Oxaliplatin: What are the effects of dropping it from FOLFIRINOX?

I gave wrong date for CA-19 starting to rise. It was October 2022, not 2023!! My bad.

Hello Wheatley,
Your question about the correlation between oxeplatin and chemo is one I’ve had myself. Guessing it’s one that kills the newly dividing cells and as we know it’s all newly dividing cells cancer and non cancerous which is why some get neuropathy. I’m just guessing because just like you I found my surgeon and oncologist to give very vague or “I don’t know” to many questions. During the last 3 sessions of chemo my neuropathy started to get worse but my Ct was clear (except for a soft tissue area around hepatic and celiac arteries which they insist is scar tissue which showed up on 3rd to 2nd to last chemo) and CA marker around 6) so they took out oxyplatin though I begged them to leave it in. My chemo ended at end of June this year. My ca19-9 is just starting to rise 23-29-72-47. I’ll be taking another marker tomorrow so I’ll see where at. Also, my Ct (except for area they think is scar tissue of hepatic and celiac arteries) and PET scan and ultrasound are clear. Nice not having any neuropathy though. It’s actually my primary that is ordering my markers tests since the nurse practitioner at oncologist office and my surgeon think I was over reacting since my marker is still low (32 or 39 is officially the upper limit of normal). I’m changing insurance now and goi g with a ppo instead of hmo just in case I need to go to a center of excellence next year. Just be your own assertive advocate is what it takes!

I can't speak to your specifics, but can describe my own situation. I am stage 4, with no node involvement but several small mets visible when I had a staging laparoscopy in early April. Because of the mets, I do not qualify for any type of radiation or surgery. So far, I've completed 14 chemo cycles. We have decided that I'll continue as long as I want or as long as I'm getting results; when results start to lag, I can switch regimens and, later, look for a trial if I want.

My first eight cycles were Folfirinox. The first was at 80 percent of typical dose (reduced because I'm over 70, and the oncologist pointed out that the full dose was tested on people much younger than me); all other doses have been at 60 percent of typical due to the rough reaction I had to the first cycle. Beginning with cycle 9, the oxaliplatin was dropped from my regimen. My oncologist said that he prefers discontinuing it before neuropathy gets so bad that it's permanent and crippling. Please note, and this is sort of a reply to another post on another thread, we are not really striving for a cure, given my age; we're working toward stable disease and length and quality of life. I'd take a cure! But no guarantee it'll happen.

Having described all that, I can tell you that my CA 19-9 has gone down steadily since it first was taken in mid-March. I started at 1736. The most recent CA 19-9 for which I have a result is 35. It was taken before chemo no. 13 on 11/14, so it represents four cycles minus oxali. So, in answer to your question, in my case dropping the oxaliplatin didn't cause an increase in CA 19-9. But I'm only one patient. Pancreatic cancer tends to respond to platinum-based drugs, and omitting it may be linked to the rise in your CA 19-9. Many factors can make it go up, but those of us with pancreatic cancer are sensitive to an increase because yes, it can indicate a recurrence. So I would ask my oncologist to pursue a cause for that increase, in case something has developed that needs to be treated. I hope you can find the cause!

My layperson's sense is that all four elements of FOLFIRINOX work in concert to stop the cancer cells from replicating, and to kill them, but fwiw here's what the NCI offers:
"Oxaliplatin is a type of chemotherapy drug called an alkylating agent. It contains the metal platinum. It damages the DNA of cells and stops it from being copied. This stops or slows the growth of cancer cells and other rapidly growing cells and causes them to die."
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Please note, tho, that the NCI's lay description of irinotecan's function is semi-similar -- hence my sense that these cancer drugs work in concert, with the same goal but with somewhat different methods of achieving that goal:
"Irinotecan hydrochloride is a type of chemotherapy drug called a topoisomerase I inhibitor. It causes breaks that cannot be repaired in the DNA of cells. This stops the growth of cancer cells and other rapidly dividing cells and causes them to die."
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https://www.cancer.gov/about-cancer/treatment/drugs/oxaliplatin
https://www.cancer.gov/about-cancer/treatment/drugs/irinotecanhydrochloride
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And here's what drugs.com offers:
"Oxaliplatin is a cytotoxic chemotherapy drug used to treat cancer. It is a type of platinum drug and an alkylating agent.
. . . . . . . Like other alkylating agents, oxaliplatin works by interfering with the development of DNA in a cell. It stops cells from growing and multiplying and kills them. This helps to treat cancer which is caused by cells rapidly growing and dividing out of control."
https://www.drugs.com/oxaliplatin.html
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Although CA19-9 can rise for reasons unrelated to pancreatic cancer, I too would be dismayed about a rise and would want my onc. to tell me exactly what he plans to do in order to (1) figure out why it has risen, and (2) treat me if the rise does indicate that the cancer has returned. So I perhaps *those* questions are higher on the list than "What does oxaliplatin contribute, and did its absence prompt the rise of CA19-9 for me?"

