"The differences between the two groups were dramatic; bone mineral density increased among men taking bicalutamide while men in the leuprolide group lost bone," says Matthew Smith, MD, PhD, of the MGH Cancer Center, who led the study.
Since the male hormones called androgens can accelerate the development of prostate cancer, reducing their activity is a standard part of treating the disease. Most commonly this is done with drugs like leuprolide, called gonadotropin releasing hormone (GnRH) agonists, that stop the body's production of all sex hormones. However, totally blocking hormone activity can lead to potentially serious side effects such as loss of bone density, which increases the risk of fractures. Earlier studies by this MGH research team also showed that GnRH-agonist treatment often leads to unwanted weight gain and increased body fat.
Because bicalutamide blocks androgen activity in a way that does not reduce hormone levels in the blood, the research team wanted to see if using a single-drug treatment plan might avoid or reduce side effects. Earlier research had shown that bicalutamide alone is as effective as GnRH agonists for men with locally advanced prostate cancer.
The investigators enrolled 51 men with nonmetastatic prostate cancer who were randomly assigned to receive either bicalutamide or leuprolide treatment for one year. Although the participants knew which treatment they received, since the drugs are adminstered differently, those who gathered and analyzed the study's data did not know which patients were in which group.
At the end of the study period, blood levels of testosterone and the female hormone estradiol had risen significantly in the bicalutamide group but fallen in those receiving leuprolide. Bone mineral density, which decreased in the leuprolide group, had increased in participants receiving bicalutamide. While both groups had increases in body fat and decreased lean body mass, those changes were more pronounced in those receiving leuprolide. And unpleasant side effects – such as hot flashes, fatigue and sexual effects – were reported less frequently in men taking bicalutamide.
"Bicalutamide monotherapy may be an attractive alternative to standard hormone therapy for some men with non-metastatic prostate cancer," says Smith, who is an assistant professor of Medicine at Harvard Medical School. While bicalutamide is approved as monotherapy for prostate cancer in 55 countries, in the U.S. it is only approved in combination with GnRH-analog therapy.
The study's co-authors are Melissa Goode, Anthony Zietman, MD, Francis McGovern, MD, Hang Lee, PhD, and Joel Finkelstein, MD, all of the MGH. The study was supported by grants from the National Institutes of Health, the Doris Duke Charitable Foundation, and AstraZenaca, which markets bicalutamide under the brand name Casodex.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $400 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services. Additional information can be found at www.massgeneral.org.
Journal
Journal of Clinical Oncology