of 40 patients with prostate cancer undergoing ADT will be randomly assigned to lifestyle intervention or standard care. Outcomes of interest in IDEA-P include changes in self-reported and objectively assessed physical function and physical activity, dietary behavior, body composition, muscular strength, and quality of life. Outcomes will be obtained at baseline, 2-month, and 3-month assessments by trial personnel blinded to participants’ randomization assignment.DiscussionFindings from this study will establish the feasibility and preliminary efficacy of an innovative lifestyle intervention designed to promote progressively independent self-regulated exercise and dietary behavior change in the treatment of patients with prostate cancer undergoing ADT.Trial registrationClinicalTrials.gov NCT02050906.Electronic supplementary materialThe online version of this article (doi:10.1186/1745-6215-15-354) contains supplementary material, which is available to authorized users.

Circulating tumor cell count during zoledronic acid treatment in men with metastatic prostate cancer: a pilot study.

PurposeRecent clinical trials have demonstrated that zoledronic acid (ZOL) significantly prolongs survival in prostate cancer patients undergoing androgen deprivation therapy. This pilot study investigated the influence of ZOL on circulating tumor cell (CTC) counts in prostate cancer patients in association with prostate-specific antigen (PSA) used as a serum biomarker.MethodsPatients with metastatic castration-resistant prostate cancer (CRPC) who were CTC-positive (n=4) were enrolled in treatment with ZOL between April 2012 and December 2013. CTCs were detected using the Cell Search System. The study evaluated CTC fluctuations at 1, 2, and 3 months versus baseline, as well as patient outcomes and adverse events.ResultsTwo patients showed evidence of temporally decreased CTCs after ZOL treatment. Instead of decreasing the number of CTCs, the PSA level did not go down during the ZOL treatment. One patient could not undergo ZOL treatment due to rapid disease progression.ConclusionsAlthough CTC count arguably provides useful information about patients undergoing ZOL treatment, the positive influence of ZOL may be limited to temporary effects for CRPC.

Effects of exercise on disablement process model outcomes in prostate cancer patients undergoing androgen deprivation therapy.

Androgen-deprivation therapy (ADT) results in adverse physiologic, metabolic, and functional side effects that may accelerate functional limitations in patients with prostate cancer (PC). Although exercise improves muscular strength and functional performance, the extent to which exercise yields similar improvements in other disablement process outcomes in men on ADT has yet to be systematically evaluated. To explore whether exercise results in comparable improvements in physiologic and structural body system impairment, functional limitation (relating to basic physical or mental actions), and physical disability domain outcomes identifed in the Disablement Process Model (DPM) in PC patients who are receiving ADT. Data from studies of exercise interventions in men on ADT were extracted on impairment, functional limitation, and physical disability domain outcomes. The average of weighted, bias-corrected effect sizes were calculated for each outcome and compared across domains. A total of 9 studies (6 randomized controlled trials, 3 uncontrolled trials) conducted with 684 PC patients met the inclusion criteria. Exercise yielded heterogeneous effect-size improvements in physical impairments, ranging from large improvements in muscular strength (d = .74; 95% CI, .14-1.47) and endurance (d = 2.64; 95% CI, 1.08-2.84), to small improvements in body composition measures (d = .12; 95% CI, -.52-.68). Whereas exercise resulted in meaningful effect-size improvements in functional limitation domain outcomes (d = .39; 95% CI, -.42-1.01), fndings from the 4 studies that assessed a physical disability, domain outcomes revealed only small improvements (d = .10; 95% CI, -.44-.43) in these outcomes. Collectively, exercise consistently results in meaningful improvements in physical impairments and functional limitations in basic physical tasks. However, to date, few studies have evaluated the effects of exercise on physical disability domain outcomes, and the results suggest that the effects of exercise on physical disability measures are of a smaller magnitude relative to those observed for impairment and functional limitation domain outcomes.

