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Publications

Intermittent versus continuous androgen deprivation in prostate cancer.

By:
Contributors: Bryan Donnelly, MD, MSc, FRCSC, Peter Venner, MD, FRCPC
Urol Oncol. 2014 Aug;32(6):936-7. doi: 10.1016/j.urolonc.2014.01.009.

Abstract

BACKGROUND:

Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgendeprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence.

METHODS:

Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization.

RESULTS:

A total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events.

CONCLUSIONS:

Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.).

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Our First Participant!

Thanks to the participation from men with suspected prostate cancer and men diagnosed with prostate cancer, we will be able to measure if our “tests” can reveal the true nature of prostate cancer and if the tests or biomarkers can diagnose prostate cancer and tell us what cancers are more aggressive.

As part of the Alberta Prostate Registry and Biorepository, patients will be entered into our study, in which blood and other samples are collected over time and their health outcomes are recorded over many years. Patients will follow standard medical advice and care through their doctors. Our team collect biospecimens and information related to general health and cancer behavior over time.

Rather than being frightened by the word ‘cancer’, we want to learn how to predict serious and morbid prostate cancer complications well before they happen, so that we can weigh carefully the pros and cons of available treatments.

In the process, we expect to identify new and important advantage points for better therapies to be developed. The word “cancer” may be scary, but what is truly scary is unawareness.

“It makes me very happy to be able to contribute to find better ways to diagnose prostate cancer.”

- Mr. Garcia