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1.
BMJ ; 372: n37, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536184

RESUMO

OBJECTIVE: To assess the risk of meningioma associated with use of high dose cyproterone acetate, a progestogen indicated for clinical hyperandrogenism. DESIGN: Observational cohort study. SETTING: Data from SNDS, the French administrative healthcare database, between 2007 and 2015. PARTICIPANTS: 253 777 girls and women aged 7-70 years living in France who started cyproterone acetate between 2007 and 2014. Participants had at least one reimbursement for high dose cyproterone acetate and no history of meningioma or benign brain tumour, or long term disease status. Participants were considered to be exposed when they had received a cumulative dose of at least 3 g during the first six months (139 222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114 555 participants). 10 876 transgender participants (male to female) were included in an additional analysis. MAIN OUTCOME MEASURE: Surgery (resection or decompression) or radiotherapy for one or more intracranial meningiomas. RESULTS: Overall, 69 meningiomas in the exposed group (during 289 544 person years of follow-up) and 20 meningiomas in the control group (during 439 949 person years of follow-up) were treated by surgery or radiotherapy. The incidence of meningioma in the two groups was 23.8 and 4.5 per 100 000 person years, respectively (crude relative risk 5.2, 95% confidence interval 3.2 to 8.6; adjusted hazard ratio 6.6, 95% confidence interval 4.0 to 11.1). The adjusted hazard ratio for a cumulative dose of cyproterone acetate of more than 60 g was 21.7 (10.8 to 43.5). After discontinuation of cyproterone acetate for one year, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group. In a complementary analysis, 463 women with meningioma were observed among 123 997 already using cyproterone acetate in 2006 (risk of 383 per 100 000 person years in the group with the highest exposure in terms of cumulative dose). Meningiomas located in the anterior skull base and middle skull base, particularly the medial third of the middle skull base, involving the spheno-orbital region, appeared to be specific to cyproterone acetate. An additional analysis of transgender participants showed a high risk of meningioma (three per 14 460 person years; 20.7 per 100 000 person years). CONCLUSIONS: A strong dose-effect relation was observed between use of cyproterone acetate and risk of intracranial meningiomas. A noticeable reduction in risk was observed after discontinuation of treatment.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Acetato de Ciproterona/efeitos adversos , Neoplasias Meníngeas/induzido quimicamente , Meningioma/induzido quimicamente , Adolescente , Adulto , Idoso , Antagonistas de Androgênios/administração & dosagem , Estudos de Casos e Controles , Criança , Acetato de Ciproterona/administração & dosagem , Bases de Dados Factuais , Relação Dose-Resposta a Droga , Feminino , França/epidemiologia , Humanos , Incidência , Estudos Longitudinais , Neoplasias Meníngeas/epidemiologia , Meningioma/epidemiologia , Pessoa de Meia-Idade , Medição de Risco , Adulto Jovem
2.
J Urol ; 205(1): 60-67, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32856962

RESUMO

PURPOSE: Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMed® and Web of Science™ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the I2 statistic. We performed 6 meta-analyses for all cause dementia, Alzheimer disease and all cause dementia or Alzheimer disease according to the duration of androgen deprivation therapy (up to 12 or more than 12 months). RESULTS: A total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11-1.33 and HR 1.16, 95% CI 1.09-1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07-1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77-1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97-1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69-2.79 for exposure greater than 12 months). CONCLUSIONS: Men who receive androgen deprivation therapy for prostate cancer have an increased risk of dementia and/or Alzheimer disease compared to men who do not receive androgen deprivation therapy; this was more pronounced when androgen deprivation therapy was given longer than 12 months.


Assuntos
Doença de Alzheimer/epidemiologia , Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Demência/epidemiologia , Neoplasias da Próstata/tratamento farmacológico , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/prevenção & controle , Antagonistas de Androgênios/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Cognição/efeitos dos fármacos , Demência/induzido quimicamente , Demência/prevenção & controle , Esquema de Medicação , Humanos , Masculino , Neoplasias da Próstata/patologia , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Fatores de Tempo
3.
J Urol ; 205(1): 22-29, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32960678

RESUMO

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline discussing prognostic and treatment recommendations for patients with castration-resistant disease. Please refer to Part I for discussion of the management of patients with biochemical recurrence without metastatic disease after exhaustion of local treatment options as well as those with metastatic hormone-sensitive prostate cancer. RESULTS: The Advanced Prostate Cancer Panel created evidence- and consensus-based guideline statements to aid clinicians in the management of patients with advanced prostate cancer. Such statements are summarized in figure 1[Figure: see text] and detailed herein. MATERIALS AND METHODS: The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. A research librarian conducted searches in Ovid MEDLINE (1998 to January Week 5 2019), Cochrane Central Register of Controlled Trials (through December 2018), and Cochrane Database of Systematic Reviews (2005 through February 6, 2019). An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles. CONCLUSIONS: This guideline attempts to improve a clinician's ability to treat patients diagnosed with advanced prostate cancer. Continued research and publication of high-quality evidence from future trials will be essential to improve the level of care for these patients.


