How does Lynparza work?

[Ian99]

I am brca2+ and 3 months into Lynparza. Stopped Zytiga, continuing ADT. I generally tolerate meds ok, but am finding this one v toxic.

As I understand it, the brca2 gene mutation is in all cells, not just cancerous ones. In this case, Lynparza could be preventing parp from getting to healthy cells to repair DNA; and could explain the continual SEs. PSA steady, awaiting scan results, don’t want to give up.

Can anyone enlighten me re how this drug works, especially re healthy cells. Am still on full dosage (600mg/day).

[mrscruffy]

Can't give specifics of how it works but can tell you that it does work and it started working pretty quickly. White and red blood cell counts were pretty low and oxygen exchange was rough. Lowered dose to 450mg a day and helped remediate the breathing issues while still effective. I see my MO in two weeks and will ask if I can do 300mg dose and see what happens. After dose corrected this drug has been good to me.

[Ian99 in reply to mrscruffy]

Thanks for that. My red cell count is now mild anaemic. White cells low. By oxygen exchange, do you mean tight chest and breathlessness? - I have this. When you say it works, can you quantify.. eg PSA drop, no radiographic growth, etc. I take away that a dosage reduction helped you live with it.

[mrscruffy in reply to Ian99]

Out of breath when doing simple jobs like planting a tree. Easier now but wife still makes me hire landscaper or handyman for jobs she deems too strenuous for me. No growth in mets nor are there any new mets. My PSA went from about 5.1 to 3.0 in a month's time on half dose then .31 on full dose. now hovers between .14 and .69. I test every 6 weeks

[Ian99 in reply to mrscruffy]

Seriously good results indeed. Bravo. Keep it up.

[Tall_Allen]

You are correct that it prevents self-repair of mistakes in DNA. Its toxicity (anemia, nausea, etc.) is because it isn't specific enough. The new PARP1-specific inhibitors in trials now seem to be a lot less toxic.

[Ian99 in reply to Tall_Allen]

Thanks for confirming. I would be interested to understand how the parp1 version can target only PCa cells. Pluvicto has a similar issue when targeting PSMA-avid cells, some of which are healthy eg salivary.

[j-o-h-n]

I starta my new 2024 Lynparza with a button, no more key. I makea my Maria cleana da car once a week.

Good Luck, Good Health and Good Humor.

j-o-h-n

[Ian99 in reply to j-o-h-n]

Haha. Molto divertente!

[j-o-h-n]

Grazie....

Good Luck, Good Health and Good Humor.

j-o-h-n