Switch from Folfirinox to Gem/Abrax due to non response

I'll try to write up a longer reply this weekend, but sometimes one drug works better for some people than others.

In my case, 12 rounds of Folfirinox before surgery didn't do much other than stabilize things: Tumor stayed at Stage-2 throughout and I was able to get Whippled after 6 months. CA19-9 trended upward slowly on Folfirinox (mid-100's to mid-200's).

Tumor came back at original site (head of pancreas) 4.5 months after surgery, metastasized while we spent 7 weeks confirming it & planning treatment.

Started biweekly treatment on Gemcitabine + Abraxane + Cisplatin in January with CA19-9 at 677; it started a rapid decline soon after, and has been bouncing between mid-30's to mid-50's since September, and my MRI this week showed some tumor shrinkage. Plus it's an easier regimen than Folfirinox. (I've had 22 rounds of the GAC so far.)

I don't know why some people respond better than others to one regimen vs the other. It could be the mutation I have (ATM), or the fact that I'm blood type A+ or the fact that I eat BBQ and wash it down with dark chocolate. I just don't know. I don't see enough studies broken down to the fine levels of detail that identify the best drug for an individual patient in advance or before too long.

The platinum-based drugs are believed to benefit patients with the ATM mutation (and maybe some others), but Folfirinox has platinum (Oxaliplatin) which was part of the recipe that didn't do much for me. One oncologist I spoke with said cisplatin is "just the other one they use in the non-Folfirinox standard of care recipe" but that it might have a synergistic effect at penetrating the tumor's outer layers when combined with Abraxane. Maybe Oxaliplatin with Abraxane would do the same thing.

I'm glad you found out after 4 months rather than 6 that the Folfirinox wasn't doing enough, but really sorry you found out the way you did.

I wish you and your dad the best with this.

This is a bit odd. Were the first two locations reviewing the same scan(s) and then Mayo did their own scans for review?

It is truly unclear why a treatment works as it does on some but not others. I was stage IV. I did folfurinox and when they went in for pancreadectomy the tumor was dead. My CA19-9 went from 23k to around 35 at surgery. I also had liver tumors that were resected at found to be 95% necrotic. Fast forward, a small recurrence caught early and I am now on GEMZAR. It seems to be working. Last CA19-9 at 29. I have the KRAS G12-D mutation-most common of all and no immunotherapies yet!

I didn’t understand why all advised not to go back to folfurinox, but maybe it’s a back pocket tool for later.

Depending on staging and location, surgery can be curative. But I have learned the timing is very important along with the plan afterwards.

My hope for him is that the chemo can provide shrinkage to get you to the next modality.

kirdyk,

To the chronology ... you father's pan can was staged locally (what stage?), and the eight rounds of chemo by a local hospital, then assessed as suitable for surgery, then you visited Mayo Rochester and were told he was not?

My experience at Mayo Rochester is that they believe their equipment is better, their staff and doctors are better and their process is better. I found their portal for patients to be outstanding, allowing full access to all tests and assessments. Have you reviewed these findings? I know it is hard due to the complex terminology used.

My recommendation is to relocate to Mayo Rochester, and immediately restart whichever chemo regimen their oncologists recommend.

@kirdyk ,

Have they done any genetic testing on your dad (germline and somatic) to determine any hereditary or tumor-evolved mutations? Those may help guide the current treatment and could definitely play an important role in selecting (and being admitted to) future clinical trials. If not, ask the oncologist treating him now or the doc(s) you saw at Mayo to order those ASAP so you will have that data when the next level of decisions have to be made.

Regarding the ineffectiveness of Folfirinox: What does his CA19-9 trend look like from baseline to present? Has he been getting it tested biweekly, before every infusion? If not, it might be helpful to request it at least that often so you have more data to fill in the gaps, and will get a quicker look and more easily identifiable trendline if he switches to a different chemo regimen.

Is there any other data besides imaging and CA19-9 being used to evaluate his progress? I assume there was a biopsy (via EUS) at his initial diagnosis. It might be helpful if they did full NGS (next-generation sequencing) on the tissue extracted during that procedure. If they saved enough tissue to have Natera construct their "Signatera" test from it, you could monitor ctDNA (circulating tumor DNA) as another way to measure treatment response. If any viable tissue remains available, you should also ask the sharp minds at Mayo if they could perform sensitivity testing on that tissue in their lab, and determine if the switch to Gem + Abraxane +/- platinum shows promise there. Similarly, if he has an approved mutation like BRCA or PALB, they could treat with a PARP inhibitor instead of (probably not on top of) an existing standard-of-care treatment.

I have read that OXaliplatin (the fourth ingredient in FolfirinOX) can be more effective (with caveats) than Cisplatin, but the typical third ingredient in the Gemcitabine+Abraxane+platinum triplet is usually cisplatin rather than oxaliplatin. I don't know if that's an FDA requirement or just an habitual (and perhaps outdated) path, but I will be asking my oncologist about a potential switch for myself this week.

