The authors of a study published April 4 in the New England Journal of Medicine concluded that intermittent hormone therapy is not as effective as continuous hormone therapy in treating many patients with metastatic prostate cancer, and are now counseling their patients to undergo the latter.
“Clinically, we found that intermittent was not as good as continuous, but we did not prove that the difference was statistically significant,” says Maha Hussain, MD, the study's principal investigator and associate director of clinical research at the University of Michigan Comprehensive Cancer Center in Ann Arbor. “There was a difference of about 7 months in median survival.”
Although the trial did not statistically prove absolutely that intermittent therapy was inferior, the authors believe from observing the study data that it is, she adds. Hormone therapy in hormone-sensitive prostate cancer has been shown to extend the lives of patients, but it can cause a variety of problematic side effects, including moodiness, hot flashes, sexual dysfunction, and bone loss. Historically, physicians prescribed intermittent or “pulsed” therapy in which treatment is stopped until signs of prostate cancer reappear in order to give patients relief from symptoms.
Dr. Hussain and colleagues undertook the study to prove that intermittent treatment was at least as good as or not significantly worse than continuous hormone therapy. The study, led by the Southwest Oncology Group (SWOG), followed 1535 men with metastatic prostate cancer for a median of almost 10 years. The study results indicated that men with less advanced prostate cancer who received intermittent therapy died an average of 2 years sooner than those on continuous therapy. The findings first received attention when they were announced last year at the annual meeting of the American Society of Clinical Oncology.
Survival for men with more metastatic disease was more modest, leading to the average of 7 months difference between the 2 therapies that Dr. Hussain discussed. Still, that survival difference is longer than other interventions, which only extend life for advanced metastatic patients by an average of 2 or 3 months, says Ian Thompson Jr., MD, director of the Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio and senior author of the study.
Dr. Hussain adds that although the study showed that intermittent therapy produced some gains in quality of life, the gains only occurred early on and that as they continued to follow patients, “those elements proved not significant.” As a result, she and colleagues recommended that continuous hormone treatment should be the standard of care. Still, she adds, “What we come up with in clinical trials is important for standards of care for the population at large, but it doesn't mean that an individual patient might not be served better with intermittent treatment. A doctor needs to explain to patients who are having significant side effects that they could explore intermittent, but that continuous therapy is the optimal choice from a survival perspective.”
The vast majority of patients with metastatic cancer in her practice have chosen continuous therapy, yet if they have significant side effects, Dr. Hussain said she and colleagues would consider palliating them with other measures or stopping the treatment for a period of time. “There has never been a trial testing intermittent therapy in patients with metastatic disease as big as this trial and looking at survival as the outcome,” she says. “We feel this is the definitive trial in the setting of metastatic disease. It may not have all the answers to all the questions, but I think the issue of intermittent therapy has been investigated quite a bit, and these are the best results we're going to get thus far.”