Editorial Comment

The authors evaluated the risk for fracture because of the development of osteoporosis in men with prostate cancer who were subjected to androgen deprivation therapy (ADT) in the clinical scenario of prostate-specific antigen relapse after local therapy with curative intent, such as radical prostatectomy or radiation therapy. To assess the risk of fracture, the World Health Organization Fracture Risk Calculation Tool (FRAX) was applied, and the data obtained were compared with the results of the standard bone mineral density (BMD) evaluation by dual-energy X-ray absorptiometry (DXA) scans and the objective T scores derived from DXA scans. ADT is known as a significant contributor of osteoporosis in men with prostate cancer (PCa), and once diagnosed, osteoporosis needs to be treated by bone-targeting approaches, whereas osteopenia might be managed by preventive and supportive measures. Comparison of Fracture Risk Assessment Tool Score to Bone Mineral Density for Estimating Fracture Risk in Patients With Advanced Prostate Cancer on Androgen Deprivation TherapyUrologyVol. 84Issue 1PreviewTo estimate the risk of fracture (Fracture Risk Assessment Tool [FRAX] algorithm) because of the development of osteoporosis in prostate cancer patients undergoing androgen deprivation therapy (ADT) for patients who would otherwise not have been identified for treatment by the T score. Full-Text PDF

Comparison of Fracture Risk Assessment Tool Score to Bone Mineral Density for Estimating Fracture Risk in Patients With Advanced Prostate Cancer on Androgen Deprivation Therapy

To estimate the risk of fracture (Fracture Risk Assessment Tool [FRAX] algorithm) because of the development of osteoporosis in prostate cancer patients undergoing androgen deprivation therapy (ADT) for patients who would otherwise not have been identified for treatment by the T score. This study includes men undergoing ADT for prostate cancer at our urology group. Clinical data were collected via chart review. Subjects were evaluated for fracture risk using country specific (for the United States of America) World Health Organization's FRAX. The FRAX calculations were then compared to fracture risk as determined by T score, for a subset of our cohort that received dual-energy X-ray absorptiometry. Our cohort consisted of 613 patients on ADT, 94 of which had a dual-energy X-ray absorptiometry scan. The FRAX algorithm identified 61.6% patients requiring therapy without bone mass density (BMD), 46.8% with BMD, and 19.14% with T score alone. In addition, positive correlation was found between FRAX with and without BMD as well as T score and FRAX with BMD and without BMD. Our data indicate that many patients who were not found at significant risk for fracture with T score were in fact found to be at risk with the FRAX calculation. The largest proportion of patients was found to be at risk through the FRAX calculation without BMD, followed by FRAX with BMD, followed by T score alone. The utility of FRAX is beneficial in identifying patients that may benefit from effective bone-tropic treatment modalities.

Androgens alter T-cell immunity by inhibiting T-helper 1 differentiation.

The hormonal milieu influences immune tolerance and the immune response against viruses and cancer, but the direct effect of androgens on cellular immunity remains largely uncharacterized. We therefore sought to evaluate the effect of androgens on murine and human T cells in vivo and in vitro. We found that murine androgen deprivation in vivo elicited RNA expression patterns conducive to IFN signaling and T-cell differentiation. Interrogation of mechanism showed that testosterone regulates T-helper 1 (Th1) differentiation by inhibiting IL-12-induced Stat4 phosphorylation: in murine models, we determined that androgen receptor binds a conserved region within the phosphatase, Ptpn1, and consequent up-regulation of Ptpn1 then inhibits IL-12 signaling in CD4 T cells. The clinical relevance of this mechanism, whereby the androgen milieu modulates CD4 T-cell differentiation, was ascertained as we found that androgen deprivation reduced expression of Ptpn1 in CD4 cells from patients undergoing androgen deprivation therapy for prostate cancer. Our findings, which demonstrate a clinically relevant mechanism by which androgens inhibit Th1 differentiation of CD4 T cells, provide rationale for targeting androgens to enhance CD4-mediated immune responses in cancer or, conversely, for modulating androgens to mitigate CD4 responses in disorders of autoimmunity.

