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Intermittent androgen suppression appears to be safe and feasible in stage IV prostate cancer patients, according to a multicenter, randomized study presented by Dr. Kurt Miller.
About 66% of the intent-to-treat population progressed whether they received intermittent or continuous treatment. Time to progression was longer in the intermittent blockade arm of the trial, 16.6 months vs. 11.5 months, but this difference was not significant.
The median time to death from any cause was 51 months in the intermittent arm and 54 months in the continuous arm. No significant differences were reported in the incidence of adverse events, serious adverse events, or any other safety parameter.
The study adds to growing evidence that intermittent therapy—while it cannot yet be considered the standard of therapy—is not inferior to continuous androgen suppression and may improve quality of life, said Dr. Miller, chairman of urology at Benjamin Franklin Medical Center, Berlin.
Conducted in Germany, the trial compared schedules for treatment with goserelin plus bicalutamide in patients with histologically confirmed D1 or D2 adenocarcinoma of the prostate. All told, 478 patients had a run-in phase of continuous androgen blockade for 24 weeks. A total of 335 patients whose prostate specific antigen (PSA) dropped to less than 4 ng/mL or fell more than 90% were randomized to intermittent or continuous therapy. Patients with PSA progression were removed from the study and given second-line treatment.
In the intermittent arm, treatment resumed if PSA exceeded 10 ng/mL, and stopped if it fell to less than 4 ng/mL. Progression was defined as a threefold rise in PSA or clinical progression based on bone scans or soft tissue metastasis. "This was not an equivalency study; it was a study with a hypothesis at that time that intermittent blockade is superior to continuous blockade," Dr. Miller explained.
The first patient entered the study in 1997, and the last left in 2006. About 40% of patients were stage D2, and the median age was 70 years. Baseline PSA was reported as 158 ng/mL in the intermittent blockade group and 139 ng/mL in the continuous blockade arm.
The researchers found no differences in pain, impairment of social functioning, emotional well being, and vitality. Trends in general well-being and sexual functioning favored intermittent blockade.
"As in previous studies, there was a bit more urinary retention in the intermittent arm—5% versus 1%—and There was no difference in cardiac events, which has been reported by other investigators in the same setting," Dr. Miller added.
Continuous androgen blockade is a waste of money, according to discussant Dr. Ian Tannock of Princess Margaret Hospital in Toronto. "I think what is happening is that companies make a huge profit out of combined androgen blockade and, despite results of a meta-analysis, they push people to look at individual trials or subgroup analyses to try to suggest that this is something to be considered and is even widely used," he said in an interview.
In its 2007 clinical practice guidelines, ASCO recommends that "combined androgen blockade be considered as part of the overall treatment regimen for prostate cancer," and that "the [expert] panel suggests that current data [are] insufficient to support the use of intermittent ADT outside of clinical trials."
Dr. Tannock said. "There is now sufficient evidence that intermittent androgen blockade should be regarded as a reasonable and alternative strategy for managing hormone-sensitive prostate cancer, and it's what I would choose for myself."
Miller K. et al. Randomised prospective study of intermittent versus continuous androgen suppression in advanced prostate cancer. Abstract 5015.
Commentary |
In my urologic oncology practice, devoted mostly to men with prostate cancer, I routinely discuss intermittent hormonal therapy (IHT) with patients. The presentation by Dr. Kurt Miller and colleagues is very important in this regard. In the era of longer survivals, less blanket acceptance of side effects, decreasing reimbursements for luteinizing hormone-releasing hormone (LH-RH) agonists, and recognition of the dangers of long-term hormonal therapy, I recommend IHT more commonly, as do my colleagues, weighing alternatives with most men—those with de novo metastatic disease/biochemical recurrence and those with undetectable PSA who have been on hormones for several years. With the new data from Miller et al., I will feel even more confident that IHT is comparable to continuous therapy. In this setting when using IHT, I tend to favor complete hormonal therapy (an LH-RH agonist with an oral antiandrogen) while men are in the "on" phase. — Judd W. Moul, M.D.
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