Intermittent androgen deprivation therapy limits side effects, improves quality of life

November 1, 2008

Intermittent androgen deprivation with a luteinizing hormone-releasing hormone analog causes fewer side effects and preserves quality of life compared with continuous combined androgen ablation, and many patients have prolonged treatment-free intervals.

Self-reported sexual activity improved in men treated with intermittent therapy, and the frequency of treatment-related adverse effects was significantly lower compared with continuous combined therapy, lead author Fernando E. Calais da Silva, MD, a urologist at the Hospital São José in Lisbon, Portugal said. Further, after 3.5 years of follow-up, 40% of patients had not returned for additional treatment.

"We have previously shown there is no difference in the risk of death between intermittent and continuous therapy," Dr. Calais da Silva said. "Now we show that intermittent therapy also is associated with fewer side effects and better quality of life."

Between October 1999 and September 2007, investigators in Portugal, Slovakia, Spain, the United Kingdom, and Greece enrolled 1,045 prostate cancer patients who had a median baseline PSA value of 15.9 ng/mL. More than 90% of the patients had T3 disease at entry; 13.5% had metastatic disease.

After induction therapy, the patients were randomized to intermittent treatment with an LHRH analog or to continuous therapy with the analog plus cyproterone acetate (not available in the U.S. for this indication). At randomization, the patients had a median PSA value of 1.0 ng/mL and a PSA range of 0.1 to 4.0 ng/mL. About half the patients had PSA values <1.0 ng/mL.

During a median follow-up of 2 years (maximum, 7 years), about three times as many men on continuous combined androgen deprivation had reported one or more side effect compared with men on intermittent therapy. The most common side effects (eg, hot flushes, gynecomastia, and headache) occurred significantly more often with continuous therapy (p<.0001).

About 30% of the men reported that they were sexually active before the trial, decreasing to 23% after induction therapy. Following randomization, patients receiving intermittent therapy had recovery of sexual function to 33% at 6 months, 29% at 12 months, and 28% at 24 months. In contrast, the proportion of men on continuous therapy who remained sexually active decreased to 20% at 6 months (p=.002), 19% at 12 months (p=.06), and 8% at 24 months (p=.0001).

Among patients on intermittent therapy, 20% returned for additional treatment within a year because of symptoms or rising PSA. Among patients followed for 3.5 years, 40% still have not returned for additional treatment.

A lower PSA value at randomization was associated with increased time off therapy: a median of 174 weeks among men whose PSA declined to <1.0 ng/mL compared with 100 weeks in men whose PSA ranged between 1.0 and 4.0 ng/mL (p=.05). Of the patients on intermittent therapy who resumed treatment, the median time on therapy was 16.7 weeks and was not predicted by PSA value at randomization.

"The early results from this study are consistent with those from previous studies of intermittent therapy," said Dr. Calais da Silva. "Patients treated with intermittent therapy have fewer side effects and better quality of life, especially with regard to sexual activity. Many of the patients on intermittent therapy have had long periods of time off therapy."