Avodart when off ADT a mistake?

[cigafred]

If one is trying to prevent prostate cancer cells from becoming insensitive to ADT, then is it wise to continue dutasteride while on the off cycle? If per Snuffy most of the support for PC cells comes from DHT not T, then just as stopping T reduces the DHT, is not dutasteride acting in a similar way and thus preventing the ADT holiday from resensitizing the PC cells? Obviously I have no understanding of the chemistry involved, but this seems logical to me, and the AVIAS trial showed no benefit to continuing dutasteride while on holiday.

[Tall_Allen]

Your best info is the AVIAS trial rather than what Snuffy hypothesized years ago.

[Schwah in reply to Tall_Allen]

And what was that ?

[Tall_Allen in reply to Schwah]

"This small-scale Phase II randomized controlled trial showed no benefit to the addition of dutasteride to an IAD regimen."

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

[GP24]

"preventing the ADT holiday from resensitizing the PC cells?" An ADT holiday will not resensitize the PC cells. As long as you are not castration resistant, your cells are hormone-sensitive while on ADT or while on holiday. The hope is that if you make holidays, it will take longer to make the cells insensitive to ADT (=castration resistant) than if you have continuous ADT. But trials did not show that this would happen.

If you want to make a looong holiday you can use Casodex 50 mg during the holiday instead of Lupron.

[cigafred in reply to GP24]

Thank you GP24. My point was whether it really is a holiday if one is taking dutasteride or if, because the end result--low DHT--is the same, it is not really a holiday in terms of developing castrate resistance.

[larry_dammit]

Warning. I was on Avadart for 4 years or more prior to my stage 4 diagnosis, the Avadart managed to artificially keep my PSA low while all the time my cancer was growing. Don’t take the crap 😡😡😡

[Break60 in reply to larry_dammit]

Same thing happened to me but from finasteride.

[pjoshea13]

The Avodart arm of the AVIAS trial started out with only 49 men (without mets), 17 of whom were Gleason score ≤6 cases (a third!). "88% of patients had been treated with radiotherapy and 12% with radical prostatectomy".

"Patients treated with dutasteride had a more rapid recovery of PSA and testosterone in the off-treatment interval compared to placebo".

During the IADT off-phase, testosterone [T] recovers slowly. Dr. Steve Freedland has warned that the IADT off-phase is a continuation of ADT for much of the time.

As T rises up to Morgentaler's "AR saturation" point, PSA tends to rise too. The hope is that the PSA will settle down once T has risen into the normal range. Otherwise, a speedy T recovery would result in a short off-phase.

A concern of Dr. Myers was that the off-phase be of significant duration. IADT cannot be repeated indefinitely. Often, a man gets only two cycles before developing CRPC. The point of IADT is that men get a breather from ADT - not that the cancer get a breather too. It seems prudent to inhibit DHT production IMO.

Avodart itself, as monotherapy, is not a particularly effective form of ADT. Could it accelerate CRPC? None of the men in AVIAS had CRPC at the end of the study.

Some men are excessive DHT producers. Dr. Myers is one. The aim of ADT is to deprive PCa of DHT, but castrate T does not always produce castrate DHT. In addition, resistance to ADT can lead to DHT production via a path that does not start with T. Avodart can inhibit that.

If I were on IADT, I would want to restore T at the start of the off-phase. I would also want to limit DHT production via Avodart.

-Patrick

[cigafred]

Comprehensive, succinct, to the point. Thank you Patrick.