Assuntos
Oncologia/normas , Osteoporose/prevenção & controle , Fraturas por Osteoporose/prevenção & controle , Neoplasias de Próstata Resistentes à Castração/terapia , Urologia/normas , Técnicas de Ablação/métodos , Técnicas de Ablação/normas , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/normas , Consenso , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/normas , Humanos , Masculino , Oncologia/métodos , Gradação de Tumores , Estadiamento de Neoplasias , Osteoporose/diagnóstico , Osteoporose/etiologia , Fraturas por Osteoporose/etiologia , Prognóstico , Prostatectomia/normas , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/normas , Sociedades Médicas/normas , Resultado do Tratamento , Estados Unidos/epidemiologia , Urologia/métodos
4.
Cochrane Database Syst Rev ; 12: CD013245, 2020 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-33314020

RESUMO

BACKGROUND: Systemic androgen deprivation therapy (ADT), also referred to as hormone therapy,àhas long been the primary treatment for metastatic prostate cancer. Additional agents have been reserved for the castrate-resistant disease stage when ADT start becoming less effective. Abiraterone is an agent with an established role in that disease stage, which has only recently been evaluated in the hormone-sensitive setting. OBJECTIVES: To assess the effects of early abiraterone acetate, in combination with systemic ADT, for newly diagnosed metastatic hormone-sensitive prostate cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, six other databases, two trials registries, grey literature, and conference proceedings, up to 15 May 2020. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included randomized trials, in which men diagnosed with hormone-sensitive prostate cancer were administered abiraterone acetate and prednisolone with ADT or ADTàalone. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model. We rated the quality of evidence according to the GRADE approach. MAIN RESULTS: The search identified two randomized controlled trials (RCT), with 2201 men, who were assigned to receive either abiraterone acetate 1000 mg once daily and low dose prednisone (5mg) in addition to ADT, or ADT alone. In the LATITUDE trial, the median age and range of men in the intervention group was 68 (38 to 89) years, and 67 (33 to 92) years in the control group. Nearly all of the men in thisàstudy (97.6%) had prostate cancer with a Gleason score of at least 8 (ISUP grade group 4). Primary outcomes The addition of abiraterone acetate to ADT reduces the probability of death from any cause compared to ADT alone (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.56 to 0.73; 2 RCTs, 2201 men; high certainty of evidence); this corresponds to 163 fewer deaths per 1000 men with hormone-sensitive metastaticàprostate cancerà(210 fewer to 115 fewer) at five years. Abiraterone acetate in addition to ADT probably results in little to no differenceàin quality of life compared to ADT alone, measured with the Functional Assessment of Cancer Therapy-prostate total score (FACT-P; range 0 to 156; higher values indicates better quality of life),àat 12 months (mean difference [MD] 2.90 points, 95% CI 0.11 to 5.60; 1 RCT, 838 men; moderate certainty of evidence). Secondary outcomes Abiraterone plus ADT increases the risk of grades III to V adverse events compared to ADT alone (risk ratio [RR] 1.34, 95% CI 1.22 to 1.47; 1 RCT, 1199 men; high certainty of evidence); this corresponds to 162 more grade III to Vàevents per 1000 men with hormone-sensitive metastaticàprostate cancerà(105 more to 224 more) at a median follow-up of 30àmonths. Abiraterone acetate in addition to ADT probably reduces the probability of death due to prostate cancer compared to ADT alone (HR 0.58, 95% CI 0.50 to 0.68; 2 RCTs, 2201 men; moderate certainty of evidence). This corresponds to 120 fewer death from prostate cancer per 1000 men with hormone-sensitive metastaticàprostate cancerà(95% CI 145 fewer to 90 fewer) afteràa median follow-up of 30 months. The addition of abiraterone acetate to ADT probably decreases the probability of disease progression compared to ADT alone (HR 0.35, 95%CI 0.26 to 0.49; 2 RCTs, 2097 men; moderate certainty of evidence). This corresponds to 369 fewer incidences of disease progression per 1000 men with hormone-sensitive metastaticàprostate cancerà(456 fewer to 256 fewer)àafter a median follow-up of 30 months. The addition of abiraterone acetate to ADT probably increases the risk of discontinuing treatment due to adverse events compared to ADT alone (RR 1.50, 95% CI 1.17 to 1.92; 1 RCT, 1199 men; moderate certainty of evidence). This corresponds to 51 more men (95% CI 17 more to 93 more) discontinuing treatment because of adverse events per 1000 men treated with abiraterone acetate and ADT compared to ADT alone afteràa median follow-up of 30 months. AUTHORS' CONCLUSIONS: The addition of abiraterone acetate to androgen deprivation therapy improves overall survival but probably not quality of life. Itàprobably also extends disease-specific survival, and delays disease progression compared to androgen deprivation therapy alone. However, the risk of grades III to V adverse events is increased, and probably, so is the risk of discontinuing treatment due to adverse events.


