DISCLAIMER: I HAVE NO MEDICAL TRAINING!

@wheatley , do you have any known, targetable mutations?

There are 3 traditional platinum drugs, in increasing order of side effects: carboplatin, cisplatin, and oxaliplatin.

Oxaliplatin is the "ox" in Folfirinox, which is the typical standard of care for people who are able to tolerate it (usually younger patients).

Cisplatin is the one typically added to Gemcitabine/Abraxane regimens.

Platinum agents are "said" (urban legend?) to be especially helpful in patients with mutations (BRCA1, BRCA2, PALB, ATM) that already have impaired DNA Damage Repair mechanisms. But some cancers (including PDAC) eventually become platinum resistant. It has been discovered (and approved) that PARP inhibitors are effective for people with BRCA1, BRCA2, PALB mutations (FDA jury still out on ATM) is they have responded well to platinum agents in the past. It also appears that if you were responding well to platinum but then waited until platinum resistance developed, you may have waited too long for PARP inhibitors to work their magic.

(ATR inhibitors likely work better on ATM mutations, but only in trials. You can't get them off-label afaik if they're not approved yet for some other cancer.)

Anyway, you could ask your oncologist if it's possible to add cisplatin or carboplatin instead of oxaliplatin to your Folfiri. I don't know if many are willing to do the homework for that, because it's "non-traditional," but that would at least get a platinum-based drug into your system.

You could also ask about switching to Gemcitabine+Abraxane with one of the platinums. I'm on that with cisplatin added. Neither of my med oncs would switch it out for oxaliplatin, and I didn't understand their explanation due to bad video connections. Nonetheless, I (with ATM mutation) have responded way better to the GAC triplet than I did to Folfirinox. You might just be developing resistance to Folfiri in general, or really need _some_ kind of platinum, or you might just be one of those people (like me) for whom the GA(+/-platinum) works better than Folfirinox. GAC has also been much easier to tolerate than Folfirinox.

As @jk77 pointed out, there is probably some kind of synergy between all the drugs in Folfirinox. In my GAC, my understanding (which could very well be wrong) is that the Abraxane has some anti-cancer properties of its own, but also helps the other drugs penetrate the outer "stroma" of PDAC cells.

Anyway, long story short:

Ask your onco about:

1) adding any of the platinums (a more tolerable one like cis or carbo) to your Folfiri if appropriate

2) switching to GemAbrax (with or without cis or carbo since they don't want to give you Oxali, and Abraxane already causes enough neuropathy on its own)

3) switching to a trial drug appropriate for any mutations you have

Wishing you the best, and hoping you'll share anything you learn with us!