Finasteride, PSA doubling time, and intermittent hormone therapy

For years, some clinicians have been telling their patients to use a 5α-reductase inhibitors (5-ARIs) like finasteride or dutasteride as a form of “bridge” therapy to extend their periods of time off primary hormone therapy while being treated with intermittent hormone therapy or IHT.

The problem has always been that there are very few clinical data to support this recommendation, and there are still very few, but a new paper by Locke and Bruchovsky has added somewhat to our knowledge.

Although there are data suggesting the value of 5-ARIs in management of patients on IHT, it has been far from clear how the 5-ARIs might be producing this effect. In the present study, Locke and Bruchovsky followed just six patients who were being treated with IHT for periods of between 7 and 10 years. They conducted PSA tests in each of the six patients on a monthly basis throughout at least one off cycle of IHT, and used these data to calculate the patients’ PSA doubling times during these off cycles.

Based on these data, they make the following assertions:

  • That administration of finasteride was associated with a reduction in the rate of increase of serum PSA in the off-treatment period of any given cycle within a sequence of 5 cycles in total.
  • In a total of 15 cycles, finasteride extended PSA doubling time from a mean of 7.7 weeks (n = 11, range, 2.3 to 29.8 weeks) to a mean of 45.1 weeks (n = 6; range, 13.8 to 99.7 weeks).
  • One patient was characterized by an apparent pseudo-resistance to finasteride in the second cycle of treatment.
  • Another patient was characterized by complete resistance to finasteride in the fourth cycle of treatment.

They conclude that, “Finasteride can be introduced into any cycle of intermittent androgen suppression with the expectation of an extension of PSA doubling time.”

Now The “New” Prostate Cancer InfoLink would like to be able to clarify the value of 5-ARIs in the off-hormone periods of IHT as much as the next guy, and we do find Locke and Bruchovsky’s data interesting. But we have a hard time with their conclusion — which all but suggests that every patient on IHT should be receiving finasteride during every off-homone period: 

  • This is a tiny study, in which the patients appear to have been used as their own controls, but what is the standard baseline against we are comparing the PSA doubling time while the patients were on only finasteride.
  • The range of the PSA doubling times observed among these 6 patients is huge; to claim that finasteride therapy extended the mean PSA doubling time from 7.7 weeks to nearly a year based only on these data seems to be a tad assertive.
  • The abstract of the paper gives us no information to suggest that all six patients were receiving the same form of hormone therapy, that they had started out with similar clinical profiles, and that there were no other significant differences between them.

So, for The “New” Prostate Cancer InfoLink, this paper provides a tiny amount of additional information that is suggestive for a role for 5-ARIs in IHT, but we would like to see a far more robust set of data before we would want to draw the conclusion offered by Locke and Buchovsky.

10 Responses

  1. WOW!


    Thank you so much for publishing this very encouraging study! It certainly is in line with the earlier study by Scholz, Lam, Strum and team regarding finasteride as maintenance for triple blockade compared to patients in their practice on double blockade without finasteride. My impression from paying attention to experts in hormonal blockade is that lower risk patients get a huge boost in doubling time, while us high risk guys get roughly a month off for each month on therapy. Hey, we’ll take that and run with it!

    It is also generally in line with my own experience, based on fairly closely following the Scholz/Lam/Strum approach, as also practiced by Dr. Myers, with Drs. Leibowitz and Tucker contributing insights from their low-risk patient base. None of these doctors, in casual comments, expected in the early years that I or patients like me would do as well as I have, based on my challenging case characteristics, but I and some others with similar cases have done very well on triple blockade with a 5-ARI drug as maintenance, supported by lifestyle tactics and often a bisphosphonate. My bottom line is that I’ve enjoyed a bit more time off therapy than on, which is no where near as good as experienced by patients with much lower risk, but I am delighted with my results.
    I realize that so many doctors are still skeptical about combined and triple blockade, with many still holding out for gold-standard type clinical trial evidence (a tragic pipedream!), but results like those reported are consistent with what we IADT3 guys see among our peers.

  2. Okay, it may be a small study, but it confirms what [some] medical oncologists specializing specifically in research and treatment of advanced prostate cancer have been saying and prescribing for years (Strum, Leibowitz, Myers, Scholz, Tucker, Tisman, Lam, and others). Possibly what works for one may not work for another, but I know of many patients who have had successful off-times while maintaining with either of the 5AR inhibitors dutasteride/Avodart or finasteride/Proscar. In my own case, I was kept on ADT2 with Lupron and Casodex for 5 years by my urologist, but during that time I began my personal research and study to determine for myself what should be the most appropriate androgen deprivation therapy. When I asked my urologist why I was kept on these drugs continuously for 5 years with a constant PSA of < 0.01 ng/ml, his only reply was "well, its working isn't it." I moved to a medical oncologist, went off the ADT2, but did NOT maintain with a 5AR inhibitor. By 2 years my PSA had risen sufficiently that I returned to ADT but this time ADT3 adding dutasteride/Avodart. PSA immediately dropped to < 0.01 ng/ml and after another year, again went off Lupron and Casodex BUT have now been "maintaining" with dutasteride/Avodart for nearing 6 YEARS! My PSA during the past 4 of my nearing 6 years has very slowly elevated to its most current 1.86 ng/ml. My personal choice will be to return to bicalutamide/generic of Casodex, but at 150 mg this time, when my PSA reaches 2.0 ng/ml (likely by the time of my next appointment in September). No need to return to Lupron or any LHRH agonist since when my urologist kept me on constant ADT2 for 5 years, my testosterone went into what I guess could be called andropause and has never returned. Latest testosterone level was 13 ng/dl. In summary, maintaining with the 5AR inhibitor dutasteride/Avodart has permitted me to remain off an LHRH agonist and antiandrogen Casodex for nearly 6 years compared to the only 2 years of my first "time-off" where I had not "maintained" with a 5AR inhibitor; sufficient evidence to this nearly 18-year prostate cancer and nearly 14-year IAD/IHT patient that a 5AR inhibitor should be an important addition to every man whose treatment must move to androgen/hormonal deprivation therapy.

