Timing is everything with docetaxel (and hormone therapy and probably with immunotherapy and radiopharmaceuticals too)

[Tall_Allen]

Many patients want to "be aggressive" and use medicines like docetaxel early; many patients want to put it off as long as possible. In this article, I looked at the evidence for when the "sweet spot" occurs. It also looks at optimal timing for first and second-line hormonal therapy, immunotherapy and radiopharmaceuticals. Prostate cancer is a moving target because it mutates, and therapies that work well in one stage of its evolution may not work well at another stage.

pcnrv.blogspot.com/2019/02/...

[TWTJr]

Thanks TA for the excellent article.

[lincolnj8]

Thank you. Great article. Covers a lot of ground. Early use of Zytiga discussion very helpful and encouraging.

[Ahk1]

TA,

This is from your blog:

“However, an early analysis of the TOAD randomized clinical trial suggests that using androgen ablation on men who are recurrent after prostatectomy but not yet detectably metastatic may have a net survival benefit over the selective pressure it exerts towards castration resistance. In fact, men who started on ADT earlier developed castration resistance significantly later. This effect was also noted in the TROG 03.04 RADAR trial. The authors wrote, "The cumulative incidence of transition to castration resistance was significantly lower in men receiving [longer term ADT with their EBRT]."

TA,

I am struggling to make this decision. I just had yesterday a bone scan and ct scans with no Mets found. Dr Morris wanted me to start ADT 6 months ago and I have not done it. If I read your blog correctly, the trials suggest that I better start now than later? Is this true please?

Thank you

[j-o-h-n in reply to Ahk1]

Is that Dr. Michael Morris at Sloan?

Good Luck, Good Health and Good Humor.

j-o-h-n Tuesday 02/05/2019 7:18 PM EST

[Ahk1 in reply to j-o-h-n]

Yes

[j-o-h-n in reply to Ahk1]

He is my Oncologist... Extremely compliment....

Good Luck, Good Health and Good Humor.

j-o-h-n Wednesday 02/06/2019 2:05 PM EST

[Ahk1 in reply to j-o-h-n]

I know he is and he wanted me to start ADT in August and I didn’t do it. He didn’t put any emphasis on finding/treating oligometastatic approach. I am seeing him soon. I will do what he suggests

[Tall_Allen]

Why would you NOT take Dr Morris's advice?

[Ahk1 in reply to Tall_Allen]

TA

a few reasons :

1. The trial you cited from what i understand did not say what it means by “earlier?” Is it possible we can define earlier and at what psa range is considered early

2. Too many available options which distract me and being afraid to make the wrong decision

3. Can I use tE2 instead and try to slow the psa rise for a bit before starting ADT. RonRon and others had good success with it

4. can I use casodex ( light form of ADT, may be that will work to delay the start of full blown ADT. some folks here had good success with it too

5. I am going to do the NIH test 18F decfpyl in a couple of weeks and thinking if they find a met here or there then may be I will use targeted radiation to treat( this option ofcourse would require me to do ADT with the radiation which I will certainly start ADT then)

I know I have to start ADT soon and I will but “WHEN” is a very hazy time to determine when my psa is

.51 at the moment

Thanks as always for your insight and support.

[Tall_Allen in reply to Ahk1]

1. Are you talking about TOAD? If so, they did define earlier as at the first sign of biochemical recurrence (confirmed 0.2)

2. You can only choose from what you know at the time. Without definitive info, there is no such thing as a "right' choice, only what seems best for you given what you know.

3. Estrogen shuts down production of testosterone, so it IS ADT.

4. casodex (in varying doses), estrogen patches, and intermittent ADT are certainly all possible options; so are aggressive forms of ADT (Lupron, Lupron+Casodex, Lupron+Zytiga (on a clinical trial), continuous ADT. it depends on your comfort level. All are good options to discuss with Dr Morris.

5. Assuming it is safe, of course.

[Schwah]

As always you explain complex issues clearly and concisely with article and studies to back it up. Thank you TA

Schwah

[traveller64]

Allen, excellent article as usual. Much appreciated

[cigafred]

Really appreciate this summary of the implications of a great deal of data.

[henukit]

Great analysis. Thanks Allen.

[Portugal-2]

You are amazing TA! God bless you for all your support in all our lives!

[tallguy2]

This is excellent, thank you!

[This is the same article that appears in "Prostate Cancer News, Reviews and Views." Thanks for doing this, too. I am glad to be a subscriber.]

