Clinical trial (third line treatment) lurbinectedin and irinotecan

I advocated for aggressive chemotherapy of Folfirinox. This was the formulation used from 2011-2018…not the (m)Folfirinox used since 2018. The original version was 20% higher concentration. I had chemo every 15 days for 24 months without pause.

Because of the concern for permanent neuropathy, my oncologist did an alternate mode of administration. The first six cycles were Folfirinox. Cycles 7-12 removed the Irinotecan and Oxaliplatin. These were considered resting cycles to let my body recover, hopefully lessen the effects of neuropathy and not becoming permanent while keeping the tumors stable or just growing slowly until cycles 13-18 when all components were then given. This alternating dosing went until cycle 46 when a CT scan showed no more shrinkage. At this point, the six major tumors had shrunk approximately 75-80% and the smaller ones were no longer seen. It was likely what remained was scar tissue that eventually was cleared by immune system cells. After a two week  “wash-out period” of the 5-FU/Leucovorin, I entered a clinical trial testing a PARP inhibitor that targeted my gene mutation. At the point I entered the trial, I was likely already NED and probably any minimal residual disease was eliminated from the excessive chemo I had. So it was more likely the chemo is what did it and the clinical trial drug kept any new primary tumor from occurring.

I was 55 and in otherwise excellent physical condition from long-distance bike riding. My objective despite being stage IV was to attempt cure although I’m sure my team was thinking it was not likely to happen. My top priority was survival and as long as possible. It was all or nothing. I had no intention of stopping and was committed to sticking to my goal till the very end. This is why I advocated for the more aggressive approach and thankfully my team agreed to do it.

Was it doing excessive chemo, the clinical trial, a combination of the two or was there something unique about my immune system that made me what the NCI categorizes as an “exceptional responder” is not known. In those that are classified as exceptional responders, it is often observed that T-lymphocytes of a specific type can get past the fibroblast-stromal layer and penetrate deep into the tumors and work in conjunction with chemo. When I was asked if I was willing to submit to a biopsy of one of the liver mets after having such a robust response, I gave consent. There was one major problem- a review of my scans showed nothing remained to be biopsied. So what factors led to my becoming cured of stage IV remain a mystery.

From anecdotal observation of other long-term survivors that did aggressive Folfirinox or Gemzar/Abraxane, our diagnosis was made between the ages of 39-55. Most of us did significant bike riding or were runners. None of us ever smoked, did not or rarely drank, ate healthy with average BMI values and had no co-morbidities of any significance. We tolerated the chemo well and the major complaint was neuropathy.

I did develop neuropathy in the hands, fingers, balls of the feet to the toes. Sensitivity was dulled but I never lost feeling in the extremities. I always was ambulatory but did experience a loss of spatial awareness at times of where my feet were and occasionally caught the tips of my shoes when walking. I also noticed times where I was unable to walk in a straight line and tended to drift to the right. My hands and fingers cleared first followed by decreased sensitivity to cold which then resolved. That was close to one year. The feet took considerably longer. There was no improvement until 2.5 years after finishing chemo. The feet eventually resolved after 7.5 years.

Thank you for sharing! Sometimes we are our best advocates! I have always questioned my father's team about Folfirinox, and they've not been on board with it. He started on gem-abrax and then went to mFolfox, now Folfiri. I had always thought Folfirinox was the more aggressive regimen. Did you have a surgical resection at any point? Apologies if I've misunderstood your journey.

I advocated for aggressive chemotherapy of Folfirinox. This was the formulation used from 2011-2018…not the (m)Folfirinox used since 2018. The original version was 20% higher concentration. I had chemo every 15 days for 24 months without pause.

Because of the concern for permanent neuropathy, my oncologist did an alternate mode of administration. The first six cycles were Folfirinox. Cycles 7-12 removed the Irinotecan and Oxaliplatin. These were considered resting cycles to let my body recover, hopefully lessen the effects of neuropathy and not becoming permanent while keeping the tumors stable or just growing slowly until cycles 13-18 when all components were then given. This alternating dosing went until cycle 46 when a CT scan showed no more shrinkage. At this point, the six major tumors had shrunk approximately 75-80% and the smaller ones were no longer seen. It was likely what remained was scar tissue that eventually was cleared by immune system cells. After a two week  “wash-out period” of the 5-FU/Leucovorin, I entered a clinical trial testing a PARP inhibitor that targeted my gene mutation. At the point I entered the trial, I was likely already NED and probably any minimal residual disease was eliminated from the excessive chemo I had. So it was more likely the chemo is what did it and the clinical trial drug kept any new primary tumor from occurring.

