Quality of life better after intermittent vs. continuous androgen deprivation therapy

Chicago-Intermittent androgen ablation for advanced prostate cancer results in progression-free survival that is comparable to that of continuous therapy, but with better quality of life, according to data from a multicenter German study.

After a median follow-up of 50.5 months, 65.45% of patients receiving intermittent therapy had progressed, compared with 66.47% of those who received continuous therapy. Time to progression and overall survival also did not differ between treatment groups, Kurt Miller, MD, reported at the 2007 American Society of Clinical Oncology annual meeting here.

"We are still far enough away [from a definite answer] that we cannot consider intermittent androgen as the standard of therapy," advised Dr. Miller, chairman of urology at Benjamin Franklin Medical Center in Berlin. "In selected patients, however, it is very unlikely that we will make a mistake if we offer this type of treatment."

In an effort to clarify the clinical situation, Dr. Miller and colleagues prospectively compared intermittent versus continuous androgen ablation in patients with advanced prostate cancer. All patients received 6 months of combined hormonal therapy. Those whose PSA values decreased to <4.0 ng/mL or by more than 90% were randomized to continue hormonal treatment or to stop therapy and resume it only when serum PSA increased to >10.0 ng/mL. Intermittent therapy continued on the basis of the predefined changes in PSA values.

Subsequently, 335 patients were randomized to continuous or intermittent androgen deprivation therapy. The primary endpoint was time to clinical or biochemical progression. Secondary endpoints were overall survival, quality of life, and tolerability. Patients had a mean age of about 70 years. D2 disease accounted for 41% of patients on intermittent therapy and 35% of those on continuous therapy. Baseline PSA was 158.0 ng/mL in the intermittent-therapy cohort and 139.0 ng/mL in patients randomized to continuous therapy.

Follow-up finds trends

At the last follow-up, 108 of 165 patients on intermittent therapy had progressed, as had 113 of 170 on continuous therapy. Median time to progression was 16.6 months with intermittent hormonal treatment and 11.5 months with continuous therapy. A separate analysis of patients with D2 disease showed no difference in the time to progression. Intermittent therapy was associated with a trend toward a longer progression-free interval in patients with D1 disease (p=.07).

Additional analyses showed no significant differences between the types of treatment in time to progression for patients who had detectable or undetectable PSA values at baseline.

Quality of life assessments showed no overall difference in pain, impairment in social function, emotional well being, vitality, restricted activity, or physical capabilities. A trend favoring intermittent therapy emerged from data on general well being and sexual functioning.

Adverse events were reported by about half the patients in each treatment group, and serious adverse events occurred in about one-third of patients in each group. Between 7% and 8% of patients in each group discontinued treatment because of adverse events.

Dr. Miller reported that 88% of patients on intermittent hormonal therapy were off therapy more than 50% of the time. Time to normalization of testosterone levels after discontinuation of treatment was 70 days.

Findings from the study are consistent with other recent presentations, Dr. Miller noted. At the 2006 ASCO meeting, Spanish investigators (daSilva et al, abstract 4513) reported no difference in progression-free survival among 626 patients randomized to intermittent or continuous androgen ablation. Patients on intermittent therapy had better quality of life, and continuous therapy was associated with an increased risk of cardiovascular events. At this year's AUA annual meeting, investigators from Germany and Italy (Tunn et al, abstract 600) reported no difference in progression-free survival in 167 patients randomized to continuous or intermittent hormonal treatment, but intermittent therapy was associated with a lower rate of hot flashes.