Has anyone had Folfirinox stop working and had to start a new chemo dr

I only got a so-so response to 6 months (12 rounds) of Folfirinox before Whipple. No new tumors or mets during the treatment, but the primary tumor (in pancreas head) barely changed size-wise. CA19-9 trended upward slightly from mid-100's to low 200's in that period.

Since my post-Whipple recurrence (original site plus mets), I've been on Gemcitabine + Abraxane + Cisplatin since late January (20 biweekly treatments so far).

My multiple tumors have still remained about the same size. Very minor shrinkage on a few, but no new mets. Big difference is CA19-9, which was 677 at the start of treatment, came down to normal (33) 3 weeks ago for one reading, but has been hovering in the low 40's for 2 months.

All-in-all, I've found the current regiment a good bit easier than Folfirinox. Some neuropathy, but less. A little less fatigue. Biggest difference is complete hair loss.

I'm not sure why one regimen works better than the other for different people. My only deviation from a statistically "typical" population is an ATM mutation. But I wish I had switched (or gone straight to surgery) three months into my Folfirinox rather than dragging it out for 3 more.

Biopsies are only needed for some trials, not all. Different studies specify what is necessary. It may be that some combination of imaging, CA19-9, and other bloodwork is enough. If you do have a biopsy done, ask them to take as much tissue as possible so there will be enough to share with other potential trial sites. If you're doing one of the trials where they train your own cells to recognize cancer and then reinject them to fight it, you probably will need a good amount of tissue biopsied to start with.

I spoke with the folks at https://storemytumor.com/ a couple weeks ago. They have a service where they will store as much tissue as you can send them. It's frozen slowly so that it can be revived into a "live" state for use later. Not cheap, but an option.

The last surgeon I spoke with said he'd want me off chemo for 4 weeks before removing any tumors via an open or laparoscopic biopsy, more to ensure proper healing than "cleanup" for a study. But there was one tumor near my belly button he could have sample percutaneously with an 18-gauge core biopsy need and local anesthetic, with no need to stop chemo.

If it's been a while since your original biopsy, another one might not hurt just in case the tumor has mutated since then. Maybe the percutaneous approach would work for you as a quick and affordable way to get it done before starting new chemo. Starting any new chemo will probably disqualify you from certain trials, but that's just a sad fact of life. I wouldn't delay resumption of systemic chemo too long, as the PC can spread really, really fast without it.

There are several trials going on involving CAR T-cells and Natural Killer cells that are open to people currently on chemo, as long as your blood/DNA have all the right flavors.

Thank you for all the info. MSK felt the new spot on my liver is too small to obtain enough tissue for a vaccine. I will be sure to ask about the biopsies for the trials tho. My original biopsy when I was diagnosed did not provide enough tissue for complete testing. So it was discouraging.
You seem to know a lot about the trials. Did u register with PanCan?

My local oncologist suggested starting me back on Folfirinox first since my tumor was stable even tho CA19s were creeping up. MSK suggested switching chemos. Both gave good reasoning for their suggestion so I’m not sure what I will ask for. I will be meeting with my local oncologist in a few days to discuss. I feel like I know what to expect with Folfirinox and kind of got into a rhythm with the treatments, but am worried it stopped working since the CA19s were rising. You said the Gemcitabine combination was administered biweekly. I’ve read that it can be also given once a week for 3 weeks (day 1,8,15) and off for week 4. Not sure why some teams administer it one way and others a different way.

Thanks for sharing your info.

@robee , You're very welcome, and... I might lean toward the opinion of MSK over a local oncologist, but with considerations:

1) Will you be getting the chemo at MSK regularly, or getting it locally? If local, make sure your local oncologist has a good communication channel open w/ your MSK "consulting" oncologist and is willing to collaborate with them on your treatment when appropriate.

2) Since you've already done Folfirinox, you know what it's like, you know its relative (in-)effectiveness, and your system is currently "clean," I would personally choose a different chemo regimen just to see what kind of response it produces. That would include very frequent CA19-9 monitoring, Signatera ctDNA tests if possible, and new scans 2 months out, absolute max no longer than 3, to assess. I'm not sure exactly which cocktail MSK was recommending, but Gem seems like the basis for most, and is affordable. They could couple it with cisplatin (especially if you have an appropriate mutation) and/or Abraxane. Abraxane is very expensive and not always covered by insurance (at least not w/o appeals and paperwork), so it might not be approved by the time you start. (Same thing happened with me.)

If you wanted to try a "somewhat scientifically controlled" experiment, you might increase by one drug at a time; e.g., do 3 treatments on Gem only, then 3 on Gem + Cis, then 3 on Gem + Cis + Abraxane, with CA19-9 testing accompanying every step. That would give your body time to adjust, save the worst effects (hair loss and neuropathy) until last, and allow all the Abraxane paperwork approvals to go through.