I was 55 and in otherwise excellent physical condition from long-distance bike riding. My objective despite being stage IV was to attempt cure although I’m sure my team was thinking it was not likely to happen. My top priority was survival and as long as possible. It was all or nothing. I had no intention of stopping and was committed to sticking to my goal till the very end. This is why I advocated for the more aggressive approach and thankfully my team agreed to do it.

Was it doing excessive chemo, the clinical trial, a combination of the two or was there something unique about my immune system that made me what the NCI categorizes as an “exceptional responder” is not known. In those that are classified as exceptional responders, it is often observed that T-lymphocytes of a specific type can get past the fibroblast-stromal layer and penetrate deep into the tumors and work in conjunction with chemo. When I was asked if I was willing to submit to a biopsy of one of the liver mets after having such a robust response, I gave consent. There was one major problem- a review of my scans showed nothing remained to be biopsied. So what factors led to my becoming cured of stage IV remain a mystery.

From anecdotal observation of other long-term survivors that did aggressive Folfirinox or Gemzar/Abraxane, our diagnosis was made between the ages of 39-55. Most of us did significant bike riding or were runners. None of us ever smoked, did not or rarely drank, ate healthy with average BMI values and had no co-morbidities of any significance. We tolerated the chemo well and the major complaint was neuropathy.

I did develop neuropathy in the hands, fingers, balls of the feet to the toes. Sensitivity was dulled but I never lost feeling in the extremities. I always was ambulatory but did experience a loss of spatial awareness at times of where my feet were and occasionally caught the tips of my shoes when walking. I also noticed times where I was unable to walk in a straight line and tended to drift to the right. My hands and fingers cleared first followed by decreased sensitivity to cold which then resolved. That was close to one year. The feet took considerably longer. There was no improvement until 2.5 years after finishing chemo. The feet eventually resolved after 7.5 years.

A have a basic familiarity with a new trial testing lurbenectedin heading by Dr. Erkut Borazanci of HonorHealth as in its mode of action but not much more because of the clinical study just getting started. I do have experience with clinical trials so I can comment regarding my experience.

When I was facing a diagnosis of stage IV disease in 2012, even before starting standard of care treatment, I began looking at clinical trials. It is said that those with later stage pancreatic cancer participating in clinical trials may have better outcomes than standard of care. Every drug used in cancer treatment began as a clinical trial and had to show efficacy that was equal to or better in some way if it was being tested against an existing drug. My search became easier when testing revealed a genetic mutation that was targetable. It took 14 months until I found the trial that was a best match to my set of criteria matching the trial’s eligibility criteria.

For those not having genetic mutations or actionable biomarkers, a third type of clinical trial tests small molecule drugs. This is a very active area of clinical research and from understanding the mechanisms of how a drug works at the molecular level, drugs that were developed for other types of cancers or conditions offer the potential to treat other types of cancers. The clinical study I was in first was for a drug first tested on ovarian cancer and got approval. Then it was tested on breast cancer and approved for that use. Next was pancreatic and now it is being used for prostate as an example of how a drug’s application of use can evolve. It doesn’t work for every patient but for some, it has made the difference.

With clinical trials, a study participant is observed much more closely by the study team than someone doing standard of care. When I entered my trial, searching for treatments did not stop. I continued looking for other options should the trial not work. I wanted to be prepared and with limited targeted therapies, focused on small molecule drug trials. Fortunately the drug I obtained as targeted therapy with the objective of long-term maintenance monotherapy continues to work and I remain on the drug which continues to be provided free of charge for over 8.5 years now. I continue to be closely and frequently monitored for the drug which is well tolerated.

I advocated for aggressive chemotherapy of Folfirinox. This was the formulation used from 2011-2018…not the (m)Folfirinox used since 2018. The original version was 20% higher concentration. I had chemo every 15 days for 24 months without pause.