It seems that I don't quite fit any of the models or trials discussed: by chance I found that I have mets, while still hormone-sensitive. Few of my fellow patients get this information until their PSA starts to accelerate upwards while on ADT. Bone scans are then used. They showed nothing in my case. And they still show nothing. Most urologists stop there, like they did with my father. Thanks to the CT and PET/Axumin I could take early action. I decided to hit it with chemo first while staying on ADT and then I chose a second round of IBRT on new lymph nodes and bone mets (no areas were previously subject to IBRT), despite the lack of prospective trial results showing any benefit. I am blessed with insurance that has paid for every treatment thus far.

Q: do you think I am missing anything at this point, Tall_Allen?

[Tall_Allen]

Here's what we know about mHSPC:

pcnrv.blogspot.com/2017/06/...

I'm not a fan of playing whack-a-mole with pelvic lymph nodes. Where there are some that Axumin could see, there are probably a lot more that are too small.

[tallguy2 in reply to Tall_Allen]

Thanks, and yes, that's why my radiation oncologist lit up an entire field that was not irradiated in 2012, not just the lymph nodes and bone mets that PET/Axumin revealed after chemo. Plus there can be false positives with PET/Axumin. Anyway, perhaps this will delay a third visit to radiation oncology, which I would appreciate.

I am N1, so still off the charts, as they say. Fertile ground for research. The reason that only 3% of men are newly diagnosed with hormone-sensitive, mPCA is that doctors don't know how to intercept it earlier, or don't look for it earlier. Not their fault, but this should be an area of research. Waiting for the PSA to hit 4.0 and then taking action didn't work so well for me.

[Tall_Allen in reply to tallguy2]

I agree that there are gaps in the research - but it is difficult to recruit for clinical trials in your exact situation. If anyone can do it, MD Anderson can.

[Hidden]

TA, thanks for the article! It confirms for me that my oncologist has me on the right treatment at the right time, I have two more rounds of docetaxek and I am on a 30 day dose of Lupron.

I have not read much concerning dropping Lupron for another treatment. Would that only happen after you become hormone resistant? My other question for the group is do we have examples from the group as to the average length of time it takes for the pc to go from lymph nodes to bones? I know that everyone is on the own timeline, but I cannot find much information concerning the progression from Lymph nodes.

[Tall_Allen in reply to Hidden]

You would only drop Lupron for something else if it fails to keep your testosterone low, which would be unusual. You continue with Lupron and add to it the second line hormone therapies after castration resistance.

Sometimes the cancer never goes to the bone (M1a); sometimes it is only in the bones (M1b); sometimes it is only in visceral organs - e.g., lung or liver (M1c); sometimes it is mixed from the start.

[Hidden in reply to Tall_Allen]

Thanks TA! I was hoping there had been some studies that would give me an average length of time for progression. I have been on Lupron for over 18 month and I understand that on average that we become resistant around 18 to 24 months. What would an average progression from lymph nodes to bones? I just cannot locate any studies on this. My pc has been very aggressive from before my surgery to now. Hopefully the combo of chemo and Lupron keeps my PSA low for 6-12 months. Thanks!

[TNCanuck]

Thank you.

[DaughterOnAMission]

Hi Allen, read your paper. He started with Zytiga and Lupron in mid 2018, we waited on Docetaxel. He just finished radiation, 28 sessions... with severe leg pain that started at the end of radiation. We have been told its possibly muscle degeneration by a doctor at UCLA. My dad thinks radiation did it which is unlikely. But the timing was strange.

We are thinking of starting Xtandi now although his PSA is .1. He is still responding to Zytiga... but with switching up doses to nighttime, reducing doses... nothing is helping. Hes losing the ability to walk because of Zytiga.

Should he do Xtandi next or Docetaxel? Sounds like both would be effective. But now his WBC and RBCs are lower than ever so I'm worried about chemo.

He can't escape the muscle pain. Comes and goes every day, but during a test where the doctor suggested being off for a week, the pain lessened.

Looking for help because we may be in the sweet spot you mentioned.

[Tall_Allen in reply to DaughterOnAMission]

I doubt that his leg pain has anything to do with prostate radiation. Is he taking a statin? He has no detectable metastases in his femur? Does he exercise? Maybe muscle rehab is needed?

[DaughterOnAMission in reply to Tall_Allen]

Yes hes taking Lipitor, no Mets anywhere but in lumbar. Small ones. He was just shoveling dirt for hours the other day.... on one of his good days. He walks everyday. Just seems there may be muscle breakdown from zytiga since switching times changed the pain. Ehsts next in this weird situation? It comes and goes. Off zytiga its better.

[Tall_Allen in reply to DaughterOnAMission]

It may be the Lipitor. Myopathy is a very common side effect. If he is taking it for CV health, he might want to talk to his cardiologist about alternatives.