A long-term, multicenter Phase III international clinical trial comparing two common therapies for men with hormone-sensitive metastatic prostate cancer has found that intermittent hormonal therapy is less effective than continuous hormonal therapy in men with minimal disease spread.

There was a two-year difference in median survival among these men, favoring men who received continuous therapy.

Among men with more extensive disease spread, however, the results indicate that intermittent and continuous therapy are comparably effective.

"Some doctors recommend intermittent hormonal therapy to men with metastatic prostate cancer, believing it will reduce their risk of side effects without compromising their outcome, but these findings demonstrate a clear downside to this approach for certain men," said Maha Hussain, MD, Professor of Medicine and Urology at the University of Michigan Comprehensive Cancer Center and the study's lead author.

"The findings clearly demonstrate that intermittent hormonal therapy is not safe for all patients with metastatic prostate cancer. They will be practice changing for many doctors in the U.S. and abroad who routinely use intermittent therapy."

Prostate cancer is fueled by the male hormone testosterone; hormonal therapy is used to turn off testosterone production and thereby stop cancer growth.

But hormonal therapy has side effects that impair quality of life, including reduced sexual drive and potency, hot flashes and weight gain. Based on early scientific and clinical data, doctors have thought for some time that intermittent hormonal therapy (stopping and restarting treatment periodically) could decrease these side effects and perhaps delay the resistance to hormonal therapy that most metastatic prostate cancers develop.

Intermittent hormonal therapy appeared to be safe in prior studies, but those studies generally included either men whose only evidence of prostate cancer progression was an increase in PSA level (as opposed to X-ray evidence of disease spread, for example), or men with wide-ranging stages of disease (not just metastatic cancer).

This National Cancer Institute-sponsored intergroup study (led by SWOG) was designed to see if intermittent hormonal therapy achieved survival comparable with continuous therapy among men with metastatic prostate cancer. The trial included more than 1,500 men with hormone-sensitive metastatic prostate cancer whose PSA fell to 4 ng/ml or less after 7 months of continuous hormonal therapy.

The men were then randomly assigned to receive intermittent hormonal therapy (770 patients) or continuous hormonal therapy (759 patients). Because treatment was given periodically, patients in the intermittent therapy group received, on average, about half as much hormonal therapy as those in the continuous therapy group.

After a median follow-up of 9.2 years, median overall survival in men with minimal disease spread (no spread beyond the spine, pelvis, and lymph nodes) was 7.1 years for those who received continuous therapy versus 5.2 years for those who received intermittent therapy. Among men with more extensive disease spread, median overall survival was similar in both arms (4.4 years for the continuous therapy group vs. 5 years for the intermittent group).

Source: ASCO