Recent data presented at the 2011 Genitourinary Cancers Symposium supports the growing consensus that intermittent androgen suppression (IADT) is no less effective than continuous androgen suppression at treating men with prostate cancer that recurs after radiotherapy. Lead investigator, Laurence Klotz, MD, chief of urology, Sunnybrook Health Sciences Center, and professor of surgery at the University of Toronto, said “Intermittent androgen suppression should be the standard of care for most patients with prostate-specific antigen
Dr. Klotz’s statement was the result of a phase III trial that enrolled 1386 men with non-metastatic prostate cancer who had a rising PSA 1 year after the completion of radiotherapy, suggesting that they have had a recurrence. The men were randomized to receive either androgen deprivation therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) continuously until they became castrate resistant (n = 696) or intermittently (n = 690) until progression, at which point they were switched to continuous ADT.
The medium overall survival (OS) reached 9.1 years for the continuous arm versus 8.8 years for the intermittent group (hazard ratio [HR], 1.02) This was not statistically significance for the study’s intermittent protocol (P = .009). At 7 years’ follow-up, disease-specific mortality was 18% in the intermittent group compared with 15% in the continuous arm, which according to Dr. Klotz said was not statistically significant (HR, 1.18; P = .24).
Castration resistance occurred at a median of 10 years’ follow-up for men who received continuous ADT compared with 9.8 years for men in the intermittent arm (HR, 0.80; P = .024). The fact that the median duration of OS was shorter than the median time to castration resistance in both groups points to the fact that several men died from causes other than prostate cancer.
What is also very interesting is that the rate of deaths unrelated to prostate cancer was 9% higher in the continuous arm than the intermittent group. Klotz theorized that the known metabolic effects of continuous ADT might account for some of the non-cancer deaths in this group.
In most phase II studies comparing intermittent ADT with continuous ADT, Klotz said men in the intermittent group were on treatment 50% of the time. On average, men randomized to intermittent ADT in Klotz’s study were actively treated 27% of the time, spending a median of 15.4 months on an LHRH and 37.6 months off.
At baseline, all the men had non-metastatic prostate cancer with a PSA level of >3 ng/ml. After randomization and initial flare blockade with an anti-androgen, the men in the intermittent group received an LHRH for 8 months. At that point, treatment stopped for men with normal PSA levels. After 8 months off therapy, those with a PSA level exceeding 10 ng/ml resumed therapy for another 8 months. Men whose PSA level rose above 10 ng/ml within 2 months of treatment discontinuation were switched to continuous therapy.
In each group, a similar proportion of patients experienced the most common adverse events, including erectile dysfunction, loss of libido, incontinence issues, fatigue, myocardial ischemia/infarction, and osteoporotic fracture. Patients in the intermittent ADT arm were significantly less likely to experience hot flashes than patients in the continuous arm, however (90% vs 93%; P = .04). Klotz said the investigators are still analyzing the data to assess quality-of-life issues, including off-treatment events.
Since there is an absence of studies to confirm that continuous ADT is associated with more non-cancer deaths than intermittent ADT, one can conclude that continuous or intermittent schedules confer a survival advantage over the other. The intermittent schedule does improve the quality of life, is easier to manage and also provides a cost savings.
For me personally, I have always been an intermittent guy and will continue to be an intermittent guy.
Joel T. Nowak, M.A., M.S.W.
Very helpful information that is supported by several other studies and various professionals. I am using this information today in a meeting with my oncologist who prefers me to continue a 2nd and 3rd year of non-interrupted ADT.