Formal discussant of the SWOG 9346 trial, William K. Oh, MD, Tisch Cancer Institute at the Mount Sinai School of Medicine, New York, said that at least 23 phase II trials have suggested that intermittent androgen deprivation therapy was safe and effective and that this practice has been broadly accepted.

“But accepting phase II studies is fraught with risk. Most trials had small numbers of patients, different stages of disease, and different rules for starting and stopping androgen deprivation therapy,” he noted. Several phase III trials have been completed that have suggested that intermittent androgen deprivation therapy was equally effective as continuous therapy, with fewer side effects, but all of these except one have been underpowered to look at a survival endpoint.  Only the NCIC PR7 trial in nonmetastatic disease with rising PSA post–radiation therapy demonstrated equivalent survival between continuous and intermittent androgen deprivation therapy.

Questions Raised

“The current study was a Herculean effort, taking more than 17 years since activation and including more than 3,000 patients. Cooperative groups undertake studies that no one else will conduct,” Dr. Oh commented.

In his view, the study raised several questions. Dr. Oh said definitions of extensive and minimal disease used in the trial “were confusing and nonstandard, and it is not clear whether this distinction is biologically relevant.”

“We need to be careful not to overinterpret the minimal and extensive disease results presented by Dr. Hussain. This was not a preplanned analysis,” Dr. Oh said. “I believe these [subgroup analysis] results are counterintuitive and should not be used to drive treatment decisions for patients,” he added.

Other Options

He said that continuous androgen deprivation remains the only standard of care for patients with newly diagnosed metastatic prostate cancer, and that patients who request intermittent therapy should be informed about the results of this trial. Some patients might opt for intermittent therapy based on preference for avoiding hormonal side effects.

“However, we should all remember that intermittent androgen deprivation remains an option for patients with nonmetastatic prostate cancer and rising PSA,” he stated.

New drugs such as abiraterone (Zytiga) and MDV3100 have produced excellent results in castrate-resistant prostate cancer and will be explored earlier in the course of disease, including hormone-sensitive metastatic prostate cancer. “If studies show that these drugs are successful in metastatic hormone-sensitive prostate cancer, that will prevent the need for lifelong androgen deprivation therapy,” Dr. Oh said. ■

Disclosure: Dr. Oh has served in a consulting or advisory role for Astellas Pharma, Janssen Biotech, and Medivation, and has received research funding from Millennium.