Connect
← Return to Tumor can’t be removed: What are chances of survival now?
Discussion
Tumor can’t be removed: What are chances of survival now?
Pancreatic Cancer | Last Active: Dec 28, 2023 | Replies (38)Comment receiving replies
@pendesk8 , like you, I also don't understand why the PARP inhibitor is not given in conjunction with something else.
My understanding is that the PARP inhibitors prevent cancer cells from _repairing_ damaged DNA, while the traditional cytotoxic drugs (Folfirinox, GAC, etc) _cause_ the kind of DNA damage that slows cancer growth. So it sure seems like you'd want both.
One researcher I spoke with (more specifically about ATR inhibitors, as they more directly target ATM) said that they also caused some DNA damage as well as impeding the DNA repair, so maybe there's something to that.
Another oncologist told me combining the drugs (cytotoxic plus an inhibitor) would be more than my system could handle, but I'm handling the traditional cytotoxic (GAC) so well I'd be happy to give it a try, and then back off if necessary.
I'm not sure about all the legalities. My understanding is if a drug is approved for some other condition, it can be prescribed off-label for your condition, even outside of a clinical trial. But if not approved yet for any disease, then it can _only_ be used in the context of a trial.
In your particular case, because it's part of a trial, it has to follow whatever the trial protocol is, which sounds like they're testing out a PARP inhibitor as maintenance therapy for patients who are off the traditional cytotoxics. Since it has shown promise in BRCA1/2 and PALB, maybe they want to get more detailed data of PARP inhibition of ATM than past studies have revealed.
FWIW, MD Anderson has done some studies combining ATR and PARP inhibitors simultaneously. About halfway down this page: https://www.mdanderson.org/newsroom/results-fgfr-inhibitors-parp-atr-inhibitor-combinations.h00-159617856.html
I hope you'll keep us posted regarding the other trial you're hoping to get into.
Thanks and best wishes!
Replies to "@pendesk8 , like you, I also don't understand why the PARP inhibitor is not given in..."
Connect
PARP’s are used as maintenance therapy after primary chemo has lowered the tumor burden. Chemo itself is sufficient in interrupting the DNA cycle and causing cells to go into irreversible apoptosis. Combination chemo like Folfirinox is interrupting the DNA cell cycle at more than one point making treatment efficient in those that it works in.
There are a number of side effects to PARP’s with suppression of the bone marrow with RBC precursor cells affected most. These are the cells that mature into RBC’s. Suppression leads to anemia that can become severe and result in chemo being suspended. PARP’s can also affect WBC’s and Platelets which would also cause a halt to standard of care chemo. WBC’s of the granulocyte lineage play an important role in protecting against bacterial infections. A drop in WBC’s can lead to sepsis and death. Platelets are responsible for coagulation. The liver makes a number of clotting factors and is already under stress having to metabolize chemotherapy agents. Adding a PARP inhibitor adds more strew to the functioning of the liver that is vital in metabolizing drugs, producing different enzymes and filtering toxins from the blood.
The most serious side effect that can be caused by PARP’s is Myelodysplasia Syndrome (MDS). It results in toxicity to precursor cells in the bone marrow of RBC’s, WBC’s and Platelets causing mutations that can become Acute Myelogenous Leukemia (AML) which is not curable and results in death.