Maha Hussain, MD
An international, multicenter, phase III clinical trial launched in 1995 has demonstrated that patients with metastatic, hormone-sensitive prostate cancer and minimal disease spread experience a two-year boost in median survival when treated with continuous, rather than intermittent, hormonal therapy. The results were announced June 2 during the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO).
While androgen-deprivation drugs that restrict the production of testosterone are the standard therapy for patients with metastatic prostate cancer, they cause side effects, including reduced sexual drive and potency, hot flashes, and weight gain. In addition, most men treated with hormonal therapies become resistant to the treatments, said Maha Hussain, MD, professor of medicine and urology at the University of Michigan Comprehensive Cancer Center, and the study’s lead author.
“Earlier experimental laboratory evidence indicated that intermittent hormonal treatment could prolong the duration of disease response, and data from clinical trials from the 1990s suggested the feasibility of intermittent treatment and the potential for improvements in side effects,” Hussain said, “but these findings demonstrate a clear downside to this approach for certain men. They will be practice-changing for many doctors in the US and abroad who routinely use intermittent therapy.”
Despite the marked difference in the results of the two treatment modalities for men with minimal disease spread, the National Cancer Institute-sponsored study did not demonstrate any meaningful difference in intermittent versus continuous therapy in men with more extensive disease spread.
“These observations suggest potential inherent biological differences,” Hussain said, “and warrant further evaluation.”
The study included 1,535 men who were newly diagnosed with metastatic prostate cancer, had prostate-specific antigen (PSA) levels ≥5 ng/mL, and may have been treated previously with neoadjuvant androgen-deprivation therapy or finasteride. After seven months of continuous treatment with hormonal therapies goserelin and bicalutamide, the men were eligible to participate in the study because their PSA levels had dropped to ≤4 ng/mL. They were randomly assigned to either continuous or intermittent therapy with the same two drugs. Those in the intermittent arm received about half as much hormonal therapy as those in the group treated continuously.
The primary endpoint was overall survival, and a co-primary endpoint was quality of life.
For all patients in the study, median survival was 5.8 years on continuous therapy and 5.1 years on intermittent therapy.
When the investigators conducted a secondary analysis of subgroups of patients with metastatic prostate cancer, they found that men with minimal disease spread had a median survival of 7.1 years with continuous treatment and 5.2 years with intermittent treatment. Meanwhile, patients with extensive disease spread experienced a median survival of 4.4 years with continuous therapy and 5.0 years with intermittent therapy—this difference was not statistically significant.
“We found it striking and surprising,” Hussain said of the results for men with minimal disease spread, “because it goes against conventional belief based on all trials done thus far with this disease.”
A separate abstract by Carol Moinpour, et al, also released during the ASCO meeting, highlights the study’s quality-of-life results. Three months after baseline, the authors wrote, patients on the continuous therapy arm reported “statistically significantly more impotence and less libido” than those on the intermittent arm. Those in the intermittent group also enjoyed “slightly better” emotional function, the research team wrote.
Hussain M, Tangen CM, Higano CS, et al. Intermittent (IAD) versus continuous androgen deprivation (CAD) in hormone sensitive metastatic prostate cancer (HSM1PC) patients (pts): Results of S9346 (INT-0162), an international phase III trial. J Clin Oncol. 2012;30 (suppl; abstr 4).
Moinpour C, Berry DL, Ely B, et al. Preliminary quality-of-life outcomes for SWOG-9346: Intermittent androgen deprivation in patients with hormone-sensitive metastatic prostate cancer (HSM1PC)—Phase III. J Clin Oncol. 2012;30 (suppl; abstr 4571).
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