Androgen deprivation therapy administered to men with prostate cancer did not increase the risk of cardiovascular death, according to meta-analysis of prospective randomized trials. In addition, the study published in the Dec. 7 issue of the Journal of the American Medical Association found that the therapy was associated with a lower risk of prostate cancer-specific mortality and all-cause mortality.
Paul L. Nguyen, MD, a radiation oncologist at the Dana-Farber Cancer Institute at Brigham and Women’s Hospital in Boston, and colleagues conducted the study in response to conflicting reports about cardiovascular risks associated with androgen deprivation therapy (ADT), a treatment for men with advanced prostate cancer and sometimes for men with early stage cancer. Based on some previous findings of adverse effects, the American Heart Association and other societies published a cautionary report on the drug, and the FDA issued a safety warning.
For their analysis, the authors pored through MEDLINE and EMBASE citations from Jan. 1, 1966, to April 11, 2011, and the Cochrane Central Register of Controlled Trials database through April 11, 2011 to identify studies for inclusion. From an initial group of 1,041 articles, they identified eight Phase 3 randomized controlled clinical trials of ADT that included 4,141 non-metastatic prostate cancer patients with one-year follow-up and mortality outcomes.
They used the Cochrane Q statistic to assess heterogeneity among the trials and other statistical methods to ensure that variation across the studies was due to heterogeneity and not chance. They also performed subanalyses to gauge relative risk among subgroups based on duration of treatment. Median follow-up was 7.6 to 13.2 years.
They found similar rates of cardiovascular death between the ADT group and the placebo group, 11 percent and 11.2 percent, respectively; and similar rates of cardiovascular death in trials of up to three years (11.5 percent for both) and less than six months (10. 5 and 10.3 percent). ADT use was associated with lower rates of prostate cancer-specific mortality (13.5 percent vs. 22.1 percent for the placebo group) and all-cause mortality (37.7 percent vs. 44.4 percent).
“Overall, the results of our study should be generally reassuring to most men with unfavorable-risk prostate cancer considering ADT, because it was associated with improved survival without a measurable excess in cardiovascular mortality, but a few important points need to be raised,” they wrote.
Those caveats include the fact that the trials were not stratified by preexisting cardiovascular comorbidities, which might show subgroups of men with cardiovascular disease were at risk with ADT. They recommended conducting a controlled randomized trial of patients with high-risk cardiac histories. They noted the possibility of underreporting or misclassifying cardiac deaths in the trials as well.