New study below.
Some may recall that I'm in favor of shutting off all escape paths while on ADT - e.g. via Zytiga, Casodex, Simvastatin & Avodart. If you are closing the door, close the windows too.
The conventional view is that since 5alpha-reductase converts testosterone [T] to dihtdrotestosterone [DHT], castrate T = castrate DHT.
I had read a paper on PCa cells finding an alternate DHT path that did not involve T. So I was very interested when Dr. Myers posted on the subject. But, as I recall, the focus of the post seitched to natural over-producers of DHT. Myers himself is one, and a small minority of his patients fail to achieve castrate DHT when placed on ADT.
Myers thought it irresponsible for doctors not to test DHT levels. He said that T was not the problem - DHT was the hormone we needed to control.
Myers' target for DHT was <=5 pg/mL. He prescribed Avodart, if necessary - quite often, only low doses (e.g. 1 cap/week) were needed.
IMO, the post didn't adequately address the issue of PCa cells escaping ADT by manufacturing DHT via an alternate path. Unless there was leakage from the cells, what value would a DHT blood test have? And such a test would have to be repeated periodically to detect ADT resistance involving DHT.
The new study is an eye-opener.
"Between 2010 and 2013, CRPC was diagnosed in 41 patients at the Tokyo Metropolitan Tama Medical Center. Following diagnosis, the patients received 0.5 mg dutasteride daily. The patients' median age was 77.3 years (range, 63-90). Bone metastases were recognized in 12 patients. All the patients received dexamethasone."
"Twenty-four (59%) patients had previously undergone chemotherapy, while 11 (27%) received docetaxel, and 24 (59%) estramustine."
"The prostatic-specific antigen (PSA) level declined in 17 (41%) patients from the baseline value, following dutasteride treatment. The median value for the PSA decrease was 23% (range, 4.3-89.8%), and the median duration of the response was 4 months (range, 1-10)."
"The PSA response rate (defined as >50% decline in PSA from the baseline value) was recognized in 7 (17%) patients. The median duration of the response was 3 months (range, 2-10)."
"Dutasteride was efficacious against CRPC in certain patients and may be a promising option in CRPC treatment."
The extent of the PSA declines (which the authors attribute to dutasteride), suggests that the DHT escape route is not uncommon.
The FDA has approved Dutasteride for BPH - not for PCa - so it is somewhat amusing to see it used for CRPC in this instance.
If Avodart were to be prescribed at an earlier stage, perhaps CRPC might be significantly delayed in those men who were destined for the DHT escape path?
So, what's next for these researchers? Perhaps Simvastatin for CRPC cases that have failed Avodart? Just kidding.
-Patrick
ncbi.nlm.nih.gov/pubmed/293...
Mol Clin Oncol. 2018 Jan;8(1):133-136. doi: 10.3892/mco.2017.1480. Epub 2017 Nov 2.
Effect of dutasteride on castration-resistant prostate cancer.
Azuma T1, Matayoshi Y1, Sato Y1, Nagase Y1.
Author information
1
Department of Urology, Tokyo Metropolitan Tama Medical Center, Fuchu, Tokyo 183-0042, Japan.
Abstract
It has previously been demonstrated that the intratumoral generation of the potent androgen dihydrotestosterone (DHT), contributes critically to the progression of prostate cancer and its castration-resistant form, castration-resistant prostate cancer (CRPC). Circulating testosterone is converted into DHT by 5α-reductase (SRD5A). Dutasteride is a dual inhibitor of type I and II SRD5A. The present study assessed the effectiveness of dutasteride in the treatment of CRPC. Between 2010 and 2013, CRPC was diagnosed in 41 patients at the Tokyo Metropolitan Tama Medical Center. Following diagnosis, the patients received 0.5 mg dutasteride daily. The patients' median age was 77.3 years (range, 63-90). Bone metastases were recognized in 12 patients. All the patients received dexamethasone. Twenty-four (59%) patients had previously undergone chemotherapy, while 11 (27%) received docetaxel, and 24 (59%) estramustine. The prostatic-specific antigen (PSA) level declined in 17 (41%) patients from the baseline value, following dutasteride treatment. The median value for the PSA decrease was 23% (range, 4.3-89.8%), and the median duration of the response was 4 months (range, 1-10). The PSA response rate (defined as >50% decline in PSA from the baseline value) was recognized in 7 (17%) patients. The median duration of the response was 3 months (range, 2-10). Dutasteride was efficacious against CRPC in certain patients and may be a promising option in CRPC treatment. A prospective randomized trial is necessary to verify the efficacy of dutasteride.
KEYWORDS:
castration-resistant prostate cancer; dutasteride; prostate cancer
PMID: 29387405 PMCID: PMC5769310 DOI: 10.3892/mco.2017.1480
Anyone taking Avodart (Dutasteride) as your only form of ADT?