Assuntos
Acetato de Abiraterona/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Acetato de Abiraterona/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Suspensão de Tratamento/estatística & dados numéricos
6.
BMJ ; 371: m3503, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028540

RESUMO

OBJECTIVE: To assess treatment related changes in quality of life up to 15 years after diagnosis of localised prostate cancer. DESIGN: Population based, prospective cohort study with follow-up over 15 years. SETTING: New South Wales, Australia. PARTICIPANTS: 1642 men with localised prostate cancer, aged less than 70, and 786 controls randomly recruited from the New South Wales electoral roll into the New South Wales Prostate Cancer Care and Outcomes Study (PCOS). MAIN OUTCOME MEASURES: General health and disease specific quality of life were self-reported at seven time points over a 15 year period, using the 12-item Short Form Health Survey scale, University of California, Los Angeles prostate cancer index, and expanded prostate cancer index composite short form (EPIC-26). Adjusted mean differences were calculated with controls as the comparison group. Clinical significance of adjusted mean differences was assessed by the minimally important difference, defined as one third of the standard deviation (SD) from the baseline score. RESULTS: At 15 years, all treatment groups reported high levels of erectile dysfunction, depending on treatment (62.3% (active surveillance/watchful waiting, n=33/53) to 83.0% (non-nerve sparing radical prostatectomy, n=117/141)) compared with controls (42.7% (n=44/103)). Men who had external beam radiation therapy or high dose rate brachytherapy or androgen deprivation therapy as primary treatment reported more bowel problems. Self-reported urinary incontinence was particularly prevalent and persistent for men who underwent surgery, and an increase in urinary bother was reported in the group receiving androgen deprivation therapy from 10 to 15 years (year 10: adjusted mean difference -5.3, 95% confidence interval -10.8 to 0.2; year 15: -15.9; -25.1 to -6.7). CONCLUSIONS: Patients receiving initial active treatment for localised prostate cancer had generally worse long term self-reported quality of life than men without a diagnosis of prostate cancer. Men treated with radical prostatectomy faired especially badly, particularly in relation to long term sexual outcomes. Clinicians and patients should consider these long term quality of life outcomes when making treatment decisions.


Assuntos
Antagonistas de Androgênios , Braquiterapia , Efeitos Adversos de Longa Duração , Prostatectomia , Neoplasias da Próstata , Qualidade de Vida , Idoso , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/uso terapêutico , Austrália/epidemiologia , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Estudos de Coortes , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Humanos , Efeitos Adversos de Longa Duração/epidemiologia , Efeitos Adversos de Longa Duração/etiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/psicologia , Neoplasias da Próstata/terapia , Risco Ajustado , Incontinência Urinária/epidemiologia , Incontinência Urinária/etiologia
7.
Lancet Oncol ; 21(11): 1513-1525, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32926841

