Intermittent Androgen Suppression Offers Small Gains for Prostate Cancer Patients



LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

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