If you can't get a clear answer from your doctor in the short term, perhaps call pancan.org ASAP (877-272-6226 / Mon – Fri, 7 a.m. – 5 p.m. PST), where knowledgeable volunteers *might* have some data or articles that could help answer your questions. But please do press your onc. with regard to "What does this rise mean, and how are you going to treat it?"

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!

Hi,
Have you heard, in your experience, what other causes besides recurrence can drive up that CA19-9? Mine is slowing rising, but I do have occasional nausea now and am feeling very tired these days.

Thanks,
mnewland

From https://www.sciencedirect.com/topics/medicine-and-dentistry/ca-19-9-antigen#:~:text=Interference%20of%20heterophilic%20antibodies%20causing,of%20CA%2D19%2D9.

"Elevated CA-19-9 levels usually precede the radiographic appearance of recurrent disease, but confirmation of disease progression should be pursued with imaging studies and/or biopsy. CA-19-9 can be elevated in many types of gastrointestinal cancer, such as colorectal cancer, esophageal cancer, and hepatocellular carcinoma. Apart from cancer, elevated levels may also occur in pancreatitis, cirrhosis, and diseases of the bile ducts. It can be elevated in people with obstruction of the bile duct. In patients who lack the Lewis antigen (a blood type protein on red blood cells), which is about 10% of the Caucasian population, CA-19-9 is not expressed even in those with large tumors. This is due to deficiency of the fucosyltransferase enzyme that is needed to produce CA-19-9 as well as the Lewis antigen. The use of a combined index of serum CA-19-9 and CEA (CA-19-9+[CEA×40]) has also been proposed for screening of cholangiocarcinoma.

"Interference of heterophilic antibodies causing false positive CA-19-9 results has been documented, and usually treating the specimen with heterophilic antibody-blocking agents can eliminate such interference. Patients with acute or chronic pancreatitis may also have elevated levels of CA-19-9. In addition, pulmonary diseases may also elevate CA-19-9 levels. Liver cirrhosis, Crohn’s disease, and benign gastrointestinal diseases can also increase CA-19-9 levels."

I'm not a medical professional; I just googled for reasons why CA 19-9 could be elevated. There are a bunch. That's what makes CA 19-9 a tricky tool to use for definitive diagnosis. On the other hand, I've always heard that the CA results are more reliable to track disease/treatment progress once you have a firm diagnosis. That's why, if my CA 19-9 were starting to rise, I would be pestering my oncologist for more assessment to pin down why.

Hi markymark!
I missed what ATR inhibitors are. I'm still stage 2 as far as i know, but this could possibly be changing. I ask because I have some type of ATM mutation "of unknown significance" (or the translation might be that there just isn't enough scientific evidence right now to support that my mutation is directly related to pancreatic cancer (even though my dad had it, and his mother had breast cancer in her 40's). I'm feel I probably do have an ATM mutation, so I'm interested to know about ATR.

I'm curious to know about Oxaliplatin too. My husband had a distal pancreactomy and splenectomy in July and is doing adjuvant chemo for six months. His 6th treatment was today, and he had a reaction to the Oxaliplatin - red face and neck, nausea, tingling tongue, lips and hands, stinging lower back and legs, restless legs, high blood pressure, itchy hot hands and feet, tightness in jaw, abdominal pressure and light headedness. They stopped the infusion immediately and an entire team showed up with oxygen and intervention medicines (Benadryl, Pepcid).

The doctor said that this was a reaction to the Oxaliplatin, so they didn't continue with it. This is his second reaction to Oxaliplatin - the first time was after treatment #3, he had a fever which they said was from the Oxaliplatin after they ruled out every kind of virus and bacteria.

The nurse had said that since this is his second reaction, they might not want to continue with the Oxaliplatin. However, I just saw the notes in the portal which indicate that they want him to pre-medicate with steroids and Claritin before the next treatment.

Ironically, just before the treatment, I had asked about the efficacy of the chemo regimen if the Oxaliplatin was removed and the nurse practitioner said that it would be fine, they usually remove Oxaliplatin later in the regimen if neuropathy worsens. She said that they like to start with the 3 meds.

Today was very scary. I was really hoping that they'd remove the Oxaliplatin going forward.

Has anyone else had this experience? If so, were you successful with the pre-med steroids and Claritin? Thank you.

I confess I don't have the biochemistry background to comprehend it, much less explain it in plain English, so I'll just take a shot and recommend follow-up w/ someone competent.

ATM = ataxia-telangiectasia mutated
ATR = ataxia-telangiectasia and rad3-related

Both are proteins cancer cells call on to try and repair themselves when damage occurs to their DNA. ATR and ATM appear similar enough that one class of drugs (ATR Inhibitors) can work to prevent either mode of repair. Without repair, the cell will most likely die without reproducing.

There is a long list of ATRi drugs in the first column of Table 1 in this paper:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10323102/
The table also lists other drugs (including PARP inhibitors) that the ATRi is being combined with.

I must repeat that I only understand 1% of what I typed above and offer no guarantee of accuracy.