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

TY - JOUR

T1 - Locally advanced and metastatic prostate cancer treated with intermittent androgen monotherapy or maximal androgen blockade

T2 - European Urology

AU - Calais da Silva, Fernando

AU - Calais da Silva, Fernando Manuel

AU - Gonçalves, Frederico

AU - Santos, Américo

AU - Kliment, Jan

AU - Whelan, Peter

AU - Oliver, Tim

AU - Antoniou, Nicos

AU - Pastidis, Spiro

AU - Marques Queimadelos, Anton

AU - Robertson, Chris

PY - 2014/8

Y1 - 2014/8

N2 - 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 <4ng/ml after 3 mo of induction treatment were randomised to the IHT arm (stoppedtreatment and restarted on CPA 300 mg/d monotherapy if PSA rose to ≥20 ng/ml orthey were symptomatic) or the continuous arm (CPA 200 mg/d plus monthly LHRHanalogue).Outcome measurements and statistical analysis: Primary outcome measurement was OS. Secondary outcomesincluded 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: Werecruited 1045 patients, of which 918 responded to induction therapy and wererandomised (462 to IHT and 456 to continuous MAB). OS was similar betweengroups (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 aninteraction between PSA and treatment (p=0.05), favouring IHT over continuoustherapy in patients with PSA ≤1 ng/ml (HR: 0.79; 95% CI, 0.61-1.02). Men treatedwith 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 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.

AB - 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 <4ng/ml after 3 mo of induction treatment were randomised to the IHT arm (stoppedtreatment and restarted on CPA 300 mg/d monotherapy if PSA rose to ≥20 ng/ml orthey were symptomatic) or the continuous arm (CPA 200 mg/d plus monthly LHRHanalogue).Outcome measurements and statistical analysis: Primary outcome measurement was OS. Secondary outcomesincluded 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: Werecruited 1045 patients, of which 918 responded to induction therapy and wererandomised (462 to IHT and 456 to continuous MAB). OS was similar betweengroups (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 aninteraction between PSA and treatment (p=0.05), favouring IHT over continuoustherapy in patients with PSA ≤1 ng/ml (HR: 0.79; 95% CI, 0.61-1.02). Men treatedwith 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 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.

KW - maximal androgen blockade

KW - intermittent antiandrogen therapy

KW - prostate cancer

KW - cyproterone acetate

KW - prostate specific antigen

KW - triptorelin

UR - http://www.sciencedirect.com/science/journal/03022838

U2 - 10.1016/j.eururo.2013.03.055

DO - 10.1016/j.eururo.2013.03.055

M3 - Article

VL - 66

SP - 232

EP - 239

JO - European Urology

JF - European Urology

SN - 0302-2838

IS - 2

ER -