Locally advanced and metastatic prostate cancer treated with intermittent androgen monotherapy or maximal androgen blockade : results from a randomised phase 3 study by the South European uroncological group

Background: Few randomised studieshave compared antiandrogen intermittent hormonal therapy (IHT) with continuousmaximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa). Objective: To determine whetheroverall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS oncontinuous MAB. Design, setting, and participants:This phase 3 randomised trial compared IHT and continuous MAB in patients withlocally advanced or metastatic PCa. Intervention: During induction,patients received CPA 200 mg/d for 2 wk and then monthly depot injections of aluteinising hormone-releasing hormone (LHRH; triptoreline 11.25 mg) analogueplus CPA 200 mg/d. Patients whose prostate-specific antigen (PSA) was 5 yr, respectively,after randomisation. The main limitation is that the length of time for thetrial to mature means that other therapies are now available. A secondlimitation is that T3 patients may now profit from watchful waiting instead ofandrogen-deprivation therapy. Conclusions: Noninferiority of IHTin terms of survival and its association with better sexual activity thancontinuous therapy suggest that IHT should be considered for use in routineclinical practice

Is intermittent androgen-deprivation therapy beneficial for patients with advanced prostate cancer?

Use of intermittent androgen-deprivation therapy (IADT) in patients with prostate cancer has been evaluated in several studies, in an attempt to delay the development of castration resistance and reduce side-effects associated with ADT. However it is still not clear whether survival is adversely affected in patients treated with IADT. In this review, we explore the available data in an attempt to identify the most suitable candidate patients for IADT, and discuss factors that may inform appropriate patient stratification. ADT is first-line treatment for advanced/metastatic prostate cancer and is also recommended for use with definitive radiotherapy for high-risk localised prostate cancer. The changes in hormone levels induced by ADT can lead to short-and long-term side-effects which, although treatable in most cases, can significantly reduce the tolerability of ADT treatment. IADT has been investigated in several phase II and phase III studies in patients with locally advanced or metastatic prostate cancer, in an attempt to delay time to tumour progression and reduce the side-effect burden of ADT. In selected patient groups IADT is no less effective than continuous ADT, ameliorating the impact of ADT-related side-effects, and, to a degree, their impact on patient health-related quality of life (HRQL). Further comparative study is required, particularly in relation to HRQL and long-term complications associated with ADT

Intermittent androgen deprivation for locally advanced and metastatic prostate cancer : results from a randomised phase III study of the South European Uroncological group

Background: Few randomised studies have compared intermittent hormonal therapy with continuous therapy for the treatment of advanced prostate cancer Objective: To determine if intermittent therapy is associated with a shorter time to progression. Design Setting and participants: 766 patients with locally advanced or metastatic prostate cancer received a three month induction treatment. 626 patients whose PSA decreased below 4 ng/ml or to 80% below the initial value, were randomised. Intervention: Patients received cyproterone acetate (CPA) 200 mg for two weeks and then monthly depot injections of a LHRH analogue plus 200 mg of CPA daily during induction. Patients randomised to the intermittent arm ceased treatment while those randomised to the continuous arm received 200 mg of CPA daily plus a LHRH analogue. Measurements. Primary outcome was time to subjective or objective progression. Secondary outcomes were survival and quality of life. Time off therapy in the intermittent arm was also recorded. Results and Limitations: 127 intermittent and 107 continuous patients progressed with hazard ratio 0.81 (95% CI 0.63 to 1.05), p=0.11. There was no difference in survival, with hazard ratio 0.99 (95% CI 0.80 to 1.23) and 170 deaths on the intermittent and 169 on the continuous arm. A slight excess of cancer deaths in the intermittent treatment arm (106 versus 84) is balanced by a slight excess of cardiovascular deaths in the continuous arm (52 versus 41). Side effects are more pronounced on the continuous arm. Men treated with intermittent therapy reported better sexual function. Median time off therapy for the intermittent patients was 52 weeks (95% CI 39.4, 65.7). Conclusion: Intermittent therapy should be considered for use in routine practice since it is associated with no reduction in survival, no clinically meaningful impairment in quality of life, better sexual activity, and considerable economic benefit to individual and community

Androgen deprivation therapy in castrate-resistant prostate cancer: how important is GnRH agonist backbone therapy?

Background: A growing number of treatment options exist to treat metastatic castrate-resistant prostate cancer (mCRPC), and with these newer options, many questions about optimising treatment remain unanswered. One recommendation that may potentially be overlooked by practitioners is that androgen deprivation therapy (ADT) should be maintained when CRPC develops and when treatment with any of the newer agents is initiated. Aim: However, to emphasise this recommendation, it is valuable to interrogate the evidence for maintaining ADT in different clinical situations. Outcome: This statement, reflecting the views of the authors, provides a discussion of this evidence and the rationale behind the recommendation that ADT should be continued in CRPC.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Sequential Intravesical Chemoimmunotherapy with Mitomycin C and Bacillus Calmette-Guerin and with Bacillus Calmette-Guerin Alone in Patients with Carcinoma in Situ of the Urinary Bladder: Results of an EORTC Genito-Urinary Group Randomized Phase 2 Trial (30993)

