TY - JOUR
T1 - Locally advanced and metastatic prostate cancer treated with intermittent androgen monotherapy or maximal androgen blockade
T2 - results from a randomised phase 3 study by the South European uroncological group
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
C2 - 23582949
VL - 66
SP - 232
EP - 239
JO - European Urology
JF - European Urology
SN - 0302-2838
IS - 2
ER -