I must repeat the disclaimer here that I have no medical training, and that a lot of doctors are not receptive to stuff that requires extra work like that, but if you're a good advocate and basically volunteer yourself as a guinea pig that will do most of the work, maybe they'll be receptive. The biggest, most obvious downside and risk is that if you're not starting with the full dose of everything, there's a chance disease could spread while you're experimenting. But my take is that if they're recommending Folfirinox only and it's not the right med for YOU, disease could spread anyway; and, if the others are recommending ONLY Gem, then planning for immediate escalation with the other two drugs provides a stronger treatment option.

Now 9 months into my GCA regimen, with neuropathy and fatigue adding up, two oncologists have recommended I either reduce the Cis/Abrax doses or eliminate them completely and go with Gem only. But I'm against that so far; I'm not going to stop a treatment that seems to be working otherwise at controlling disease, and I'd rather have neuropathy than a spreading cancer. One onco has a possible trial I'll find out about next month, but until then, I'm going full steam ahead on the present course. I'll switch only if there's something more promising.

Regarding the cycles and schedule of Gem/Cis/Abrax, I don't know how biweekly or 3-on/1-off is chosen, or if it's very specific to my exact combo and dose. For me, biweekly works because of the travel involved. I did ask about a schedule of once every 3 weeks instead of every 2 weeks with a dose reduction, and the PA said the research they followed was based on 2-week intervals (tied to cell growth cycles and rates, etc), but it does seem like 3 weeks out of every 4 provides some extra cytotoxic power.

Finally, I wish I knew a lot more about trials than I do. 🙁 What I've learned, aside from reading, has mostly come from the trials I applied to but didn't qualify for or was accepted into but couldn't travel for.

As far as trials themselves go: Yes, I did register with PanCan.org, and they have provided me updated lists several times, although a bit too broad sometimes. I also registered with CancerCommons.org; they assigned a PhD researcher to my case and provided a short list of very detailed trial recommendations. It's a worthwhile option if you're comfortable providing them as much info as they ask for,

One extra postscript regarding trials:

What I've found about trials is that no matter who your oncology provider is, you probably won't hear from them about any trials other than the ones they're actively participating in, so you have to do a lot of research. E.g., if you're at MD Anderson, Mayo, Hopkins, Cleveland Clinic, Farber, Langone, MSK, etc, you'll probably only hear from them about studies they're engaged in. I've not heard of them sending patients somewhere else for a more appropriate trials, so a lot of that falls back onto the patient or advocate.

See comments above about PanCan.org and CancerCommons.org.

If you're searching the government website, it can be hard to filter out trials for the right disease. Now that "tumor agnostic" treatment is becoming a thing, where they treat you more by the mutation rather than the organ of origin, you may have to look a little deeper. E.g., one trial I'm applying for was created primarily for ovarian cancer patients with peritoneal mets, but they decided pancreatic cancer with peritoneal mets was a similar enough target they that opened it for that as well.

As such, using the right keywords in your search can be tricky. If you're looking for a specific drug, it might be listed only by its internal lab/developer name (ABC-123) instead of its generic name (yuckamibalab) or its trade name (Corrupto). If you're searching meds to treat a specific mutation (e.g., "ATM") you can search for that, but you might get too many or two few hits. Searching for the class of drugs relevant to that mutation (ATR Inhibitor, PARP Inhibitor, etc...) or characteristics of the mutation (DNA Damage Repair) might help, but it's REALLY time consuming, tiresome, and not very fruitful. That's where PanCan and CancerCommons can help.

When you find a trial on the government website, it usually lists a principal investigator by name; sometimes with email and phone contacts. That's one place where you can get more info. But if the "locations" tab lists other sites, it's worth contacting them directly if possible (by phone and email, in case your email gets ignored or filtered into their spam folder). The government website is often out of date wrt studies that are open/closed/recruiting etc, so get the info for each local site if you can and follow up directly.

robee - Beginning late May of this year, following diagnosis of adenocarcinoma at the head of my pancreas (Stage 1b), I began neo-adjuvant treatment with Folfirinox. That ended after 4 cycles due to anaphylactic reaction. I then began treatment with Gemcitabine and Abraxane (once a week for two weeks, then a week off). My highest CA19.9 level was 641 at the beginning of chemo in late May. Since that time my CA19.9 fell steadily to a low of 44 three weeks ago... though my last CA19.9 result of one week ago bumped up a bit to 55. Most recent CT Scans show about 15% tumor shrinkage. Today is my last full strength Gem/Abrax infusion before heading back to Mayo next week for a month of radiation therapy. (I understand I'll be given a reduced dose of IV Gemcitabine w/o Abraxane while receiving proton beam radiation treatments). The Gem/Abrax side effects has been the ongoing and worsening numbness to my feet, as well as persistent daily chills/body aches that begin nearly every afternoon once the effects of the IV steroid (Decadron) wear off two days after each infusion. These flu-like signs/symptoms dissipate gradually, so the last 3-4 days of my two week break of Gem/Abrax infusions side-effects usually are not very noticeable..... unlike the steadily worsening numbness to my feet. Hope this helps. Take care.

