How many FOLFIRINOX cycles are enough?

Congrats on the negative results!

Did you have any chemo (Folfirinox or otherwise) before the surgery?

I think 12 Folfirinox infusions is generally considered a "full course" regardless of whether they all occur before surgery, after surgery, or some mix of before and after.

The important thing would be how you're doing at the follow-up visits. If 12 biweekly Folfirinox treatments spans ~6 months, I assume you'd be getting CT/MRI at the 3-month and 6-month marks. Hopefully these are all clear.

It would benefit you greatly if your surgeon/pathology department could submit tumor tissue from your resection to Natera and have the Signatera blood test built for you from it to detect microscopic residual disease that imaging may miss. If anything is detected, a series of Signatera tests provides a numerical result that would tell you if the chemo is working or not.

I would also HIGHLY recommend regular CA19-9 testing now and over the next 6 months. Bi-weekly with your pre-Folfirinox bloodwork if possible would be ideal. Rising CA19-9 was indicative or my recurrence before it was caught by ctDNA tests or the 3-month post-op MRI.

The standard of care for PDAC and PACC forms of pancreatic cancer is 12 cycles of (m)Folfirinox when used for curative intent. That number was selected by a working committee of oncologists convened by either the National Clinical Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO) in response to the question as to how much of it was felt adequate to achieve no evidence of disease (N.E.D) while also being tolerable by the average patient receiving it.

The definition of N.E.D. no observable or detectable disease using current imaging techniques such as CT, MRI or PET. at the time treatment is completed. What is important to realize is that each of those imaging systems has a limit as to its lower threshold of sensitivity in detecting a cluster of cancer cells. What can not be detected should it be present after treatment finishes is termed Minimal Residual Disease (M.R.D.). It is the hope of the oncologist that this low level of potentially remaining disease is kept in check by one’s immune system. If the immune system gets challenged and weakens, M.R.D. Can become active and come back more aggressively. If resistance to the initial treatment did not occur, the same regimen can be tried again.

The statistics show that there is recidivism at a rate as high as 80% within 24 months of surgery and treatment. This is due to M.R.D. where remaining cells had become quiescent/dormant and not killed. Chemo works on actively growing/dividing cells but not cells that became quiescent and stayed in a G0 (zero) phase of the DNA cycle. This is why so many patients have recurrence of their cancer. There are no studies showing doing more cycles of the initial treatment improves the prognosis, so the risks of permanent neuropathy and other sequela related to the cytotoxic chemotherapy drugs outweigh the risk.

There are cases of patients who were stage IV doing well beyond 12 cycles that became long-term survivors. I did 24 cycles of Folfirinox of the original formulation that was 20% higher than what is used today. I have the germline BRCA2 mutation and entered a maintenance monotherapy trial of a PARP inhibitor medication after completing the 46th chemo cycle which was a resting cycle of 5-FU/Leucovorin. These were used as part of alternating groups of six between groups of six of Folfirinox to lessen the chance of developing permanent chemo induced peripheral neuropathy (CIPN. This alternate method of dosing was successful in preventing CIPN. I will reach 13 years survival, declared cured and one that is considered an “exceptional responder” being studied by a research lab at the NCI as to what factors contributed to achieving cure. Despite being a long-term survivor and declared cured, I remain vigilant and continue having an MRI/MRCP every 6 months as having a (g)BRCA2 mutation slightly increases my risk of developing a new primary pancreatic cancer as well as prostate and male breast cancer.

Another patient also stage IV did 37 cycles of the same formulation but the concentration was gradually decreased during treatment and has permanent neuropathy in her feet. A third patient I speak to frequently did 9 cycles and was then moved into a PARP inhibitor trial targeting her somatic BRCA mutation. She has surpassed 7 years and is N.E.D.

@pcand52, how are you doing on the FOLFIRINOX chemo regimen? What cycle are you currently on?

@stageivsurvivor, when you go for your MRI/MRCP scan every 6 months do they use contrast every time?

I've had 3 MRCP's with contrast every year since 2022 and have another MRCP that's due this June and keep hearing that the contrast can leave long lasting deposits in the brain and am a little concerned regarding this.

Hi
sorry for the delay
i was to have my 10th cycle monday but was posponed due to low level of neutrophils(white cells)
i had 7 cycles every 2 weeks and decided to have the treatment every 3 weeks instead with a
20 % dose reduction
the worse side effects were neuropathy in the hands and diarrhea
i will probably take the 10th but will probably stop as i cannot see why 12 treatments will be better than 10, especially if it really is "adjuvant"
I could tolerate 2 more but i am afraid of lasting sequels of the poison.
After 10 days of each treatment i can play tennis at a high level and also walk &skate 5 km +
I was very fit before starting the treatment and do not have any sequel from the last july surgery
So i am wondering if i am doing the right thing
the oncologists and internists i put the question to
all answered it was a good question......

The FDA is aware of Gadolinium that can remain in the system and has a committee in place for the monitoring of data from manufacturers, patients and medical facilities. To date there are no issues for individuals with normal kidney function. In Low-Risk Patients (Normal Kidney Function), the FDA considers gadolinium-based contrast agents generally safe, but they are monitoring for potential long-term effects.

In Higher-Risk Patients (Kidney Disease, Pregnant, Children, Frequent Scans): The FDA advises caution and use of macrocyclic GBCAs, which are less likely to release free gadolinium. If you are scheduled for an MRI, have the ordering physician specify on the procedure order to use GBCA’s.

Procedures have benefits and risks and a patient has to weight having a diagnostic procedure where there are no reports of serious sequela in those with normal kidney function to not having the procedure, missing development of a new primary tumor, metastatic disease or detection of a mucinous cyst with concerning features-thus missing the opportunity for earlier detection and savings one life.

I went through the challenges of the Whipple procedure, nearly losing my life to metastatic disease in my liver, going through 2 years of aggressive full-dose Folfirinox to save my life and achieve cure. The statistics speak for themselves in how recalcitrant pancreatic cancer is-it I has the worst record and 80% develop recurrence/progression within 24 months of treatment ending. The statistics of a new primary tumor occurring in the long-term survivor cohort is 15-20% in those that achieve 5 years and beyond. I’ve weighed the risks and I know what it is like doing the most potent chemotherapy to knock out advanced metastatic disease when it went undetected for months and the first chemo regimen had absolutely no effect. I accept the risk of no reports of anyone with healthy kidney function being impacted by life-threatening sequela using Gadolinium in the many years it has been in use for better detection of disease that results in treatment starting sooner when disease is easier to treat. Cumulative radiation from a CT and known issues with iodine-based contrast agents being harsh on the kidneys is why I chose to make the switch to MRI/MRCP for long-term surveillance.

Thanks for your in-depth reply @stageivsurvivor.

I have 2 IPMN's that have grown each year since the initial MRCP scan in 2022 and I'm due for another MRCP scan this June.

What does the GBCA's mean in macrocyclic GBCAs contrast?