Treating recurrence — The use of combined therapies

[Ralph Valle]

When men experience recurrence after localized treatment, is combination androden deprivation including androgen receptor blockers and 5-alpha reductase inhibitors warranted? Member experiences, please.

[Ralph Valle]

The first thing to do is recognize that although the existing evidence is not supported by randomized clinical trials, there is enough evidence that 5-AR inhibitors are useful in the treatment of prostate cancer.

What is that evidence? Here is some:

1. The PCPT trial demostrated a 25% PCa prevention benefit. The implication is that inhibiting DHT is men older than 50 can have a protective effect. Also that these inhivitors are active compounds in PCa. The increase in aggressive cancers, has been a red herring, but several explanations seem to agree that it was an artifactual finding either caused by misgrading or by enhanced detection by gland volume reduction.

2. Finasteride was developed by Merck to treat BPH. Since BPH and PCa are two diseases that could cause a PSA elevation and those prostate conditions can and do coexist in many males, Merck promoted studies known as The Finasteride Group Study to ensure that men treated with finasteride for BPH would not be at increased risk of PCa by having reduced levels of PSA. In those studies, men treated with Proscar for prostate enlargement experienced a blood serum PSA reduction of approximately 50%. There is ample evidence that this PSA reduction is related to a reduction in gland volume (maximized by one year of treatment) caused by cell death and reduced cell proliferation. In other words, the PSA reduction is not an artifact causing a masking effect on the measuring test, but simply an effect caused by definitive biological factors (gland volume reduction)induced by the inhibition of DHT.

3. In the Dominican Republic there are several families of men born with a genetic disorder by which they do not convert testosterone to dihydrotestosterone (DHT). These men all have prostate atrophy, do not experience either BPH or prostate cancer and are capable of procreation. It is a medical fact that DHT is recognized as the androgen involved in the development of the prostate gland.

4. The use of Proscar to treat prostate cancer is not a recognized label use for this product. In spite of this, Proscar is used in hormone suppression protocols when maximal suppression is intended. It is used in intermittent androgen suppression during the off-cycle period to extend the time off medications. Drs. Leibowitz, Strum/Scholz and Bruchovsky have successfully used Proscar to effectively extend the off-cycle period.

5. Dr. William Fair studied the use of Proscar in treating stage D PCa and concluded that a decrease inserum PSA in the finasteride treatment group
suggests that finasteride exerts a minor effect in patients with prostate cancer. This effect does not approach that seen with medical or surgical castration, but it is important because finasteride's lack of toxicity.

6. E Damber and coworkers in Sweden showed that finasteride treatment decreases VEGF expression in the human prostate. Vascular endothelial growth factor (VEGF) is a potent regulatory factor of angiogenesis in human prostate tissue. Also Wang and coworkers at New York University demonstrated that the level of androgen receptor was dramatically decreased in the cells treated with finasteride.

7. In hematuria cases caused by a TURP procedures, finasteride has been proven effective in reducing or preventing the event by reducing the flow of blood to the prostate. Also in bleeding caused by radiation treatment, finasteride is effective in managing this complication. Finasteride's action in reducing blood flow to prostate tissues indicates that the action mechanism is antiangiogenic and explains its value in promoting longer off-cycle periods in an intermittent hormonal suppression protocol.

In summary, Proscar and Avodart have a place in the treatment of PCa. These drugs are a milder form of hormone suppression and yet have an important place in this treatment. The major benefit being the prolongation of hormone suppression off-cycles that is an improvement in patient's quality of life. In patients diagnosed with PCa there is no need to double PSA when using these inhibitors. This is because these inhibitors have an effect on PCa tumor cells by inducing cell death and the PSA level is a true measurement of their disease.

The answer to questions raised about the use of 5AR inhibitors in the treatment and off-cycle maintenance in the treatment of PCa depends on the trigger point pre-decided by the patient. There is no artificial masking of PSA. There is no need to double PSA level. The patient decides when to restart treatment, when using a 5-AR inhibitor in an off-cycle maintenance when PSA has reached the trigger point. This, with the certainty that the off-cycle maintenance is acting on the cancer as supported by the above references.


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[Ralph Valle]

I often wonder how many of the group had hormone treatment and if the treatment has been continuous or intermittent. It would be interesting to know if the side effects of treatment are permanent or if they improve on intermittent while this protocol maintains cancer control.

[Lenny Hirsch]

Ralph

Since 2002 I have been on IHT, Casodex and Proscar. Changed Proscar to Avodart around 2005. My first on period was for a year with the psa at UD.The first off period was for three and half years when my psa reached 5.01. I stopped the prostcar as it was effecting my sexual function. At the moment I am taking Casodex 150mg and Avodart. The PSA has been holding steady at 0.2.
In another three months I hope to stop the Casodex and will continue with the Avodart. I am thinking of cutting down on the Avodart to alternative days to see what effect it will have on the psa and on ED. Over this entire period the only side effects were tender and enlarged breasts and a certain amount of ED. The breast story I solved with Tamoxifen 20mg for a month. Since RP there has been slight ED, but the taking of Proscar and then Avodart definitely has made life more difficult, but Cialis etc corrects this problems.

I recommend this protocol to those who are interested in a good QOL and are not afraid to take on the cancer on their terms. I know that when this route fails I can still call in the heavy artillery and go onto Triple Hormone Block. I am now 12 years after diagnoses.

[Ralph Valle]

Thanks Lenny for sharing your treatment protocol. Some of the evidence based medical world does not share the use of combined therapies. Little by little, those telling their patients "Proscar or Avodart are for BPH only" might be changing their views as more research is done. I have seen results similar to yours at the support group level. This is only anecdotal, but if it works, why not benefit from it while science proves or disproves the point.