Dutasteride & Abiraterone. The rewrite.

[pjoshea13]

All quotes are from the papers cited in yesterday's confusing:

"Dutasteride [Avodart] & Abiraterone [Zytiga]?"

1] "Abiraterone is metabolized in patients to D4A" (Δ4-abiraterone)

2] D4A "has even greater anti-tumor activity" than Abiraterone

3] but "D4A is converted to ... 3-keto-5α-abi" (by 5alpha reductase)

4] & 3-keto-5α-abi "promotes prostate cancer progression."

5] Dutasteride prevents the conversion

6] Therefore Dutasteride might enhance (& prolong?) the effectiveness of Abiraterone

-Patrick

[NPfisherman]

Thanks Patrick....a question for my MO...next week

[Break60]

I’m surprised that TA , who says dutasteride confers no benefit, hasn’t weighed in here?

[pjoshea13 in reply to Break60]

The only published trial I have found is the Taplin study that I cited:

ncbi.nlm.nih.gov/pmc/articl...

but all of the men received Avodart.

"Our study did not directly compare the efficacy of abiraterone and dutasteride versus abiraterone alone, and comparisons with historical controls are confounded by differences in patient populations and methods."

-Patrick

[Break60 in reply to pjoshea13]

It’s hard to see any downside to avodart.

[jdm3]

Thanks for the clarification. I hope there is a LOT more D4A than 3-keto-5α-abi in the metabolic process or the use of Abiraterone would seem to be detrimental eventually.

[pjoshea13 in reply to jdm3]

Alas,

"... 3-keto-5α-abi, is more abundant than D4A in patients with prostate cancer taking abiraterone, and is an androgen receptor (AR) agonist, which promotes prostate cancer progression."

ncbi.nlm.nih.gov/pmc/articl...

-Patrick

[jdm3 in reply to pjoshea13]

Hmmm.. Thanks. I finally got around to reading the article and makes me wonder why Duasteride is not recommended with Abiraterone. I suppose the benefits of taking Abiraterone to block androgen synthesis are considered to far outweigh the possible detrimental consequences of its metabolites.

[hansjd]

Thank you Patrick for the clarification. That's what I thought your first post was saying, but it was great to have it stated so clearly and concisely. We find your posts so worthwhile. Please keep up the good work. We all benefit !

[Hidden]

Hi Patrick,

This is a timely post, because of my current research for my current state of "hormone sensitive" treatments. Although, the study targets "castrate resistant" patients, early PCa treatments can benefit, hence the SoC of adding Zytiga.

Since this was not a randomized study protocol, the treatment will be considered research for US based health insurers. Consequently, mainstream docs will not prescribe.

Although, the US cost (GoodRx) of Generic Avodart is about $14.00 for 30 capsules. I spilt my time between Boston (USA) and the Philippines, getting prescriptions off SoC is not difficult for me.

You're an Aussie, perhaps have more patient rights than US...

Anyway, I'm going to bring this up next Dana-Farber visit, since Dr Taplin is on staff, let's see what happens.

[jdm3 in reply to Hidden]

Curious to know what they say at DFCI about this. Please keep us posted. I go there at the end of February for a follow up with Dr. Sweeney. Thanks, Josh

[pjoshea13 in reply to Hidden]

I'm an Aussie? When I moved to New York from England in 1974, cab drivers assumed I was Australian too. But no. -Patrick

[monte1111]

Cab drivers in 1974 New York understood some sort of English idiom. Interesting historical fact.

[pjoshea13 in reply to monte1111]

I have fond memories of the era when Russians with insufficient English to become COBOL programmers naturally became cab drivers. I was in a cab travelling uptown from the WTC & we were at a red light at the Bowery. The light turned green & another cab raced ahead. My guy swore in Russian & gave chase. A baseball bat was produced & he began whacking the side of the other cab. All this at about 60 mph while the two drivers were yelling at each other in Russian. The other cab made a hasty left & I arrived safely at my office.

-Patrick