  3. More important, what if anything do 5-ARIs do for survival? We know that they provide morbidity problems, so do they provide a real benefit?

  4. Well, Joel, I would expect that without the use of a 5AR inhibitor during my first “time-off” permitting me only 2 years off, but now with the use of the 5AR inhibitor dutasteride/Avodart during my current nearing 6 years “time-off,” it appears to have provided me many years of survival I may not have had without its use. I noticed that the sitemaster inserted “some” when I mentioned medical oncologists who specialize “specifically” in research and treatment of advanced prostate cancer. The medical oncologists I listed are the only ones I am aware of who “specialize specifically” in the treatment of, particularly, advanced prostate cancer. Others are involved in research that includes prostate cancer as well as other cancers, but I am not aware that they have dedicated their practice specifically to prostate cancer.

  5. Dear Chuck:

    I am very sorry, but I think that to imply that medical oncologists like Chris Logothetis, Howard Scher, Maha Hussein, Oliver Sartor, and others who spend the vast majority of their working lives doing research on and treating patients with prostate cancer (and sometimes other forms of genitourinary cancer too) do not “specialize” in the treatment of prostate cancer is somewhat ungracious to say the least. Surgeons like Peter Scardino treat patients with bladder cancer as well as prostate cancer. Are you suggesting that Dr. Scardino is not a specialist in prostate cancer surgery?

  6. I wonder why dutasteride is used when it seems that astaxanthin, a natural carotenoid, will do approximately the same thing.

    Is there any information about that?

    I am trying Casodex and Lupron with supplements of turmeric, pomegranate, maitake mushroom D-fraction, resveratrol, vitamin D, vitamin K2, palm oil tocotrienols, astaxanthin, etc. Even if the results are good, I will be unable to assign credit.

    At this time, I have been on this regime for just 3 months and have no results to report on my probably localized Gleason 7 prostate cancer.

  7. Dear Maurice:

    I am not aware of any clinical data supporting the activity of astaxanthin in the treatment of progressive prostate cancer, whereas there are at least some clinical data on the use of dutasteride.

  8. Hi Joel,

    Way back last year on July 7 you wrote:

    “More important, what if anything do 5-ARIs do for survival? We know that they provide morbidity problems, so do they provide a real benefit?”

    I meant to reply, but better late than never.

    The extended off-therapy periods are almost sure to have the effect of delaying the need for more aggressive treatment, such as second-line hormonal therapy, Provenge, chemotherapy, etc. That is a good thing in itself. It is likely, I think, that survival will be extended. While we would like to test that with an appropriate randomized, large, long clinical trial, I doubt that will ever be practical. For starters, its going to be hard to get people into the non-5-ARI group when the very common large extensions in PSA doubling time become more widely recognized.

    If you are still reading, would you mind explaining the “morbidity problems” that you are concerned about? In a small percentage of men there seems to be an adverse (but reversible) effect on libido and/or erectile function, with the vast majority of us doing just fine. There are a few other potential adverse effects but they look quite minor to me in impact and incidence. The one effect you may be thinking of is that these drugs cause the regrowth of scalp hair in the male pattern baldness areas. That tends to attract amorous females, and of course we have to spend more time fending them off, which is burdensome and can be counted as an adverse effect.

    I’ve been on finasteride continuously for nearly 11 years now during three cycles of ADT3 and two full off-therapy periods … I am currently about two-thirds of the way through the third off-therapy period.

  9. Just now noticing Sitemaster’s concern on my not identifying other physicians involved in the treatment of prostate cancer … apparently Sitemaster failed to notice my words “and others,” I certainly recognize the involvement in prostate cancer research and treatment of the physicians listed by Sitemaster, “and others” should have satisfied his concerns.

  10. Hi Joel,

    I just reread this thread due to Chuck’s posting, and I have another aspect to mention in response to your question a long time ago — hope you are still getting notice of responses.

    Joel Nowak, on July 7, 2010 at 8:25 pm said:

    “More important, what if anything do 5-ARIs do for survival? We know that they provide morbidity problems, so do they provide a real benefit?”

    My added reply: The addition of time due to use of 5-ARI drugs gives other technology and knowledge time to advance, giving us more options. Obviously, many new drugs have and are becoming available, but here is my own story. Advanced bone (NaF18 PET/CT scan) and soft tissue (feraheme USPIO MRI scan) imaging revealed that I was eligible for an attempt at curative radiation. I had 78 Gy with 46 Gy pelvic boost IMRT TomoTherapy 2 years ago, supported by my fourth round (18 months) of ADT3, plus other supportive tactics. Four PSAs (every 3 months) following the run out time for Lupron have not exceeded 0.02.

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