Abstract
Intermittent androgen deprivation is increasingly used as an alternative to continuous life-long androgen deprivation therapy for men with advanced or recurrent prostate cancer. Two recent phase iii trials have clarified the benefits of intermittent therapy. The Canadian-led pr.7 trial in men with nonmetastatic disease and prostate-specific antigen recurrence after definitive local therapy showed that intermittent therapy resulted in survival equivalent to that with continuous therapy, with significant improvements in quality of life. Patients on intermittent therapy experienced improved bone health, fewer metabolic and hematologic disturbances, fewer hot flashes, and improved sexual function. In men with metastatic disease, the data are less clear. The long-awaited results of the Southwest Oncology Group 9346 trial, comparing intermittent with continuous therapy in metastatic disease, showed no difference in overall survival. Post hoc stratification analysis showed a worse outcome in patients with "minimal" metastatic disease, and no difference in those with widespread bone metastases. The significance of that observation is in dispute. The present review also addresses practical issues in the use of intermittent therapy, including patient selection, follow-up, and therapy cycling. The recent results of randomized clinical trials now establish that intermittent androgen deprivation therapy is an approach that should be considered the standard of care in most patients with nonmetastatic prostate cancer requiring hormonal therapy and in selected patients with metastatic disease. Level i evidence supports the oncologic equivalence of intermittent compared with continuous androgen blockade in men with biochemical failure.Compared with continuous androgen deprivation, intermittent therapy demonstrates improved quality of life and fewer side effects.Patient selection for intermittent therapy is important to maintain good oncologic results.Monitoring of prostate-specific androgen response and duration of off-treatment intervals allow for stratification of patients by risk of progression.
Highlights
Androgen deprivation therapy for prostate cancer was first described in 1941 by Huggins and Hodges
The present review addresses practical issues in the use of intermittent therapy, including patient selection, follow-up, and therapy cycling
In 1986, my colleagues and I first described intermittent androgen deprivation for advanced prostate cancer in a report of 20 patients with metastatic disease treated with diethylstilbestrol, in whom the therapy was discontinued once they demonstrated a good clinical response
Summary
Two recent phase iii trials have clarified the benefits of intermittent therapy. The Canadian-led pr.[7] trial in men with nonmetastatic disease and prostate-specific antigen recurrence after definitive local therapy showed that intermittent therapy resulted in survival equivalent to that with continuous therapy, with significant improvements in quality of life. Patients on intermittent therapy experienced improved bone health, fewer metabolic and hematologic disturbances, fewer hot flashes, and improved sexual function. The long-awaited results of the Southwest Oncology Group 9346 trial, comparing intermittent with continuous therapy in metastatic disease, showed no difference in overall survival. Post hoc stratification analysis showed a worse outcome in patients with “minimal” metastatic disease, and no difference in those with widespread bone metastases. The present review addresses practical issues in the use of intermittent therapy, including patient selection, follow-up, and therapy cycling
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