The FRAX score as a tool for estimating fracture risk in patients with advanced prostate cancer on androgen-deprivation therapy compared to the conventional T-score.

e16023Background: Prostate cancer (PCa) patients undergoing androgen deprivation therapy (ADT) are at increased risk of developing bone deficiency and associated morbidities due to hypogonadism-ind...

Defining a new testosterone threshold for medical castration: Results from a prospective cohort series.

We seek to determine if testosterone levels below the accepted castration threshold (50 ng/dL) have an impact on time to progression to castrate-resistant prostate cancer (CRPC). This is a prospective cohort series of patients undergoing androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone agonist or antagonist at a tertiary centre from 2006 to 2011. Serum testosterone level was assessed every 3 months. Patients with any testosterone >50 ng/dL were excluded. Patients were stratified into groups based on those achieving mean testosterone levels <20 ng/dL and <32 ng/dL. Progression to CRPC was assessed with the Kaplan-Meier method and compared with the log-rank test. A total of 32 patients were included in this study. Mean patient follow-up was 25.7 months. Patients with a 9-month serum testosterone <32 ng/dL had a significantly increased time to CRPC compared to patients with testosterone 32 to 50 ng/dL (p = 0.001, median progression-free survival (PFS) 33.1 months [<32 ng/dL] vs. 12.5 months [>32 ng/dL]). Patients with first year mean testosterone <32 ng/dL also had a significantly increased time to CRPC compared to 32 to 50 ng/dL (p = 0.05, median PFS 33.1 months [<32 ng/dL] vs. 12.5 months [32-50 ng/dL]). A testosterone <20 ng/dL compared to 20 to 50 ng/dL did not significantly predict with time to CRPC. This study supports a lower testosterone threshold to define optimal medical castration (T <32 ng/dL) than the previously accepted standard of 50 ng/dL. Testosterone levels during ADT serve as an early predictor of disease progression and thus should be measured in conjunction with prostate-specific antigen.

Abstract 5392: Metabolic profiling of castrate-resistant prostate cancer reveals novel role for bile acids in driving castration resistance.

Abstract The 5-year survival for metastatic castrate-resistant prostate cancer patients is less than 30% despite significant progress in the understanding of prostate cancer biology and development of novel therapeutic agents. A major contributing factor for the observed low survival rate of patients with castrate resistant disease is the lack of knowledge regarding metabolic alterations and their underlying contributions during development of castrate-resistant phenotype. Studies conducted in our laboratory and others identified a potential role for 2-methoxyestradiol (2-ME2) to prevent prostate cancer development and progression through inhibition of the anti-apoptotic protein FLIP. The goal of the current study was to identify biochemical changes in response to castration and treatment with 2-ME2 in serum from transgenic adenocarcinoma of mouse prostate (TRAMP) mice using mass spectrometry based global profiling. We identified a total of 54 biochemicals of which 16 increased and 38 decreased in castrated animals compared to sham-castration. Treatment of sham-castrated animals with low and high doses of 2-ME2 altered 91 and 145 biochemicals respectively. On the other hand treatment of castrated animals modulated 89 and 106 biochemicals. Cumulative analysis of these data also identified alteration of 60 biochemicals associated with castration effect, 149 with treatment and 70 interactions between castration and treatment effects. Castration affected metabolites involved in variety of metabolic pathways including lipid, oxidative stress, energetics and bile acid. Given the data showing enhanced expression of FLIP in castrate-resistant prostate tumors and upregulation of bile acids in patients undergoing androgen deprivation therapy, we examined the activation of FLIP in prostate cancer cells in response to deoxycholic acid (DCA). Our data suggests that transcriptional activity of FLIP was higher in PC-3 cells treated with DCA. To the best of our knowledge, this is the first report demonstrating global metabolomic profiling of serum in response to castration and provide a framework for therapeutic targeting of bile acid metabolism. Supported by NIH CA 135451 (APK). Citation Format: Divya Chakravarthy, Paul Rivas, Brian Keppler, Jianhua Ruan, Rita Ghosh, Addanki Pratap Kumar. Metabolic profiling of castrate-resistant prostate cancer reveals novel role for bile acids in driving castration resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5392. doi:10.1158/1538-7445.AM2013-5392 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