RESUMO

BACKGROUND: In the CARD study, cabazitaxel significantly improved radiographic progression-free survival and overall survival versus abiraterone or enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel and the alternative androgen signalling-targeted inhibitor. Here, we report the quality-of-life outcomes from the CARD study. METHODS: CARD was a randomised, multicentre, open-label, phase 4 study involving 62 clinical sites across 13 European countries. Patients (aged ≥18 years, Eastern Cooperative Oncology Group (ECOG) performance status ≤2) with confirmed metastatic castration-resistant prostate cancer were randomly assigned (1:1) by means of an interactive voice-web response system to receive cabazitaxel (25 mg/m2 intravenously every 3 weeks, 10 mg daily prednisone, and granulocyte colony-stimulating factor) versus abiraterone (1000 mg orally once daily plus 5 mg prednisone twice daily) or enzalutamide (160 mg orally daily). Stratification factors were ECOG performance status, time to disease progression on the previous androgen signalling-targeted inhibitor, and timing of the previous androgen signalling-targeted inhibitor. The primary endpoint was radiographic progression-free survival; here, we present more detailed analyses of pain (assessed using item 3 on the Brief Pain Inventory-Short Form [BPI-SF]) and symptomatic skeletal events, alongside preplanned patient-reported outcomes, assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire and the EuroQoL-5 dimensions, 5 level scale (EQ-5D-5L). Efficacy analyses were done in the intention-to-treat population. Pain response was analysed in the intention-to-treat population with baseline and at least one post-baseline assessment of BPI-SF item 3, and patient-reported outcomes (PROs) were analysed in the intention-to-treat population with baseline and at least one post-baseline assessment of either FACT-P or EQ-5D-5L (PRO population). Analyses of skeletal-related events were also done in the intention-to-treat population. The CARD study is registered with ClinicalTrials.gov, NCT02485691, and is no longer enrolling. FINDINGS: Between Nov 17, 2015, and Nov 28, 2018, of 303 patients screened, 255 were randomly assigned to cabazitaxel (n=129) or abiraterone or enzalutamide (n=126). Median follow-up was 9·2 months (IQR 5·6-13·1). Pain response was observed in 51 (46%) of 111 patients with cabazitaxel and 21 (19%) of 109 patients with abiraterone or enzalutamide (p<0·0001). Median time to pain progression was not estimable (NE; 95% CI NE-NE) with cabazitaxel and 8·5 months (4·9-NE) with abiraterone or enzalutamide (hazard ratio [HR] 0·55, 95% CI 0·32-0·97; log-rank p=0·035). Median time to symptomatic skeletal events was NE (95% CI 20·0-NE) with cabazitaxel and 16·7 months (10·8-NE) with abiraterone or enzalutamide (HR 0·59, 95% CI 0·35-1·01; log-rank p=0·050). Median time to FACT-P total score deterioration was 14·8 months (95% CI 6·3-NE) with cabazitaxel and 8·9 months (6·3-NE) with abiraterone or enzalutamide (HR 0·72, 95% CI 0·44-1·20; log-rank p=0·21). There was a significant treatment effect seen in changes from baseline in EQ-5D-5L utility index score in favour of cabazitaxel over abiraterone or enzalutamide (p=0·030) but no difference between treatment groups for change from baseline in EQ-5D-5L visual analogue scale (p=0·060). INTERPRETATION: Since cabazitaxel improved pain response, time to pain progression, time to symptomatic skeletal events, and EQ-5D-5L utility index, clinicians and patients with metastatic castration-resistant prostate cancer can be reassured that cabazitaxel will not reduce quality of life when compared with treatment with a second androgen signalling-targeted inhibitor. FUNDING: Sanofi.


Assuntos
Androstenos/administração & dosagem , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/efeitos adversos , Androgênios/genética , Androstenos/efeitos adversos , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Feniltioidantoína/administração & dosagem , Feniltioidantoína/efeitos adversos , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Neoplasias de Próstata Resistentes à Castração/patologia , Qualidade de Vida , Taxoides/efeitos adversos , Resultado do Tratamento
10.
Biochim Biophys Acta Rev Cancer ; 1874(1): 188383, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32535158