Two quotes I've read read from Dr. Google are pasted after the

--- DISCLAIMER --- I have not read these papers all the way through, only scanned and found these selected highlights. I have no medical training. The cited papers are written for gastric cancers in general, not pancreatic cancer in particular. I have not read enough related papers to determine whether the quotes pasted below are part of a more widely accepted consensus.
--- END DISCLAIMER ---

1) https://link.springer.com/article/10.1007/s10120-011-0007-7#:~:text=The%20in%20vitro%20activity%20of,result%20in%20a%20survival%20benefit.
"The in vitro activity of these two platinum compounds has been well investigated and it is known that oxaliplatin induces more double-strandbreaks in DNA adducts compared with cisplatin, with increased cytotoxicity [6]. This could translate into a better clinical activity and possibly result in a survival benefit. "

2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547983/#:~:text=In%20addition%2C%20oxaliplatin%2Dbased%20therapy,neutropenia%20than%20cisplatin%2Dbased%20regimen.
"Results: 2,140 patients from six phase II or III RCTs were included. Compared to cisplatin-based therapy, subjects who received oxaliplatin-based treatment had significantly higher PRR, ORR and DCR, but not CRR. In addition, oxaliplatin-based therapy significantly decreased all grades of leukopenia, neutropenia, anemia, febrile neutropenia, nausea, stomatitis, creatinine elevation and thromboembolism, as well as grades 3-4 of leukopenia, neutropenia, anemia and febrile neutropenia than cisplatin-based regimen. However, oxaliplatin-based treatment strikingly increased the risk of thrombocytopenia, sensory neuropathy, diarrhea, fatigue and liver dysfunction.
Conclusions: Oxaliplatin-based regimen is superior to cisplatin-based regimen in tumour remission as first-line chemotherapy for advanced GC, and is associated with less toxicity and better tolerability."

Regarding radiation: It depends on a lot of things. In my case, the tumors are too close to other damage-sensitive areas; and too spread out to hit with one beam or implanted radioactive "brachytherapy" seed. Those are both options you could ask about. Not every center has proton beam equipment, and those that don't won't always refer you to outside providers who do. There are also newer "one-directional" brachytherapy products like the CivaSheet that might be an option, but is also not widely used or referred. So do a little homework on those, and when you ask about the potential effectiveness, be prepared to evaluate the doctor's body language as well as wording, as they can sometimes be contradictory 🙁 I emailed Civa to ask for a list of doctors/institutions using their products, but they never answered. Their website only had a video testimonial referencing on in Virginia. There might be more on YouTube.

Regarding surgery: Some surgeons are much more conservative than others, more experienced than others, and more willing to do surgery first w/o neoadjuvant chemo than others. Except for the surgeons who do HIPEC (a rather rare and radical procedure), most won't operate if there's evidence of distant or widespread metastasis. I don't know if they consider lymph nodes along the aorta are considered regional, locally advanced, or distant-metastatic, but if Mayo is calling him stage-4, it sounds like metastatic. On the other hand, if Mayo declared him inoperable because of complexity rather than widespread metastasis, you could seek alternate surgical opinions. Maybe just get another surgeon to review his most recent imaging remotely. Dr. Christopher Wolfgang at NY Langone (previously Johns Hopkins) is widely regarded as someone competent and willing to take on some very difficult cases. Could be worth a call.

There is also a surgical technique called "IRE" (Irreversible Electroporation) that uses an electric field to kill tumor cells. Not widely used, but the company's website did have a list of providers. It can be used on the pancreas, but I doubt it could be used around the aorta. That's such a sensitive and critical area that you can't afford to let anyone just poke around. I really have no experience or insight into this beyond the awareness of those products listed above. Most surgeons take their "do no harm" oath (and their potential to be sued) very seriously, and they understand the difficulty or impossibility of recovering from radical surgeries that are pointless in the long term, and tend to avoid them. Another issue is that surgeons typically require a 1-month washout before surgery and 1-2 months healing time afterward, so that could be a 3-month period with no systemic chemo to treat any other mets (micro or macro), allowing cancer to spread elsewhere.

Continued reply; forum apparently wants smaller pieces...

Regarding clinical trials: It can be a frustrating experience simply finding a good one, much less actually getting into one. Most treating institutions I've dealt with don't offer up awareness of what's going on at other institutions, so you'll only hear about the ones they are participating in. That leaves the patient to do a whole lot of homework. The US government websites (NCT, NIH, cancer.gov) are somewhat comprehensive, but sometimes data overload. Pancan.org and CancerCommons.org can be very helpful in narrowing the focus down to realistic and appropriate trials. Also, the biggest and most respected institutions have lots of trials going on, and their web pages might be more up to date than the government's. That can also help the focus if you're tied to one specific region.

Also, you might find relevant trials that are not specific to pancreatic cancer, so don't let the study headline/title discourage you or dissuade you from looking deeper. A lot of the modern treatments are considered "tumor agnostic" meaning it doesn't really matter where the tumor originated as much as its genetic makeup, similarity of tumor microenvironment, etc... I'm in the "possible candidate pipeline" for study originally created to treat ovarian cancer that has metastasized into the peritoneum, since my pancreas solid tumors are solid and have also metastasized there.

Overall, if your dad is handling Folfirinox well, it sounds like he's in pretty good general health, able to tolerate other strong/aggressive treatments, and is also fortunate to have you as his advocate. You will have a lot of on your plate both caring for him and navigating the path forward. I wish you both all the best, and hope you can share whatever you learn here on the forums.

Hi @kirdyq, you may also be interested in these related discussions:
- Anyone on Gemcitabine with Abraxane? How long? Effective?
https://connect.mayoclinic.org/discussion/gemcitabine-and-abraxane/
- Changing chemo regimen after 4 cycles of Folfirinox?
https://connect.mayoclinic.org/discussion/changing-chemo-regimen-after-4-cycles-of-folfirinox/

Any update?