Androgen deprivation promotes intratumoral synthesis of dihydrotestosterone from androgen metabolites in prostate cancer

Intratumoral synthesis of dihydrotestosterone (DHT) from precursors cannot completely explain the castration resistance of prostate cancer. We showed that DHT was intratumorally synthesized from the inactive androgen metabolites 5α-androstane-3α/β,17β-diol (3α/β-diol) in prostate cancer cells via different pathways in a concentration-dependent manner. Additionally, long-term culture in androgen-deprived media increased transcriptomic expression of 17β-hydroxysteroid dehydrogenase type 6 (HSD17B6), a key enzyme of oxidative 3α-HSD that catalyzes the conversion of 3α-diol to DHT in prostate cancer cells. Correspondingly, the score for HSD17B6 in tissues of 42 prostate cancer patients undergoing androgen deprivation therapy (ADT) was about 2-fold higher than that in tissues of 100 untreated individuals. In men receiving ADT, patients showing biochemical progression had a higher HSD17B6 score than those without progression. These results suggested that 3α/β-diol also represent potential precursors of DHT, and the back conversion of DHT from androgen derivatives can be a promising target for combination hormone therapy.

A critical evaluation of body composition modalities used to assess adipose and skeletal muscle tissue in cancer

The majority of cancer patients experience some form of body composition change during the disease trajectory. For example, breast cancer patients undergoing chemotherapy and prostate cancer patients undergoing androgen deprivation therapy gain fat and lose skeletal muscle, which are associated with increased risk of cancer recurrence and clinical comorbidities. In contrast, advanced cancer patients, such as lung and colorectal cancer patients, experience symptoms of cancer cachexia (accelerated loss of skeletal muscle with or without adipose tissue loss), which are associated with decreased treatment response and poorer survival rates in advanced cancers. The heterogeneity of body composition features and their diverse implications across different cancer populations supports the need for accurate quantification of muscle and adipose tissue. Use of appropriate body composition modalities will facilitate an understanding of the complex relationship between body composition characteristics and clinical outcomes. This will ultimately support the development and evaluation of future therapeutic interventions that aim to counter muscle loss and fat gain in cancer populations. Despite the various metabolic complications that may confound the accurate body composition measurement in cancer patients (i.e., dehydration may confound lean tissue measurement), there are no guidelines for selecting the most appropriate modalities to make these measurements. In this review we outline specific considerations for choosing the most optimal approaches of lean and adipose tissue measurements among different cancer populations. Anthropometric measures, bioelectrical impedance analysis, air displacement plethysmography, dual-energy X-ray absorptiometry, computed tomography, and magnetic resonance imaging will be discussed.

Testosterone suppression: Impact of testosterone level on disease progression in advanced prostate cancer.