Because of the concern for permanent neuropathy, my oncologist did an alternate mode of administration. The first six cycles were Folfirinox. Cycles 7-12 removed the Irinotecan and Oxaliplatin. These were considered resting cycles to let my body recover, hopefully lessen the effects of neuropathy and not becoming permanent while keeping the tumors stable or just growing slowly until cycles 13-18 when all components were then given. This alternating dosing went until cycle 46 when a CT scan showed no more shrinkage. At this point, the six major tumors had shrunk approximately 75-80% and the smaller ones were no longer seen. It was likely what remained was scar tissue that eventually was cleared by immune system cells. After a two week  “wash-out period” of the 5-FU/Leucovorin, I entered a clinical trial testing a PARP inhibitor that targeted my gene mutation. At the point I entered the trial, I was likely already NED and probably any minimal residual disease was eliminated from the excessive chemo I had. So it was more likely the chemo is what did it and the clinical trial drug kept any new primary tumor from occurring.

I was 55 and in otherwise excellent physical condition from long-distance bike riding. My objective despite being stage IV was to attempt cure although I’m sure my team was thinking it was not likely to happen. My top priority was survival and as long as possible. It was all or nothing. I had no intention of stopping and was committed to sticking to my goal till the very end. This is why I advocated for the more aggressive approach and thankfully my team agreed to do it.

Was it doing excessive chemo, the clinical trial, a combination of the two or was there something unique about my immune system that made me what the NCI categorizes as an “exceptional responder” is not known. In those that are classified as exceptional responders, it is often observed that T-lymphocytes of a specific type can get past the fibroblast-stromal layer and penetrate deep into the tumors and work in conjunction with chemo. When I was asked if I was willing to submit to a biopsy of one of the liver mets after having such a robust response, I gave consent. There was one major problem- a review of my scans showed nothing remained to be biopsied. So what factors led to my becoming cured of stage IV remain a mystery.

From anecdotal observation of other long-term survivors that did aggressive Folfirinox or Gemzar/Abraxane, our diagnosis was made between the ages of 39-55. Most of us did significant bike riding or were runners. None of us ever smoked, did not or rarely drank, ate healthy with average BMI values and had no co-morbidities of any significance. We tolerated the chemo well and the major complaint was neuropathy.

I did develop neuropathy in the hands, fingers, balls of the feet to the toes. Sensitivity was dulled but I never lost feeling in the extremities. I always was ambulatory but did experience a loss of spatial awareness at times of where my feet were and occasionally caught the tips of my shoes when walking. I also noticed times where I was unable to walk in a straight line and tended to drift to the right. My hands and fingers cleared first followed by decreased sensitivity to cold which then resolved. That was close to one year. The feet took considerably longer. There was no improvement until 2.5 years after finishing chemo. The feet eventually resolved after 7.5 years.

Would you please share which gene mutation you have?
I understand from my visit last week at JH most extraordinary responders have BRCA .

This is very interesting. I was diagnosed with stage 4 pancreatic adenocarcinoma in March after developing a side stitch that wouldn’t go away after a run in January. My doctor has me on Nalirifox which is a variation of mFolfirinox using liposomal irinotecan instead of the irinotecan. I don’t fall into your age range as I turned 59 shortly after my diagnosis but I was a distance runner, non-smoker and always been in great health with a family history of longevity. I have only had 6 chemo sessions so far and my doctor is pleased with its results so far and my side effects have been manageable. Alas, I have no genetic mutation so a lot of the trials and target therapies are out for me. I do trust my oncologist and I know he is wanting to save my life or at least give me as long as possible. I just can’t believe a year ago I was training for my next race and my husband and I planning retirement. Your story is inspiring and and I will continue to hold on to hope.

(g)BRCA2.

Camille Moses did not have any detectable mutations in her PDAC tumor and is an exceptional responder. She is an 11 year survivor like me. I spoke on the phone with her last Friday. Was never eligible for surgery. Has a fully functioning, intact pancreas and takes no medications.
https://seenamagowitzfoundation.org/camille-moses-pancreatic-cancer-survivor/

I am curious why your doctor chose to give you the lipsomal irinotecan? Are you at a teaching hospital or is this due to drug shortages?