RESUMO

Androgen deprivation therapy (ADT) is the primary systemic therapy for treating locally advanced or metastatic prostate cancer (PCa). Despite its positive effect on PCa patient survival, ADT causes various adverse effects, including increased cardiovascular risk factors and cardiotoxicity. Lifespans extension, early use of ADT, and second-line treatment with next-generation androgen receptor pathway inhibitors would further extend the duration of ADT and possibly increase the risk of ADT-induced cardiotoxicity. Meanwhile, information on the molecular mechanisms underlying ADT-induced cardiotoxicity and measures to prevent it is limited, mainly due to the lack of specifically designed preclinical studies and clinical trials. This review article compiles up-to-date evidence obtained from observational studies and clinical trials, in order to gain new insights for deciphering the association between ADT use and cardiotoxicity. In addition, potential cardioprotective strategies involving GnRH receptors and second messenger cGMP are discussed.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios/administração & dosagem , Androgênios/metabolismo , Antineoplásicos Hormonais/administração & dosagem , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/fisiopatologia , Cardiotoxicidade/prevenção & controle , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos como Assunto , GMP Cíclico/metabolismo , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Longevidade/fisiologia , Masculino , Estudos Observacionais como Assunto , Inibidores da Fosfodiesterase 5/farmacologia , Inibidores da Fosfodiesterase 5/uso terapêutico , Receptores LHRH/agonistas , Receptores LHRH/antagonistas & inibidores , Receptores LHRH/metabolismo , Fatores de Risco , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento
12.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 34-38, mar. 2020. tab
Artigo em Espanhol | LILACS | ID: biblio-1102292

RESUMO

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)


There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)


Assuntos
Humanos , Feminino , Idoso , Testosterona/uso terapêutico , Pós-Menopausa/efeitos dos fármacos , Depressores do Apetite/efeitos adversos , Fenitoína/efeitos adversos , Placebos/administração & dosagem , Psicotrópicos/efeitos adversos , Tamoxifeno/efeitos adversos , Testosterona/administração & dosagem , Testosterona/análise , Testosterona/efeitos adversos , Testosterona/farmacologia , Fármacos Cardiovasculares/efeitos adversos , Indometacina/efeitos adversos , Hormônio Liberador de Gonadotropina/efeitos adversos , Pós-Menopausa/fisiologia , Ensaios Clínicos Controlados como Assunto , Antagonistas Colinérgicos/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Danazol/efeitos adversos , Consenso , Inibidores da Aromatase/efeitos adversos , Uso Off-Label , Inibidores do Fator Xa/efeitos adversos , Anfetaminas/efeitos adversos , Antagonistas dos Receptores Histamínicos/efeitos adversos , Antagonistas de Androgênios/efeitos adversos , Androgênios/fisiologia , Cetoconazol/efeitos adversos , Entorpecentes/efeitos adversos
13.
Int J Radiat Oncol Biol Phys ; 106(5): 939-947, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32029346

RESUMO

PURPOSE: Cabazitaxel has been demonstrated to improve the overall survival for men with metastatic castrate-resistant prostate cancer. The purpose of this study was to determine the maximum tolerated dose for concurrent cabazitaxel with androgen deprivation and intensity modulated radiation therapy in men with high-risk prostate cancer. METHODS AND MATERIALS: Twenty men were enrolled in this institutuional review board-approved phase I clinical trial using a 3 + 3 design. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition. RESULTS: With a median follow-up time of 56 months, the maximum tolerated dose of concurrent cabazitaxel was 6 mg/m2. The 5-year biochemical disease-free survival was 73%, despite 75% of patients having very high risk prostate cancer per the National Comprehensive Cancer Network guidelines. Four patients were unable to complete chemotherapy owing to dose-limiting toxicities (eg, rectal bleeding, diarrhea, and elevated transaminase). There was no significant minimally important difference in Expanded Prostate Index Composite patient-reported outcomes for either the urinary or bowel domains; however, there was a significant decrease in the sexual domain. CONCLUSIONS: This is the first clinical trial of prostate cancer to report on the combination of cabazitaxel and radiation therapy. The maximum tolerated dose of concurrent cabazitaxel with radiation and androgen deprivation therapy was determined to be 6 mg/m2. Despite the aggressive nature of the disease, robust biochemical control was observed.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Radioterapia de Intensidade Modulada , Taxoides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Terapia Combinada , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/patologia , Qualidade da Assistência à Saúde , Radioterapia de Intensidade Modulada/efeitos adversos , Segurança , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento
14.
Medicine (Baltimore) ; 99(7): e18842, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049786

