Continuous versus Six Months a Year Maximal Androgen Blockade in the Management of Prostate Cancer: A Randomised Study

Irani, Jacques; Celhay, O.; Hubert, Jacques; Bladou, Franck; Ragni, E.; Trape, Gérard; Doré, B.

doi:10.1016/j.eururo.2008.02.024

Cited by 34 publications

(27 citation statements)

References 19 publications

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“…During follow-up, although progressively more patients in the intermittent arm were on therapy and sexual activity decreased, sexual activity was still significantly higher than among patients on continuous therapy. Similar results have been reported in SEUG 9401 [2] and in other studies [6,[13][14][15]. In protocol S9346 from Hussein et al [3], IADT was proven to be noninferior to continuous deprivation in patients with extensive disease; however, intermittent therapy was statistically inferior in patients with minimal disease, suggesting that continuous therapy would be the preferred treatment in this group.…”

Section: Discussionsupporting

confidence: 74%

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

Silva

Gonçalves

et al. 2014

European Urology

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a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m Article info AbstractBackground: Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa). Objective: To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB. Design, setting, and participants: This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa. Intervention: During induction, patients received CPA 200 mg/d for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH; triptoreline 11.25 mg) analogue plus CPA 200 mg/d. Patients whose prostate-specific antigen (PSA) was <4 ng/ml after 3 mo of induction treatment were randomised to the IHT arm (stopped treatment and restarted on CPA 300 mg/d monotherapy if PSA rose to 20 ng/ml or they were symptomatic) or the continuous arm (CPA 200 mg/d plus monthly LHRH analogue). Outcome measurements and statistical analysis: Primary outcome measurement was OS. Secondary outcomes included cause-specific survival, time to subjective or objective progression, and quality of life. Time off therapy in the intermittent arm was recorded. Results and limitations: We recruited 1045 patients, of which 918 responded to induction therapy and were randomised (462 to IHT and 456 to continuous MAB). OS was similar between groups ( p = 0.25), and noninferiority of IHT was demonstrated (hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.76-1.07). There was a trend for an interaction between PSA and treatment ( p = 0.05), favouring IHT over continuous therapy in patients with PSA 1 ng/ml (HR: 0.79; 95% CI, 0.61-1.02). Men treated with IHT reported better sexual function. Among the 462 patients on IHT, 50% and 28% of patients were off therapy for 2.5 yr or >5 yr, respectively, after randomisation. The main limitation is that the length of time for the trial to mature means that other therapies are now available. A second limitation is that T3 patients may now profit from watchful waiting instead of androgen-deprivation therapy. Conclusions: Noninferiority of IHT in terms of survival and its association with better sexual activity than continuous therapy suggest that IHT should be considered for use in routine clinical practice.

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Section: Discussionsupporting

confidence: 74%

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

Silva

Gonçalves

et al. 2014

European Urology

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“…Evaluation of OS was the primary endpoint in 4 studies [8-10,50,55,58] and TTP or time to androgen-independent was the primary endpoint in 7 studies [1,11,12,44-47,50-54,56,57] (Table 2). Five studies [1,8-10,44-47,55,58] were designed to evaluate the non-inferiority of IAD compared to CAD (Table 4).…”