Great detail and information here. Thank you all! I would add only one post note.
It seems logical to change chemotherapy treatments before your body has built a complete resistance to one. I initially did Fulfurinox and had great results so why not do it again when my recurrence appeared? I certainly posed that question. They switched me to Gemzar and it has worked too. Keeping the big F in our back pocket I suppose.

Studies are pointing to the effectiveness of Gemzar every other week. I tried to do the 1,8,15 regimen but my platelets would not hold up.

Every other week strategy brought my numbers to normal and opened a window for surgery.

Lastly, my oncologist has mentioned a drug Omnivide. My post surgery visit is today. I am looking deeply for KRAS G12D trials but am anxious to hear their recommendations for next steps.

Enjoy these beautiful Fall days ya’ll. Vitamin D is good for all of us!

I hadn't heard of that medication, so I googled it. The brand name is Onivyde, and it's a form of irinotecan. It's used in patients whose cancer has spread and who have already had gemcitabine. Onivyde is dosed with 5FU (fluorouracil) and leucovorin. (I don't know how it's administered, but I'm guessing infusion. I assume the 5FU would be administered via the 46-hour take-home pump.) I'm no medical professional, but to me it sounds like a version of Folfirinox minus the oxaliplatin. So I'm curious what the advantage is versus the standard Folfiri (minus the oxali). I'm not a candidate for the drug yet, but I will make a note of it and ask my oncologist. I'm interested to hear what you learn as well. Thanks for mentioning it!

Diagnosed Nov 1 2022 with tumor in tail of pancreas and mets to liver and lung. CA19-9 was 1500

After several rounds of Folfirinox markers were down and tumors had shrunk by half and tumor in lung was gone.

25 rounds of Folfirinox tumors had shrunk more and markers were down to 15. I took a 3 month break from chemo. 4 more rounds of Folfirinox and Tumors came back, markers are up to 150. Doc says Folfirinox is no longer working. I asked if the tumor had evolved to be resitant to Folfirinox, Doc says not exactly but you could think of it that way. Just got my first round of Gemcitabine yesterday. I'm on the 3 weeks on 1 week off but Doc says some people drop back to the every other week plan.

Hi packrat256,
I was diagnosed with pancreatic cancer in September 2022 with it in the tail and metastasized to 1 lymph node. My dad had it back in 1999 and seeing how extremely aggressive it was I opted for surgery ASAP (we have the ATM gene). I had a fistula leak after surgery and had a longer break between post surgery and start of chemotherapy with 4-FU (fulfirnox) for 6 months; 12 rounds. I had questioned during early chemo (based on the CT readings showing a lit up area) if it was in my hepatic artery and my oncologist and young surgeon deferred to the interpretation of the radiologist who said it was scar tissue. I was really frustrated with that response because the comment said it had grown in size and I had read that the hepatic/celiac artery was one of the most common sites of reoccurrence.4.5 months after chemo ended it was diagnosed (via MRI and ERCPUS. To have spread to my liver and most likely in abdominal peritoneum. At that point I changed from Hoag Oncologist to UCLA (center of excellence). In January 2024 I started chemo again with GAC initially 3 weeks on as dr recognized it was aggressive. my antigen went from 23 in September 2023 to 3840 in early Jan 2024. My antigen is now at 24 and last week I began my treatments biweekly. My lesions in liver have shrunk and 1 no longer visible;however, the masses in abdominal peritoneum and hepatic artery remain unchanged in size or stable. Make sure your care is with a center of excellence and I wish you well!

I had 5FU plus irinotecan and oxiplatin though oxiplatin was eliminated after session 8 due to slight ongoing symptoms of neuropathy (which later disappeared). My antigen went down to 6 by the end of session 12. This treatment did not kill soft tissue around my hepatic/celiac artery and so 4.5 months after chemo ended my cancer was trying to come back full fledge. It spread to my liver and abdominal peritonuem. I’m now being treated with the GAC combo with the “C” being cisplatin. I’ve only had about 8 or 9 sessions and I’m feeling great with antigen gown to 24 and hoping/praying to go the distance! I wish you fantastic results!