RESUMO

Acute urinary retention (AUR) is associated with hormone imbalance in men. However, limited studies focused on exploring the complications of AUR in patients with prostate cancer (PC) who receive androgen deprivation therapy (ADT). Therefore, we aim to evaluate the subsequent risk of AUR in ADT-treated PC patients. We collected data from 24,464 male patients who were newly diagnosed with prostate malignancy from a longitudinal health insurance database of catastrophic illness in 2000 to 2008. All PC patients were categorized into 2 cohorts, namely, ADT cohort and non-ADT cohort, based on whether or not the patient receives ADT. The patients were followed up until the occurrence of AUR. Multivariate Cox proportional hazard regression and Kaplan-Meier analysis were performed. After a 12-year follow-up, the incidence rates of AUR were 12.49 and 9.86 per 1000 person-years in ADT and non-ADT cohorts, respectively. Compared with the non-ADT cohort, the ADT cohort had a 1.21-fold increase in AUR risk based on the adjusted model (95% CI = 1.03-1.43). In addition, PC patients receiving early ADT treatment within 6 months or receiving only luteinizing hormone-releasing hormone treatment also had significantly increased risk of AUR. ADT was positively associated with AUR risk. PC patients receiving ADT should be informed about the risks of bladder outlet obstruction and AUR, and they may benefit from screening for related risk factors. New guidelines and treatments should be proposed in the future to manage ADT-related lower urinary tract symptoms and reduce the risk of AUR.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Retenção Urinária/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Estudos de Casos e Controles , Humanos , Incidência , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taiwan/epidemiologia , Retenção Urinária/induzido quimicamente
15.
PLoS One ; 15(2): e0229263, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32074125

RESUMO

PURPOSE: This study aimed to investigate the association between androgen deprivation therapy (ADT) and the risk of subsequently developing hematologic disorders in patients with prostate cancer. MATERIALS AND METHODS: This population-based nationwide cohort study utilized data from the Taiwan National Health Insurance Research Database between 1997 and 2013. The patients were divided into three groups-those who received ADT only (ADT-only group), those who had radiotherapy (RT) only (RT-only group), and those treated with radical prostatectomy (RP) only (RP-only group). The study outcome was newly diagnosed hematologic disorder, including anemia and hematologic malignancy. Propensity score-matched, Cox regression, and Kaplan-Meier curve analyses were performed to investigate the risk of subsequently developing hematologic disorders after ADT. RESULTS: Of the 17,168 patients with prostate cancer who were included in the study, 13,318 met the inclusion and exclusion criteria. After propensity score matching, 1,797, 1,797, and 1,797 patients treated with ADT only, RT only, and RP only, respectively, who had a median follow-up period of 4.32 years were included in the study cohort. Compared with the patients treated with RP only, those who received ADT and RT were significantly at increased risk of subsequently developing hematologic disorders (ADT: adjusted hazard ratio [aHR]: 1.60, 95% confidence interval [CI]: 1.29-1.97; RT: aHR, 1.98, 95% CI: 1.62-2.42) according to the Cox regression analysis. Based on the Kaplan-Meier curve analysis, patients with bone metastasis who received ADT only had the lowest cumulative probabilities of not developing hematologic disorders. Moreover, a significantly increased risk of hematologic disorders was observed with the increasing duration of ADT (P for trend < .001). CONCLUSIONS: The use of ADT in patients with prostate cancer may increase the risk of subsequently developing hematologic disorders.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Doenças Hematológicas/induzido quimicamente , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/secundário , Estudos de Coortes , Seguimentos , Doenças Hematológicas/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/patologia , Fatores de Risco , Taxa de Sobrevida , Taiwan/epidemiologia
16.
Cancer Epidemiol ; 64: 101657, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31918180

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) remains the mainstay treatment for locally advanced or metastatic prostate cancer (PC). However, potential effects of ADT treatment on neurocognitive dysfunction remain unclear. The present study was conducted to assess the relation between ADT treatment and risk of cognitive decline in Asian men with PC. METHODS: A population-based cohort of 24,464 men with PC, each newly diagnosed between 2000 and 2008, was selected from the Taiwan National Health Insurance Database. Subjects were further grouped by treatment as non-ADT (n = 4685) or ADT (n = 12,740), members of the latter subjected to bilateral orchiectomy or medical treatment (ie, luteinizing hormone-releasing hormone agonists, antiandrogens, or combination therapy). A multivariable Cox proportional hazard model with ADT as time-dependent covariate was used to generate adjusted hazard ratios (HRs) of subsequent cognitive decline, including dementia, Alzheimer's disease (AD), and Parkinson's disease (PD). RESULTS: ADT showed a significant association with overall risk of cognitive decline (HR = 1.51, 95 % CI: 1.31-1.74), especially for PD, dementia, and non-Alzheimer dementia (non-AZD). When stratified by various ADT regimens, antiandrogen-only recipients displayed significantly heightened risks of subsequent AD, non-AZD, and PD. However, combined androgen blockade also imposed an increased risk of PD. There was no apparent correlation between duration of ADT exposure and cognitive dysfunction. CONCLUSIONS: Various ADT therapies may have disparate impacts on cognitive function. Prospective studies exploring pertinent clinical characteristics more fully are needed to confirm these findings.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Disfunção Cognitiva/epidemiologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Cognição/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/etiologia , Estudos de Coortes , Terapia Combinada , Bases de Dados Factuais , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Masculino , Pessoa de Meia-Idade , Orquiectomia/efeitos adversos , Orquiectomia/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Taiwan/epidemiologia
17.
JAMA ; 323(2): 149-163, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935027

