Prazosin vs. Doxazosin for Prostate Cancer Inhibition

[MateoBeach]

 There is pretty good preclinical as well as some clinical evidence in Prostate cancer patients that two of the Alpha1 receptor blockers, give improved outcomes in terms of prostate cancer recurrence, progression and even metastasis. The two specific drugs with the strongest evidence are Prazosin and Doxazosin. Both are available generics and both are commonly prescribed for high blood pressure as well as for helping with urinary flow from BPH. This is by means of their primary action of relaxing smooth muscle fibers in blood vessel walls and in the urethra.

But they have multiple other cellular and signaling actions that are likely contributing to their anti-prostate cancer effects. I currently take high blood pressure medications and am not seeing good control. So I plan to switch out one and start either Doxazosin or Prazosin. It is not clear to me which is better since I cannot find them in a trial head-to-head.

Dosing is similar and both require starting very low for the first days then titrating up. Here is some of the research. The first link is a very good review of the mechanisms implicated for prostate cancer. 

The role of alpha-blockers in the management of prostate cancer

pubmed.ncbi.nlm.nih.gov/151... 

And here is a study (retrospective) of recurrence rates of PC after initial RT. (Thanks to Scout for initially posting this.)

A Pilot retrospective analysis of alpha-blockers on recurrence in men with localised prostate cancer treated

nature.com/articles/s41598-...

 "Prazosin significantly reduced biochemical relapse at both two and five-years (2.72%, 8.84%) compared to control (22.61%, 34.52%). Recurrence free survival was also significantly higher in the prazosin group. This remained after multivariable analysis (HR: 0.09, 95% CI: 0.04–0.26, p < 0.001). Patients receiving prazosin had a 3.9 times lower relative risk of biochemical relapse compared to control." 

And an abstract from ASCO on reduction of metastasis 14.4% vs 7.4% over 15 years: 

Doxazosin use in prostate cancer patients: Its effect on development of metastases.

ascopubs.org/doi/abs/10.120... 

"Results: Of the 941 patients identified with prostate cancer, 121 met the criteria for doxazosin use. Of the 121 patients who used doxazosin, 9 developed metastases (7.4%). Of the 785 patients who did not use doxazosin, 113 developed metastases (14.4%). This difference met statistical significance (p < 0.05). Conclusions: Through stimulation of the EphA2 tyrosine kinase, doxazosin has been shown to decrease the ability of prostate cancer cells to metastasize in an orthotopic xenograft model of human prostate cancer cells5. A 15 year single institution study of prostate cancer patients suggests that doxazosin use was associated with a significantly decreased rate of prostate cancer metastasis."  

[Scout4answers]

Good article.

I have been taking Prazosin for several months for these very properties.

[gsun]

Does it reduce the spread of mets if you are already metastatic?

[MateoBeach in reply to gsun]

perhaps it can be helpful in reducing further growth and spread. See Smurtaw reply for his links, especially his first one.

[gsun in reply to MateoBeach]

Unfortunately, I'm not are search scientist and 90% of these reports go over my head. I usually do get the gist of it though.I will go over this with my MO next month.

[Spyder54]

significantly better relapse rates at 2 yrs and 5 yrs. Thanks again Paul, and Scout.

[BruceSF]

I've been taking prazosin for about 4 years now, following HDR brachytherapy and ebrt with WPR for Gleason 9 with 10 invaded lymph nodes detected by PSMA/PET. I had 2 years of lupron and Zytiga, and my psa has been <0.02 since nadir (it was undetectable until June 2022 and I had readings of .017, undetectable and .016 since then).

Currently I take flomax in the morning and 2 mg prazosin at bedtime. I had been taking 2 mg prazosin both in the morning and evening but I developed a urinary tract infection a year ago and I switched to flomax in the morning. I had mild high blood pressure while taking the Zytiga, so the prazosin was ok'ed by my cardiologist just for that reason (though I requested it since I had read the articles about its efficacy in deterring progression).

So, I'm just an N=1 sample, but I'm very happy with the results so far!

Bruce

[Scout4answers in reply to BruceSF]

Credit to Bruce SF for originality bringing this up and sending me down this path.

[Scout4answers in reply to Scout4answers]

also changed Statin to Pitavastatin for same anti PCa characteristics. Both are low risk moves that MAY give me an edge over progression of PCa

[MateoBeach]

You are the BEST in assembling research, Russ! Thank you. The last two references show mechanisms of action against PC cell lines from doxazosin but not compared with prazosin. Looks like the only direct comparison is in your first reference which did compare the two, and it clearly favors prazosin over doxazosin. And, yes there is implication for some synergy with BAT. 👍🙏

[cigafred]

More great work, many thanks.

[Cooolone]

BAT is so compelling as it has been expanded by practicioners that I'm finding it interesting and yet hard to understand why it is not more mainstream...

Thank you for posting!

[Cooolone]

Awesome info and definitely another Save As PDF for the links and research you've done! Lot's of reading this week

Thank you

[Purple-Bike]

Indeed there is a decent chance prazosin could be quite beneficial, maybe even a game changer.

For me it's the no 1 supplement and the only one I never miss, unless I am forced to because of my diastolic dropping too low. Below 60 for much of the time may be dangerous for the heart. So I need to go even lower than Russ, 0.5 to 1 mg daily, am still learning to calibrate but fear I will wind up closer to the lower range. The dose was 1-2 mg in the study comparing prazosin with tamsulosin and controls.

Am looking for a side free way to up diastolic but this is probably a hopeless search.