Oxaliplatin & Nab-paclitaxel Neuropathy - Longer Infusion Time?

Posted by hopefaithcourage @hopefaithcourage, May 21 7:15pm

My dad was diagnosed with pancreatic cancer in late January 2023 with encasement of PV/SMV and abutment/180degree encasement of SMA (he was deemed to be borderline resectable). He went through 10 rounds (5 cycles) of FOLFIRINOX (stable to slight progression of disease on CT, no significant decrease in CA 19-9), then 8 treatments of Gemzar/Abraxane (3 cycles) before getting chemoradiation and then surgery in mid-December 2023 (total pancreatectomy). There was some peripheral neuropathy while he was on FOLFIRINOX, but this was accelerated by the time he switched over to and finished GemAb (coasting effect?). As of today, the neuropathy in his hands has nearly resolved, but it is still quite strong in his feet.

Because the latest CT scan (early May 2024) indicates peritoneal carcinomatosis, increasing nodularity in his left adrenal gland, and soft tissue encasement of common hepatic and left gastric arteries, he has to be back on chemotherapy while we search for an appropriate trial. He had his first infusion of Gemzar (80% dose) / Abraxane(50% dose) last week, but he's already telling me that the tingling sensation has started to come back in his hands (his feet are still affected by neuropathy from the chemotherapy prior to surgery).

Others on this board have mentioned cold therapy and compression socks/gloves as potential mitigators to chemo induced peripheral neuropathy. While I searched for other workarounds, I found that dose reduction (which he's already on 50% Abraxane) and longer infusion time may also help minimize the neuropathy effect. I understand some of our forum members are affected by this as well after having been on the cocktail for sometime (@markymarkfl, @mnewland99), so am wondering if anyone has requested the "longer infusion time" approach with their oncologists? I'm thinking about asking this for my dad when he has infusion next week.

Scientific work that discusses the benefit of extending Abraxane (nab-paclitaxel) infusion time from 30 minutes to 2 hours to help with neuropathy. The paper discusses results for lung cancer, but I believe it may also be applicable to pancreatic cancer as well? I cannot post link, but the title of the paper is "A Phase 2 Study of Weekly Albumin-Bound Paclitaxel (Abraxane®) Given as a Two-Hour Infusion". You can do a search on Google.

A similar trial is looking at the same effect for oxaliplatin (being conducted here at Emory in our home state GA). If one has time to spare (from 2- to 6-hour infusion) then this may be worth it? I couldn't find any results for this yet, though. The trial is "2 Versus 6 Hour Oxaliplatin Infusions in Patients With Gastrointestinal Cancers".

Interested in more discussions like this? Go to the Pancreatic Cancer Support Group.

Disclaimer: I have ZERO medical training. These are just rambling thoughts and hypotheses based on one patient's experience and a few papers/posts I've read.

Oxaliplatin and Abraxane are both notorious for causing CIPN, so it's hard to say whether the neuropathy is from Oxaliplatin coasting or Abraxane startup. My coasting (increase) and resolution of neuropathy from 6 months of Folfirinox was about 7 months. After 15 months on Gemcitabine + Abraxane + Cisplatin, I'm now off chemo for 6 weeks, and the neuropathy is still present in my hands and feet.

The study at Emory https://www.clinicaltrials.gov/study/NCT03800693 still appears to be recruiting participants, but indicates it has been open since 2019. With that much history, I would ask your oncologist to contact the study coordinator directly to see how much data they have on effectiveness with previous patients.

Although I found the Emory trial link above, it didn't have results attached and I couldn't find the paper you mentioned reporting outcomes for lung cancer patients.

That study is a brilliant, out-of-the-box idea. My layman's analogy for how it might work is the potential hearing (ear nerve) damage from one loud shotgun blast versus a longer but quieter stream of machine gun fire. If the nerve sensitivity to "volume" (chemo concentration at any one instant) outweighs the sensitivity to duration for an equivalent dose, then the longer infusion time might very well reduce the nerve damage.

You're already well into experimental territory here, so some things you might consider as you make a guinea pig of yourself:

1) Icing and compression both have some data suggesting they help reduce CIPN; there seems to be more data supporting icing than compression, but it may just be for lack of study. Icing in general is not very comfortable, so if you're trying to combine methods to reduce neuropathy by icing during a longer infusion time, it will be uncomfortable for that longer period of time and thus might not be practical.

2) Icing _might_ be contraindicated with Folfirinox due to the increased cold sensitivity caused by Oxaliplatin. That is a distinctly different sensation than the general numbness and tingling or pin-pricks of CIPN, and I never experienced the cold sensitivity with Abraxane. Two patients on the forum here have stated their oncologist recommended against icing with Oxaliplatin. My layman's analogy behind that rationale is that it would be like staring at the sun after your eyes have spent weeks acclimating to a dark cave -- a sudden, total nerve overload.

3) Compression is a lot easier to tolerate than icing, but an effective amount of compression on the feet is hard to determine. The only study data I read for compression only applied to hands/fingertips. The patients wore two surgical gloves (both a size to small) overlapped on the same hand to achieve the compression. This left the other hand untreated as a control for the experiment. I tried it a few times with gloves on both hands, since I wanted to protect both hands and not come out lopsided. It was a lot more tolerable than icing and easier to browse the web on my phone while killing time.