RESUMO

Importance: Understanding adverse effects of contemporary treatment approaches for men with favorable-risk and unfavorable-risk localized prostate cancer could inform treatment selection. Objective: To compare functional outcomes associated with prostate cancer treatments over 5 years after treatment. Design, Setting, and Participants: Prospective, population-based cohort study of 1386 men with favorable-risk (clinical stage cT1 to cT2bN0M0, prostate-specific antigen [PSA] ≤20 ng/mL, and Grade Group 1-2) prostate cancer and 619 men with unfavorable-risk (clinical stage cT2cN0M0, PSA of 20-50 ng/mL, or Grade Group 3-5) prostate cancer diagnosed in 2011 through 2012, accrued from 5 Surveillance, Epidemiology and End Results Program sites and a US prostate cancer registry, with surveys through September 2017. Exposures: Treatment with active surveillance (n = 363), nerve-sparing prostatectomy (n = 675), external beam radiation therapy (EBRT; n = 261), or low-dose-rate brachytherapy (n = 87) for men with favorable-risk disease and treatment with prostatectomy (n = 402) or EBRT with androgen deprivation therapy (n = 217) for men with unfavorable-risk disease. Main Outcomes and Measures: Patient-reported function, based on the 26-item Expanded Prostate Index Composite (range, 0-100), 5 years after treatment. Regression models were adjusted for baseline function and patient and tumor characteristics. Minimum clinically important difference was 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritative symptoms, and 4 to 6 for bowel and hormonal function. Results: A total of 2005 men met inclusion criteria and completed the baseline and at least 1 postbaseline survey (median [interquartile range] age, 64 [59-70] years; 1529 of 1993 participants [77%] were non-Hispanic white). For men with favorable-risk prostate cancer, nerve-sparing prostatectomy was associated with worse urinary incontinence at 5 years (adjusted mean difference, -10.9 [95% CI, -14.2 to -7.6]) and sexual function at 3 years (adjusted mean difference, -15.2 [95% CI, -18.8 to -11.5]) compared with active surveillance. Low-dose-rate brachytherapy was associated with worse urinary irritative (adjusted mean difference, -7.0 [95% CI, -10.1 to -3.9]), sexual (adjusted mean difference, -10.1 [95% CI, -14.6 to -5.7]), and bowel (adjusted mean difference, -5.0 [95% CI, -7.6 to -2.4]) function at 1 year compared with active surveillance. EBRT was associated with urinary, sexual, and bowel function changes not clinically different from active surveillance at any time point through 5 years. For men with unfavorable-risk disease, EBRT with ADT was associated with lower hormonal function at 6 months (adjusted mean difference, -5.3 [95% CI, -8.2 to -2.4]) and bowel function at 1 year (adjusted mean difference, -4.1 [95% CI, -6.3 to -1.9]), but better sexual function at 5 years (adjusted mean difference, 12.5 [95% CI, 6.2-18.7]) and incontinence at each time point through 5 years (adjusted mean difference, 23.2 [95% CI, 17.7-28.7]), than prostatectomy. Conclusions and Relevance: In this cohort of men with localized prostate cancer, most functional differences associated with contemporary management options attenuated by 5 years. However, men undergoing prostatectomy reported clinically meaningful worse incontinence through 5 years compared with all other options, and men undergoing prostatectomy for unfavorable-risk disease reported worse sexual function at 5 years compared with men who underwent EBRT with ADT.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Braquiterapia/efeitos adversos , Medidas de Resultados Relatados pelo Paciente , Prostatectomia/efeitos adversos , Neoplasias da Próstata/terapia , Radioterapia/efeitos adversos , Idoso , Antagonistas de Androgênios/uso terapêutico , Terapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Radioterapia/métodos , Disfunções Sexuais Fisiológicas/etiologia , Resultado do Tratamento , Incontinência Urinária/etiologia , Conduta Expectante
18.
Future Oncol ; 16(6): 147-149, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31964195

RESUMO

The Open University's first one-day symposium on treatment-emergent neuroendocrine prostate cancer attracted world-leading figures, early career researchers and industry colleagues. The symposium proved insightful into the 'real-world' impact and current problems faced in the diagnosis and treatment of neuroendocrine prostate cancer. It was important for this meeting to take place as the incidence of neuroendocrine prostate cancer is increasing due to the widespread use of next-generation androgen deprivation drugs. The symposium discussions proposed new molecularly driven deadlines to accelerate research and improved the treatment of this deadly and poorly recognized malignancy.


