Per-Anders Abrahamsson1. 1. Department of Urology, Lund University, Malmö University Hospital, S-224 01, Malmö, Sweden. per-anders.abrahamsson@skane.se
Abstract
CONTEXT: The well-known side-effect profile of androgen-deprivation therapy (ADT) has significant quality-of-life (QoL) implications. Intermittent androgen deprivation (IAD) alternates androgen blockade with treatment cessation to allow hormonal recovery between treatment cycles, thus potentially improving tolerability and QoL. OBJECTIVE: To evaluate available evidence regarding the efficacy and tolerability of IAD and assess its value in the treatment of prostate cancer (PCa). EVIDENCE ACQUISITION: Key phase 2/3 clinical trials of IAD in PCa published within the last 10 yr were identified on Medline using the terms prostatic neoplasms [MeSH], intermittent androgen suppression, intermittent hormonal deprivation, intermittent androgen deprivation, and intermittent hormonal therapy. Abstracts from trials reported at 2008-2009 conferences were also included. EVIDENCE SYNTHESIS: Data from 19 phase 2 studies are discussed with respect to prostate-specific antigen values for treatment suspension/reinitiation, treatment regimens, cycle lengths, testosterone normalisation, and tolerability. Outcome data were promising: Most trials reported an improvement in QoL during the off-therapy periods. Interim data from eight phase 3 trials comparing IAD and continuous androgen deprivation (CAD) support the phase 2 results. IAD generally showed comparable efficacy to CAD with respect to various outcomes, including biochemical progression, progression-free survival, and overall survival. However, IAD was significantly better than CAD with respect to 3-yr risk of progression in one study, and it demonstrated tolerability benefits, particularly with respect to sexual function. Patients most likely to benefit from IAD and factors predictive of poor response are also discussed. CONCLUSIONS: IAD seems to be as effective as CAD while showing tolerability and QoL advantages, especially recovery of sexual potency; however, there are as yet insufficient data to determine whether IAD has the potential to prevent or reverse the long-term complications associated with ADT.
CONTEXT: The well-known side-effect profile of androgen-deprivation therapy (ADT) has significant quality-of-life (QoL) implications. Intermittent androgen deprivation (IAD) alternates androgen blockade with treatment cessation to allow hormonal recovery between treatment cycles, thus potentially improving tolerability and QoL. OBJECTIVE: To evaluate available evidence regarding the efficacy and tolerability of IAD and assess its value in the treatment of prostate cancer (PCa). EVIDENCE ACQUISITION: Key phase 2/3 clinical trials of IAD in PCa published within the last 10 yr were identified on Medline using the terms prostatic neoplasms [MeSH], intermittent androgen suppression, intermittent hormonal deprivation, intermittent androgen deprivation, and intermittent hormonal therapy. Abstracts from trials reported at 2008-2009 conferences were also included. EVIDENCE SYNTHESIS: Data from 19 phase 2 studies are discussed with respect to prostate-specific antigen values for treatment suspension/reinitiation, treatment regimens, cycle lengths, testosterone normalisation, and tolerability. Outcome data were promising: Most trials reported an improvement in QoL during the off-therapy periods. Interim data from eight phase 3 trials comparing IAD and continuous androgen deprivation (CAD) support the phase 2 results. IAD generally showed comparable efficacy to CAD with respect to various outcomes, including biochemical progression, progression-free survival, and overall survival. However, IAD was significantly better than CAD with respect to 3-yr risk of progression in one study, and it demonstrated tolerability benefits, particularly with respect to sexual function. Patients most likely to benefit from IAD and factors predictive of poor response are also discussed. CONCLUSIONS:IAD seems to be as effective as CAD while showing tolerability and QoL advantages, especially recovery of sexual potency; however, there are as yet insufficient data to determine whether IAD has the potential to prevent or reverse the long-term complications associated with ADT.
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