Background: Bacillus Calmette-Guerin (BCG) is the intravesical treatment of choice for carcinoma in situ (CIS)

Intermittent Androgen-deprivation Therapy in Prostate Cancer: A Critical Review Focused on Phase 3 Trials

Context: Intermittent androgen deprivation (IAD) in prostate cancer (PCa) patients has been proposed to delay development of castration resistance and to reduce the side effects and costs of androgen deprivation therapy (ADT). Objective: This review analyzes (1) the oncologic and quality of life (QoL) results from randomized phase 3 trials comparing IAD and continuous ADT and (2) the prognostic parameters for IAD. Evidence acquisition: We searched the Medline and Cochrane Library databases (primary fields: prostate neoplasm and intermittent androgen deprivation; secondary fields: randomized trials, survival, quality of life, predictors) without language restriction. Evidence synthesis: We found seven extensively described phase 3 trials randomizing 4675 patients to IAD versus continuous ADT. Other randomized trials investigating IAD have been performed, but available data are limited and have been published only in preliminary fashion. In all seven trials, patients spent most of their time on, rather than off, ADT. The induction periods ranged from 3 mo to 8 mo; in all but one trial, the PSA level designated for ADT discontinuation was <4 ng/ml. Mean follow-up ranged from 40-108 mo. Collectively, these trials support the concept that, mainly in metastatic cases, IAD can produce oncologic results similar to continuous ADT. In terms of overall survival, the hazard ratios for IAD and continuous ADT were very similar (range: 0.98-1.08). The QoL benefit of IAD appears to be modest at best. With IAD, QoL is likely influenced by the duration of the off-treatment periods and by the rate of testosterone recovery. Conclusions: The evidence indicates that IAD is not inferior to continuous ADT. Data are insufficient to determine whether IAD is able to prevent the long-term complications of ADT. More comparative analysis focused on QoL is warranted. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved

A Gencitabina como Alternativa Terapêutica na Ausência de BCG: A Experiência do CHLC (Hospital S. José)

Introduction: The non-muscle invasive bladder tumors should be stratified into risk groups so the adjuvant treatment after surgery can be suited to each patient. The high risk tumors should be treated with one to three-year maintenance intravesical bacillus Calmette-Guérin (BCG). It has been reported shortages of intravesical BCG and our hospital center was affected in 2014/2015, leading to a treatment change of the patients who had indication to BCG. Gemcitabine could be a valid alternative because some studies show it may have a role in intermediate-risk patients, as an alternative to mitomycin C, and in high risk, BCG-refractory patients, with a better toxicity profile. Material and Methods: This is a descriptive, retrospective study that included patients with non-muscle invasive bladder tumors of high risk with onset of disease in 2013/2014, affected by the BCG shortage period at the Hospital Center. Results: At CHLC, 11 high-risk patients were treated with gemcitabine, only two exclusively, and the others sequentially with BCG. Only two patients, treated with both gemcitabine and BCG, had tumoral recurrence. However, a significant number (6 out of 11) had adverse events, two of whom had to stop treatment. Conclusion: Apparently, gemcitabine seems to be a good adjuvant treatment choice during the shortage of the gold standard treatment, due to the low number of recurrence, although adverse events reported were high.Introdução: Os tumores não músculo invasivos da bexiga devem ser estratificados em grupos de risco de forma a adequar o tratamento após cirurgia a cada doente. Nos tumores de alto risco deve ser realizada terapêutica adjuvante com bacilo de Calmette-Guérin (BCG) intravesical durante 1 a 3 anos. Têm sido reportadas roturas de stock de BCG intravesical, tendo sido o Centro Hospitalar de Lisboa Central (CHLC) afectado nos anos 2014 e 2015, o que obrigou a uma reformulação no tratamento dos doentes que tinham indicação para realização desta terapêutica. A gencitabina poderá ser uma alternativa válida, dado que alguns estudos mostram que poderá ter um papel nos doentes de risco intermédio, como alternativa à mitomicina C, e nos de alto risco, refractários à BCG, com um perfil de toxicidade mais favorável. Material e Métodos: Trata-se de um estudo retrospectivo descritivo que incluiu doentes com tumores da bexiga não musculo-invasivos de alto risco, com início da doença em 2013/2014, afectados pelo período de escassez de BCG no Centro Hospitalar. Resultados: No CHLC, 11 doentes com tumores de alto risco foram submetidos a terapêutica com gencitabina, apenas dois exclusivamente, os restantes sequencialmente com BCG. Apenas dois doentes, tratados com BCG e gencitabina, apresentaram recidiva tumoral. No entanto, um número significativo (6 em 11) sofreram efeitos adversos, dois dos quais que levaram à interrupção da terapêutica. Conclusão: Aparentemente, a gencitabina foi uma boa alternativa de terapêutica adjuvante na ausência do tratamento gold standard (BCG), dada a existência de baixo número de recidivais tumorais, apesar do elevado número de efeitos adversos reportados