4) The hypothesis behind icing and compression is that by constricting blood vessels in the hands and feet, the reduced blood flow reduces the chemo exposure to those nerves. Therapies I've read about only applied the ice or compression while the chemo was being infused, which is typically in the 30-90 minute range. The concentrations would obviously be highest during that period, but I would suspect they remain at nerve-damaging levels for several hours. For that reason, continuing the icing/compression for "a while" after treatment may be beneficial and may also support the hypothesis that the nerves are exponentially less susceptible to damage at lower concentrations.

5) You might have to take dose-concentration effectiveness into account as a priority over neuropathy. If a "high-concentration assault" of Abraxane on tumor cells is more effective at killing them or keeping them in a senescent state than a lower concentration for longer time, I would personally lean toward killing the cancer cells. Another layman's hypothesis is that a lower concentration of the chemo might actually help cancer cells gradually adapt and develop resistance to the chemo. The old adage "Whatever doesn't kill you makes you stronger" may apply. My CA19-9 jumped after two treatments with a 15% reduction in Abraxane, so I recommend caution. But that was a reduction in total dose, which doesn't necessarily imply the original dose over a longer duration would have caused the same response.

6) One of my oncologists said acupuncture may help with neuropathy, and that his institution actually has a provider who will administer it. I've been skeptical of just walking into a random acupuncture clinic and asking for treatment of symptoms caused by a cancer treatment, but if your providers have an integrative medicine department or can refer you to one with professionals trained in a specific, appropriate modality of acupuncture, I'd say give it a try.

7) I've read that B vitamins can help with CIPN, but also make it worse if overdosed, so do your research and consult a professional before going beyond 100% of the RDA for any supplement. (In fact, check with your chemo provider's pharmacy specialist regarding compatibility of ANY supplement taken with your chemo.)

8) I occasionally see advertisements for stem cell treatments for neuropathy aimed mainly at diabetic patients. I have no idea if this is snake-oil quackery or a valid treatment, but if you have time to do some research, you might find something helpful for CIPN patients (keeping in mind that many of us PanCan patients are also diabetic).

At this point I have to reiterate the disclaimer that I have zero medical training, and that the content above is only for exploratory thought purposes. Discuss everything with a medical professional before taking action, but if you learn anything as a result, please share it here!

Wishing you the best, with sincere thanks for your original post exposing us to this novel idea.

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Slower infusion of a platin or taxane may lessen the chemo induced peripheral neuropathy (CIPN) but won’t eliminate it as the agent being used is still reaching peripheral nerves. Using cold therapy constricts the capillaries in the fingers and feet while cold is applied. After infusion is finished, the agent that is neurotoxic is now dilated in the circulation and not as toxic to peripheral nerves when the extremities warm up.

With onset of CIPN, using cold therapy may be intolerable to try at this point. Compression socks and gloves is the other alternative. There is a study that has been underway at Columbia Presbyterian Medical Center in NYC with three cohorts-the control group of no treatment, a cold therapy cohort and a compression therapy cohort. I don’t know if preliminary results have been released. I will be attending the American Society of Clinical Oncology meeting in Chicago beginning Friday and will be on the lookout for any abstract presentations or talks on prevention of CIPN and post effects treatment.

Regarding resolution of CIPN, I did 24 cycles of Folfirinox-significant more than standard of care. My fingers resolved in 12 months, cold sensitivity in 36 months and in the feet after 7.5 years. I never lost feeling in my feet-just decreased sensitivity from the balls of the feet to the toes. Because I was going to have more aggressive treatment with Folfirinox, my oncologist did alternate treatments in groups of six starting with Folfirinox and then resting cycles of 5-FU/Leucovorn for the next six. This alternating treatment resulted in less impact on peripheral nerves yet was efficacious and I had a robust response. It took care of going from a diagnosis of stage IV to NED after the 46th cycle. My neuropathy has completely resolved.

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@hopefaithcourage, I hope you saw the detailed and helpful replies from @stageivsurvivor and @markymarkfl. Have you and your father discussed reducing dosages and/or increasing the infusion time with his oncology team?

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@hopefaithcourage - Though less detailed and more basic than earlier replies, here is a source of fundamental information regarding CIPN.
https://www.mskcc.org/news/answers-faq-about-chemotherapy-induced-peripheral-neuropathy-cipn
https://www.mskcc.org/cancer-care/patient-education/managing-peripheral-neuropathy
Also this: https://www.foundationforpn.org/

For what it's worth, I was diagnosed 13 months ago with pancreatic cancer. I've have three short runs of chemo (Folfirinox, Gem/Abraxane, and Folfiri) that have resulted in moderate to severe peripheral neuropathy. The palms of my feet have been numb/tingly since my initial Folfirinox chemo that began 11 months ago. I've also had some, but less severe, sensory loss to my hands and fingers. Also a bit of occasional impaired body balance.

Best wishes to your dad, your family, and you.

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I've heard from more sources in the past two weeks that acupuncture can _sometimes_ be helpful with CIPN. Both Mayo Clinic and MD Anderson offer it through their Integrative Medicine programs, but apparently you have to ask your primary oncologist to submit a referral for it. I'm hoping to get in line for it soon. 🙂

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