Assuntos
Tumores Neuroendócrinos/terapia , Neoplasias de Próstata Resistentes à Castração/terapia , Antagonistas de Androgênios/efeitos adversos , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Humanos , Masculino , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/imunologia , Tumores Neuroendócrinos/patologia , Guias de Prática Clínica como Assunto , Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/imunologia , Neoplasias de Próstata Resistentes à Castração/patologia , Microambiente Tumoral/imunologia
19.
Arterioscler Thromb Vasc Biol ; 40(3): e55-e64, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31969015

RESUMO

Androgen deprivation therapy is a cornerstone of prostate cancer treatment. Pharmacological androgen deprivation includes gonadotropin-releasing hormone agonism and antagonism, androgen receptor inhibition, and CYP17 (cytochrome P450 17A1) inhibition. Studies in the past decade have raised concerns about the potential for androgen deprivation therapy to increase the risk of adverse cardiovascular events such as myocardial infarction, stroke, and cardiovascular mortality, possibly by exacerbating cardiovascular risk factors. In this review, we summarize existing data on the cardiovascular effects of androgen deprivation therapy. Among the therapies, abiraterone stands out for increasing risk of cardiac events in meta-analyses of both randomized controlled trials and observational studies. We find a divergence between observational studies, which show consistent positive associations between androgen deprivation therapy use and cardiovascular disease, and randomized controlled trials, which do not show these associations reproducibly.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Sistema Cardiovascular/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Cardiotoxicidade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/terapia , Sistema Cardiovascular/fisiopatologia , Humanos , Masculino , Medição de Risco , Fatores de Risco , Resultado do Tratamento
20.
Int J Mol Med ; 45(2): 485-496, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894256

RESUMO

Combined androgen deprivation therapy (ADT) and radiation therapy (RT) is the standard of care treatment for non­metastatic prostate cancer (NMPC). Despite the efficacy, treatment­related symptoms including fatigue greatly reduce the quality of life of cancer patients. The goal of the study is to examine the influence of combined ADT/RT on fatigue and understand its underlying mechanisms. A total of 64 participants with NMPC were enrolled. Fatigue was assessed using the Functional Assessment of Cancer Therapy­Fatigue. Mitochondrial function parameters were measured as oxygen consumption from peripheral blood mononuclear cells (PBMCs) extracted from participants' whole blood. An ADT/RT­induced fatigue mouse model was developed, with fatigue measured as a reduction in voluntary wheel­running activity (VWRA) in 54 mice. Mitochondrial function was assessed in the ADT/RT mouse brains using western blot analysis of glucose transporter 4 (GLUT4) and transcription factor A, mitochondrial (TFAM). The results demonstrated that fatigue in the ADT group was exacerbated during RT compared with the non­ADT group. This effect was specific to fatigue, as depressive symptoms were unaffected. PBMCs of fatigued subjects exhibited decreased ATP coupling efficiency compared to non­fatigued subjects, indicative of mitochondrial dysfunction. The ADT/RT mice demonstrated the synergistic effect of ADT and RT in decreasing VWRA. Brain tissues of ADT/RT mice exhibited decreased levels of GLUT4 and TFAM suggesting that impaired neuronal metabolic homeostasis may contribute to fatigue pathogenesis. In conclusion, these findings suggest that fatigue induced by ADT/RT may be attributable to mitochondrial dysfunction both peripherally and in the central nervous system (CNS). The synergistic effect of ADT/RT is behaviorally reproducible in a mouse model and its mechanism may be related to bioenergetics in the CNS.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Fadiga/etiologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Idoso , Antagonistas de Androgênios/efeitos adversos , Animais , Terapia Combinada/efeitos adversos , Fadiga/patologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Mitocôndrias/efeitos da radiação , Neoplasias da Próstata/complicações , Neoplasias da Próstata/patologia , Qualidade de Vida
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