46 Background: In patients with advanced prostate cancer, medical castration remains a mainstay of treatment. A testosterone level below 50 ng/dL has been previously accepted as an adequate level of androgen suppression and remains the benchmark level for clinical trials. However, there is mounting evidence that lower testosterone levels may be associated with improved clinical outcomes. We evaluated our cohort of patients with advanced prostate cancer to assess the impact of testosterone suppression on progression to castrate resistant prostate cancer (CRPC). Methods: Patient data was obtained from a prospective database of patients undergoing androgen deprivation therapy (ADT) at a tertiary centre from 2006-2011. A total of 39 patients were eligible for inclusion with at least 12 months follow-up. Patients were administered LHRH agonists or antagonist with testosterone and PSA assessments every 3 months. Patients were considered to have progressed to CRPC when there were at least 2 consecutive rises in PSA above nadir, clinical progression, or death from disease. Patients were stratified into two risk groups based on 6-month absolute and 1-year mean testosterone levels following initiation of ADT. Baseline characteristics between risk groups were compared using the Student’s t-test and chi-squared test. Probability of disease progression was assessed using the Kaplan-Meier method and compared using the log-rank test. Results: Median patient follow up was 2.3 years with 38% free of disease at last follow up. Patients with 6-month absolute testosterone less than 32 ng/dL had an increased time to CRPC (log rank p=0.06). Patients with 1-year mean testosterone less than 32 ng/dl had a significantly increased time to CRPC (log rank p=0.005). Patients did not differ significantly in their baseline characteristics. Conclusions: Adequate testosterone suppression during ADT may play a clinically significant role in delaying CRPC. While PSA levels are often used to assess for response to ADT, the current study suggests testosterone level in the first year following initiation of ADT may serve as an early predictor of disease progression.

Circadian rhythm of hot flashes and activity levels among prostate cancer patients on androgen deprivation therapy

Objective. Altered circadian rhythms have been identified in untreated prostate cancer patients. Findings of restored rhythmicity following cancer treatment may have relevance for cancer control and symptom management. This study assessed and compared the cyclic patterns of hot flashes and activity levels in treated prostate cancer patients.Methods. Data were collected during two 24-h periods among 47 prostate patients undergoing androgen deprivation therapy (ADT). Hot flashes were detected objectively through sternal skin conductance and by patients via electronic event marking. Activity levels were recorded on a wrist actigraphy device.Results. The mean frequency of objectively measured and patient-reported hot flashes was 13.6 (SD = 14.3) and 12.6 (SD = 9.6), respectively. There were significant 24-h circadian rhythms of both hot flashes and activity levels. The peak of the rhythms occurred in early afternoon. There was no significant cross correlation between hot flashes and activity levels.Conclusions. The acrophases of hot flashes and elevated activity levels in this study may represent a normalisation of circadian rhythms following ADT, pointing to the need for more research, including controlled, prospective chronobiologic studies. Future research may have important implications for the survival of prostate cancer patients and the identification of new and safe hot flash treatments.

Activation of the Androgen Receptor by Intratumoral Bioconversion of Androstanediol to Dihydrotestosterone in Prostate Cancer

The androgen receptor (AR) mediates the growth of benign and malignant prostate in response to dihydrotestosterone (DHT). In patients undergoing androgen deprivation therapy for prostate cancer, AR drives prostate cancer growth despite low circulating levels of testicular androgen and normal levels of adrenal androgen. In this report, we demonstrate the extent of AR transactivation in the presence of 5α-androstane-3α,17β-diol (androstanediol) in prostate-derived cell lines parallels the bioconversion of androstanediol to DHT. AR transactivation in the presence of androstanediol in prostate cancer cell lines correlated mainly with mRNA and protein levels of 17β-hydroxysteroid dehydrogenase 6 (17β-HSD6), one of several enzymes required for the interconversion of androstanediol to DHT and the inactive metabolite androsterone. Levels of retinol dehydrogenase 5, and dehydrogenase/reductase short-chain dehydrogenase/reductase family member 9, which also convert androstanediol to DHT, were lower than 17β-HSD6 in prostate-derived cell lines and higher in the castration-recurrent human prostate cancer xenograft. Measurements of tissue androstanediol using mass spectrometry demonstrated androstanediol metabolism to DHT and androsterone. Administration of androstanediol dipropionate to castration-recurrent CWR22R tumor-bearing athymic castrated male mice produced a 28-fold increase in intratumoral DHT levels. AR transactivation in prostate cancer cells in the presence of androstanediol resulted from the cell-specific conversion of androstanediol to DHT, and androstanediol increased LAPC-4 cell growth. The ability to convert androstanediol to DHT provides a mechanism for optimal utilization of androgen precursors and catabolites for DHT synthesis.

