Casodex monotherapy after biochemical recurrence for pt3b

From everything I've read, there are more side effects with Casodex than with GnRH agonists or antagonists, although your dose (50 mg) is low. In particular, gynecomastia (man boobs) is a particular problem with Casodex that can be prevented with 10 mg/day of tamoxifen.

If and when Casodex fails, will other drugs like Lupron work?

Stopping testosterone production with drugs like Lupron (GnRH agonists) or castration will continue to be beneficial even after Casodex is no longer able to block (and may even feed) the androgen receptor.

Is it possible that Casodex monotherapy may shorten the time to castrate resistant disease?

Casodex will sometimes have a paradoxical effect on the androgen receptor with long use, activating it rather than blocking it. There is a lot of controversy about when to start lifelong ADT of any kind because of the cumulative nature of SEs over time and the selective pressure on the cancer. Everyone agrees that it's a good idea when there are symptoms, metastases, very high PSA or very rapid PSA doubling time. Beyond that there's no consensus.

- Allen

Either way, you are preventing testosterone from activating testosterone-activated cells of all kinds, cancerous as well as healthy cells used for normal functioning (e.g., brains, muscle, bone, etc.). That's why there are such side effects as mood swings, libido loss, lean tissue loss, and bone loss with either. However, with Casodex, there is plenty of testosterone in circulation. When testosterone isn't used, it's metabolized to either DHT (a more powerful androgen) or estrogen. Estrogen is what is responsible for the extra SEs we see with Casodex, like gynecomastia, fat accumulation, and possibly CV SEs.

- Allen

Thanks for those references. My source is a meta-analysis of all 11 studies undertaken up to 2013 (n=3,060) on the subject. They conclude:

"Currently available evidence suggests that use of non-steroidal antiandrogen monotherapy compared with medical or surgical castration monotherapy for advanced prostate cancer is less effective in terms of overall survival, clinical progression, treatment failure and treatment discontinuation due to adverse events. "

onlinelibrary.wiley.com/doi/10.1002/14651858.CD009266.pub2/abstract

Gynecomastia is worse with Casodex; hot flashes are worse with castration.

So I don't see the benefit of Casodex monotherapy if it is less effective and more patients discontinue treatment due to its side effects. However, other anti-androgens - Xtandi or ARN-509 - are probably more effective, but their use as monotherapies has not yet been proven.

- Allen

Call me paranoid or call me a skeptic or call me crazy, but I also want to acknowledge the gut feeling I have that medical professionals are intentionally ignoring Casodex monotherapy. Could it be based on the fact that Casodex is dirt cheap in comparison to Lupron and the like?

Peanut,
My MO is a very well known expert in the US in treatment of advanced pc.

Traveler,

Thanks for posting this and the JCO link above. My RO put me on Casodex for 3 months during my SRT (50 mg). Both my RO and my uro have suggested going to Casodex monotherapy at some point in the future if my PSA continues to rise. My PSA has now held steady since April, so there may be no need to consider doing anything for quite a while. If it comes time to consider further treatment I will first consult with an MO before deciding what route to take. But I'm filing away your and Tall Allen's comments here for future consideration.
Jim

Traveller58

Your story is of interest to me and I thank you for posting it. I am interested in the details regarding the bicalutamide as a monotherapy.
Somehow we have similar treatment outcomes with a case of recurrence after failed RP and SRT. We both are now on ADT as systemic patients but in my case I opted initially for monotherapy with a LHRH agonist. My doctor’s protocol is to administer ADT intermittently (on/off periods) because it allows verifying possible “cure” (via unmasked PSA) and it provides a period free from the risks and side effects of the treatment. It also provides the possibility in obtaining a positive image study if the PSA increases to levels above 1.5 ng/ml.

So far I have managed to be off drugs since 2012 when the 6-month Eligard shot of Nov 2011 lost its effectiveness by May 2012. This period will end when the PSA reaches the trigger threshold of 2.0 ng/ml. At that time I will restart ADT however, I would like to do it in a monotherapy with an antiandrogen alone.

My experience with Eligard (leuprolide acetate) was not that bad. During castration (18 months) I experienced numerous side effects but mild. Fatigue was the worse. Probably I was not affected as many guys report because of my tactics involving compulsive physical exercises, nutrition and a change in life style (earlier dinners, afternoon naps, etc).
Since the “ware off” of Eligard, the PSA climbed steadily in the beginning (accompanying the increase of the testosterone to normal levels at 400), from a two years low of 0.02 ng/ml (till Aug 2012) to PSA= 1.20 by May 2014. From there it slowed the pace reaching the present level of PSA= 1.46. Overall its PSADT equals to 9.5 months, but in the past 18 months the doubling corresponds to a “sluggish” 76 months (6.3 years). I cannot estimate on a date when I will have to restart ADT.

Meanwhile, I become interested in procuring still “cure” with the so called oligometastatic approach. This starts with a PET/MRI image exam using 68ga PSMA technique to detect and locate the metastases. I am waiting for an increase of the PSA close to 2.0 ng/ml level to submit to the test. This must be done before starting ADT. If the image study is successful (positive), I would then proceed to a sort of spot radiation of those oligometastases, instead of ADT. Otherwise I would restart ADT but this time with bicalutamide alone if my doctor “permits”. Tall Allen has help me before in understanding the procedure.

You can try the same goal and still look for cure or you can wait till becoming refractory. ADT can be administered at any level of PSA.

Best wishes and luck in your journey.

Baptista

Traveller

Back in 2000 tools and techniques to diagnose PCa were not as extensive as it is today. The contrast agents for image studies in PCa cases were also not as “sophisticated”. The parameters used by doctors to diagnose a clinical stage were pretty basic and suggestive. Micrometastases (as the term suggests) were not detected by image but would be the status attributed to a case when under the microscope the cancerous cells were seen not forming a sort of “encapsulate” tumour. Instead these would group in sort of spread colonies. The diagnosis was given to me by a medical oncologist at MSKCC (Slovin) who reviewed the data on my case including the prostate specimens from RP. It was also designated by my urologist/surgeon and a famous HDR radiologist I consulted when looking for SRT in 2001.

In fact micrometastases are difficult to “catch” with simple directional radiation (IMRT). I believe that at present times, most probably I would have been recommended to a salvage treatment with a combination therapy of Chemo plus RT.
Gleason 5 at the time was rare and later (2005) was abolished by the urological associations around the world, upgrading it to Gs6 (3+3). Before RP, DRE was negative but the sextant biopsy (typical at the time) indicated voluminous cancer in all needles, but no tertiary. The still “travelling” cancerous cells in my system may have a different Gleason grade. I do not know which type is living or where it is hiding, but it seems not to be aggressive. Prostate size at RP was normal at 25cc (14 grams) and no BPH were identified.

Regarding statistics of image exams, the PSMA PET has PSA level limitations in identifying PCa. It seems that the probability for positive exams is higher at higher levels of PSA. Lower levels risk false negatives, which is not the preferable scenario for an oligometastatic treatment. I need those positive targets for the spot radiation.
Against the odds, my present uro-oncologist does not recommend this oligo approach to micrometastases cases. He says that those spots will continuously turn detectable as they grow in size along one’s journey. What is not identified by the PET today will be identified latter and rads should not over pass the absorbing limits of tissues. In other words, rads over rads are not recommendable.

I wonder about your “decreasing testosterone” statement. Does Casodex influence the level of circulating testosterone?
In the past 12 months my testosterone has also decreased a lot (400 to 200) but I though it to be a cause for the increase in estradiol (produced from testosterone) around my waist and most probably due to gynecomastia.

Best
Baptista