One of the unsettled debates in our advanced prostate cancer world surrounds the issue of continuous vs. intermittent hormone therapy (IHT). Traditionally, hormone therapy was continuous, or once you started you never stopped the treatment. As many of us know, hormone therapy is notorious for damaging the quality of life. Hot flashes, loss of libido, neuropathy etc. are just a few of the many side effects many of us experience.

With the goal of minimizing these negative side effects, some of us, with increasing numbers, have elected to periodically stop the therapy until such time that our PSA increases to some undetermined number. Once our number hits the goal (which is different for each of us and dependent upon the PSA velocity) we elect to go back “on” the blockade. Many of us do experience a return of our testosterone during these “off” periods and thus feel much better. Our libido increases, the neuropathy abates and live often normalizes.

In my case, when I elected to go intermittent, my oncologist told me that it is considered experimental and he could not recommend the intermittent schedule. I still elected to go intermittent anticipating that I would get about 9 months time before I would have to go back and restart the therapy. To my great surprise and pleasure I have been on an “off” period for over three (3) years. My PSA has begun to climb, but I am hoping to stay “off” for another year!

There have been few randomized studies comparing intermittent hormonal therapy (IHT) with continuous therapy for the treatment of advanced prostate cancer (PCa). So, the Department of Urology, Centro Hospitalar de Lisboa Central, Lisbon, Portugal conducted a study to determine whether intermittent therapy is associated with a shorter time to progression.

Seven hundred and sixty six (766) patients with locally advanced or metastatic PCa received a 3-mo induction treatment. The six hundred twenty six (626) patients whose prostate-specific antigen (PSA) level decreased to < 4ng/ml or to 80% below the initial value were randomized for this trial.Patients received cyproterone acetate (CPA) 200mg for 2 wk (from the NCI dictionary – The acetate salt of a synthetic steroidal antiandrogen with weak progestational and antineoplastic activities. Cyproterone binds the androgen receptor (AR), thereby preventing androgen-induced receptor activation in target tissues and inhibiting the growth of testosterone-sensitive tumor cells. This agent also exerts progestational agonist properties at the level of the pituitary that reduce luteinizin and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH) which works in a similar fashion as Casodex) analogue plus 200mg of CPA daily during induction. Patients randomized to the intermittent arm ceased treatment, while those randomised to the continuous arm received 200mg of CPA daily plus an LHRH analogue.

The trial’s primary outcome measurement was time to subjective or objective progression. Secondary outcomes were survival and quality of life (QoL). Time off therapy in the intermittent arm was also recorded.

One hundred twenty seven (127) patients from the intermittent arm and one hundred and seven (107) patients from the continuous arm experienced disease progression, with a hazard ratio (HR) of 0.81 (95% confidence interval

[CI]: 0.63-1.05, p=0.11). There was no difference in survival, with an HR of 0.99 (95% CI: 0.80-1.23) and 170 deaths in the intermittent arm and 169 deaths in the continuous arm. The greater number of cancer deaths in the intermittent treatment arm (106 vs 84) was balanced by a greater number of cardiovascular deaths in the continuous arm (52 vs 41).

Side-effects were more pronounced in the continuous arm. Men treated with intermittent therapy reported better sexual function. Median time off therapy for the intermittent patients was 52 wk (95% CI: 39.4-65.7).

The conclusions of the researchers was that IHT should be considered for use in routine practice because it is associated with no reduction in survival, no clinically meaningful impairment in QoL, better sexual activity, and considerable economic benefit to the individual and the community.

My personal experience is clearly consistent with the findings of this trial.

Eur Urol. 2009 Feb 21. Epub ahead of print.
doi:10.1016/j.eururo.2009.02.016 Calais da Silva FE, Bono AV, Whelan P, Brausi M, Marques Queimadelos A, Martin JA, Kirkali Z, Calais da Silva FM, Robertson C
PubMed Abstract

Joel T Nowak MA, MSW