Acupuncture for the Treatment of Hot Flashes in Men with Advanced Prostate Cancer

PURPOSE: To test the safety and efficacy of acupuncture in reducing hot flashes in men with advanced prostate cancer (CaP) undergoing androgen deprivation therapy. METHODS: A single-arm, pilot study was undertaken to evaluate acupuncture treatment for hot flashes experienced by CaP patients undergoing hormonal therapy. Sixteen advanced CaP patients undergoing androgen deprivation therapy (ADT) received standardized full body and auricular acupunc-ture 1x/week for 14 weeks. Patients were evaluated at 0, 7, 14, and an additional 14-wk follow-up (F/U) (28-wks). Safety was measured by monitoring for adverse events over the treatment period. Serum testosterone was measured at 0 and 14-wks. Quality of life (QOL) was measured by the hormone domain of the Expanded Prostate Index Composite (EPIC), at the 0, 7, 14, and 28-wks and patient reported hot flash frequency was assessed weekly. Safety endpoints were serum testosterone and analysis of adverse events. Efficacy endpoints were scores on the EPIC and the number of pa-tient reported hot flashes. RESULTS: 17 patients were enrolled and 15 completed the trial. Of 15 evaluable patients the median age was 68 ± 8.19. Serum analysis demonstrated no change in testosterone at baseline 9.5 ng/ml ± 8.9 vs. end-point 14 ± 8.78 (p = 0.101). No adverse events were reported. Data analysis of the EPIC demonstrated a trend toward improvement after 7 wks and a significant improvement following 14 wks of acupuncture (p = 0.01). Analysis of patient reported frequency showed a significant reduction in the number of hot flashes at 7-wk (6, p = 0.04), 14-wk (2.6, p = 0.001), and 28-wk F/U (3.2, p = 0.01) as compared to baseline 9.57 ± 3.98. CONCLUSIONS: The administration of acupuncture in men with advanced CaP appears to significantly decrease the frequency of hot flashes. No serious ad-verse events were noted and serum testosterone levels were unchanged from baseline suggesting that the mechanism of action of acupuncture for hot flash amelioration is not via increase in testosterone.

Gastrin‐releasing peptide: Predictor of castration‐resistant prostate cancer?

Neuroendocrine (NE) cells of the prostate are known to be androgen-independent and NE peptides like gastrin-releasing peptide (GRP) or neuron-specific enolase (NSE) can stimulate growth in a paracrine manner, and this is thought to be one of the escape mechanisms in castration-resistant prostate cancer (CRPCa). In a longitudinal study, we investigated the development of the NE serum factors GRP, NSE, and chromogranin A and their correlation with prostate-specific androgen (PSA) during hormonal treatment. Thirty two patients, with histology-proven, localized or metastatic prostatic carcinoma (PCa), who were undergoing therapy with LHRH analogue or a combination of LHRH analog and peripheral androgen blockade, took part in the study. In addition, eight healthy volunteers were each tested twice for serum GRP to elicit a "physiological" standard value. Blood samples were taken periodically from each patient within an 18-month time frame. We defined the standard value for GRP in the healthy participants as 0.852 ng/ml (mean + 2 SD) and observed that the GRP values for patients with PCa were significantly higher (P = 0.034). There was a positive correlation between PSA and GRP in patients with biochemical failure. CgA correlated with PSA development in the CRPCa patients. NSE values rose steadily over the study period, but with no correlation to PSA. Our data confirm that NE factors are elevated during hormonal treatment of prostate cancer. GRP is higher in PCa patients undergoing androgen deprivation therapy and is possibly involved in the initiation of hormonal escape in PCa.