Duration of androgen suppression in the treatment of prostate cancer.

BACKGROUND: The combination of radiotherapy plus long-term medical suppression of androgens (> or = 2 years) improves overall survival in patients with locally advanced prostate cancer. We compared the use of radiotherapy plus short-term androgen suppression with the use of radiotherapy plus long-term androgen suppression in the treatment of locally advanced prostate cancer. METHODS: We randomly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of androgen suppression to two groups, one to receive no further treatment (short-term suppression) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist (long-term suppression). An outcome of noninferiority of short-term androgen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival, with a one-sided alpha level of 0.05. An interim analysis showed futility, and the results are presented with an adjusted one-sided alpha level of 0.0429. RESULTS: A total of 1113 men were registered, of whom 970 were randomly assigned, 483 to short-term suppression and 487 to long-term suppression. After a median follow-up of 6.4 years, 132 patients in the short-term group and 98 in the long-term group had died; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group. The 5-year overall mortality for short-term and long-term suppression was 19.0% and 15.2%, respectively; the observed hazard ratio was 1.42 (upper 95.71% confidence limit, 1.79; P=0.65 for noninferiority). Adverse events in both groups included fatigue, diminished sexual function, and hot flushes. CONCLUSIONS: The combination of radiotherapy plus 6 months of androgen suppression provides inferior survival as compared with radiotherapy plus 3 years of androgen suppression in the treatment of locally advanced prostate cancer. (ClinicalTrials.gov number, NCT00003026.)

Intermittent maximal androgen blockade in patients with metastatic prostate cancer: an EORTC feasibility study.

OBJECTIVES: In preparation of an intercontinental Phase III trial comparing continuous maximal androgen blockade (MAB) to intermittent androgen suppression (IAS) in untreated metastatic prostate cancer, a feasibility study on IAS was accomplished. METHODS: 107 patients (median follow-up 92 weeks) were treated with MAB until a PSA nadir was reached. Nadir was defined as PSA below 20 ng/ml corresponding to PSA reduction by at least 80% of baseline value. Criteria for restarting treatment was PSA >20 ng/ml and PSA > nadir + 50%. Trials aim was to assess the likelihood that 80% of patients would reach a first nadir and that 80% of these would also reach a second nadir. RESULTS: 51.4% of patients had some degree of pain at entry, 27.1% had >15 hot spots, 23.7% demonstrated obstruction. Only 17.8% had normal potency, 56.1% were totally impotent. One to seven cycles of treatment were given. 76.6% of patients reached a 1st nadir after a median of 19 weeks of treatment, 84.1% of these started the 2nd cycle and 71% of them reached a 2nd nadir after a median of 13.6 weeks. Median time off-treatment was 14.3 and 16.0 weeks corresponding to 38.4% and 48.5% of the duration of each cycle. A similar proportion of patients was reported to be potent during follow-up compared to baseline. 32.7% of patients died during follow-up, 82.9% of prostate cancer. CONCLUSION: Around 75% of the patients achieved a nadir at each cycle. The concept of IAS seems to be feasible and warrants further investigation.