Section: Resultsmentioning

confidence: 99%

Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis

Engel¹,

Clark²,

Reis³

et al. 2014

BMC Urol

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BackgroundProstate cancer is the most common cancer in older men in the United States (USA) and Western Europe. Androgen deprivation (AD) constitutes, in most cases, the first-line of treatment for these cases. The negative impact of CAD in quality of life, secondary to the adverse events of sustained hormone deprivation, plus the costs of this therapy, motivated the intermittent treatment approach. The objective of this study is to to perform a systematic review and meta-analysis of all randomized controlled trials that compared the efficacy and adverse events profile of intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic hormone-sensitive prostate cancer.MethodsSeveral databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), cancer-specific survival (CSS), time to progression (TTP) and adverse events. We performed a meta-analysis (MA) of the published data. The results were expressed as Hazard Ratio (HR) or Risk Ratio (RR), with their corresponding 95% Confidence Intervals (CI 95%).ResultsThe final analysis included 13 trials comprising 6,419 patients with hormone-sensitive prostate cancer. TTP was similar in patients who received intermittent androgen deprivation (IAD) or continuous androgen deprivation (CAD) (fixed effect: HR = 1.04; CI 95% = 0.96 to 1.14; p = 0.3). OS and CSS were also similar in patients treated with IAD or CAD (OS: fixed effect: HR = 1.02; CI 95% = 0.95 to 1.09; p = 0.56 and CSS: fixed effect: HR = 1.06; CI 95% = 0.96 to 1.18; p = 0.26).ConclusionOverall survival was similar between IAD and CAD in patients with locally advanced, recurrent or metastatic hormone-sensitive prostate cancer. Data on CSS are weak and the benefits of IAD on this outcome remain uncertain. Impact in QoL was similar for both groups, however, sexual activity scores were higher and the incidence of hot flushes was lower in patients treated with IAD.

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“…Several studies concluded that IADT had a better QoL outcome in hot flashes and sexual function, 9–11,19,20 although some studies found no clinically significant difference. 12,16 …”

Section: Resultsmentioning

confidence: 99%

“…Most published randomized controlled trial (RCTs) failed to show differences in survival between IADT and CADT, 9–14 yet a recent large trial of 1535 men reported that IADT is associated with worse survival outcomes than CADT in metastatic PCa. 15 Additionally, several studies found that IADT has an elevated disease-specific mortality compared with CADT, 9,10,15,16 whereas other studies have reported otherwise. 11,14 Therefore, we conducted this meta-analysis study combining currently available RCTs data to compare the efficacy of IADT relative to CADT with respect to all-cause and disease-specific mortality.…”

mentioning

confidence: 99%

Efficacy of Intermittent Androgen Deprivation Therapy vs Conventional Continuous Androgen Deprivation Therapy for Advanced Prostate Cancer: A Meta-analysis

Tsai

Penson

Makambi

et al. 2013

Urology

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OBJECTIVE To compare the efficacy of intermittent androgen deprivation therapy (IADT) vs continuous androgen deprivation therapy (CADT) for the treatment of advanced prostate cancer; we performed a meta-analysis of randomized controlled trials (RCTs), assessing the risks of disease progression, all-cause, and disease-specific mortality. MATERIALS AND METHODS We conducted a systematic search of several bibliographic systems to identify all RCTs of IADT in men with newly diagnosed metastatic or biochemical only prostate cancer. We abstracted outcome data, study characteristics, and participant demographics. We performed heterogeneity tests and calculated the summarized risk differences (RD) and risk ratios at 95% confidence intervals (CI), using inverse variance methods in random-effects approaches. RESULTS We identified 8 RCTs (N = 4664) comparing mortality between IADT and CADT. For all men combined, we observed small but nonsignificant differences in all-cause mortality (RD = 0.02, 95% CI = −0.02, 0.06), disease-specific mortality (RD = 0.04, 95% CI = −0.01, 0.08), and disease progression (RD = −0.03, 95% CI = −0.09, 0.04). Among the prespecified subgroup with histologically confirmed, newly diagnosed metastatic disease, we found no difference in overall survival (RD = 0.00, 95% CI = −0.09, 0.09). CONCLUSION We found no difference in overall survival, but a small increased risk in disease-specific survival for men treated with IADT relative to CADT was observed. IADT could be considered as an alternative to CADT because of better quality of life outcome. Patients should be informed of the possible risks and benefits of both therapies. More research confirming the benefits of IADT vs CADT is needed to inform treatment decisions.

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Continuous versus Six Months a Year Maximal Androgen Blockade in the Management of Prostate Cancer: A Randomised Study

Cited by 34 publications

References 19 publications

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

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

Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis

Efficacy of Intermittent Androgen Deprivation Therapy vs Conventional Continuous Androgen Deprivation Therapy for Advanced Prostate Cancer: A Meta-analysis

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