Men diagnosed with early-stage prostate cancer who received daily doses of tadalafil to prevent radiotherapy (RT) treatment-related erectile dysfunction (ED) gained no significant sexual function benefit compared with those who received a placebo, according to results of a clinical trial published in the April 2, 2014 issue of JAMA.
Conducted by the Radiation Therapy Oncology Group (RTOG) Community Clinical Oncology Program (CCOP), the RTOG 0831 study is the first to evaluate tadalafil for ED prevention in men treated with RT for prostate cancer. "For many men faced with decisions about prostate cancer treatment options, maintaining sexual function is the number one side effect concern," says the trial's principal investigator (PI) Deborah Bruner, Ph.D., R.N., F.A.A.N., professor of nursing and associate director for outcomes research at the Winship Cancer Institute of Emory University in Atlanta. Data were analyzed for 221 study participants who reported having intact erectile function prior to RT treatment and were equally randomized to receive daily doses of either tadalafil or a placebo. During RT treatment, the study participants completed standardized assessments of erectile function at weeks 2 and 4 and between weeks 20 and 24. Post-treatment assessments were completed between weeks 28 and 30 and at one year after the start of treatment. The trial was carried out at 76 facilities throughout the United States and Canada.
ED resulting from radiotherapy is thought to occur due to vascular damage and impaired blood flow to the penis. "Since PDE5 inhibitors promote blood flow to the penis, we hypothesized that improving blood flow during radiotherapy treatment with daily administration of tadalafil would help to prevent blood vessel damage and related erectile dysfunction," says Bruner. "Tadalafil was selected for the study drug because of its longer duration of action than other phosphodiesterase-5 (PDE-5) inhibitors which allowed for a continuous blood level of the drug with daily dosing."
"In the area of prostate cancer surgery, urologists very frequently use PDE-5 inhibitor medications to restore erectile function and it was unknown whether using these medications in the context of radiotherapy treatment might provide a preventative benefit to patients," says lead author Thomas M. Pisansky, MD, a co-investigator of the study and a professor of radiation oncology at the Mayo Clinic in Rochester, MN. "This study sought to identify any benefit with the administration of tadalafil for preventing erectile dysfunction and we found no discernable benefit."
"While several small, single institution studies suggest that PDE-5 agents may have a role in preventing ED in men undergoing RT, we now know that it is unnecessary—or over treating—to prescribe tadalafil as preventative agent," says Bruner. "Prescribing the drug for this purpose could result in unnecessary medical expenses for patients and, even though the side effects are mild, there are still some side effects."
The authors report that the study has "several strengths supporting generalization of its results to men yet to receive radiotherapy for prostate cancer." The wide range of clinical sites carrying out the study were all required to adhere to exacting RT specifications that involved keeping the radiation dose away from the erectile tissues. "Upon review of the radiation dose delivered to patients in the study, I observed that specifications were consistently followed across all sites," says Pisansky. Additionally, the study participants were a racially diverse group recruited across a wide geographic distribution. "African American men bare a higher burden of prostate cancer and the percentage of African American men enrolled in the trial was higher than the national percentage which is very important in a disease in which they bare the highest burden," says Bruner.
The authors suggest the need for more research to identify ED prevention strategies after prostate cancer therapy that may include alternative PDE-5 inhibitor agents or dosing schedules or further refinements of radiotherapy delivery. "This rigorously designed trial provides evidence about the use of tadalafil for the prevention of erective dysfunction in men undergoing radiotherapy," says Walter J. Curran, Jr., M.D., NRG Oncology Group Co-Chairman and Executive Director of the Winship Cancer Institute of Emory University in Atlanta. "Having 76 institutions elect to carry out the research—the majority in community-based settings—speaks to both the high interest of clinicians across the county to identify preventative strategies for erectile dysfunction for their patients and the strong generalizability of the study results."
As of March 1, 2014, RTOG joined with the National Surgical Adjuvant Breast and Bowel Project and the Gynecologic Oncology Group to conduct multi-center clinical trials as NRG Oncology within the National Cancer Institute National Clinical Trials Network.
The study was funded by the National Cancer Institute Fund (ClinicalTrials.gov number, NCT00931528) through grants U10 CA37422 and U10 CA21661. Eli Lilly and Company provided the tadalafil medication and placebo for the study.