nanoknife IRE for pancreatic cancer

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RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sun Nov 18, 2018 01:28 PM

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CAR-T For Liver Metastases
Good Effect When Delivered Under Pressure

Everyone:
          For Stage 4 pancreatic patients the presence of liver metastases makes them ineligible for surgical resection and possible cure.
          In a new development researchers recently presented data on immunotherapy for liver metastases: Anti-CEA CAR-T delivered using a new form of Hepatic Arterial Infusion (HAI) called Pressure-Enabled Drug Delivery (PEDD).  The event was the Society for Immunotherapy of Cancer (SITC) Annual Meeting, November 7-11, 2018.
          The exceedingly small Phase 1b trial treated 4 pancreatic patient and one colorectal cancer patient.  These are the findings:
1. After treatment 2 of 4 (50%) pancreatic patients experienced Complete Responses (CR), no viable liver metastases as determined by PET scan.  One of the two is still alive after 19.3 months; the other did not do so well.
2. The more successful CR patient had undergone only one prior treatment regimen (FOLFIRINOX) and received a second CAR-T infusion 13 months after the first dose.  The other CR had undergone 6 prior chemo regimens.  They suffered 7 and 6 liver metastases, respectively.
3. For pancreatic patients the Median Overall Survival (OS) was 8.4 months.
4. PEDD significantly increased CAR-T more than five-fold within liver metastases, when compared with low-pressure microcatheters.  PEDD direct-delivery overpowers the high pressure within solid tumors and avoids the severely limiting side effects of systemic therapy such as neurotoxicity.  
          Unfortunately this trial NCT02850536 is no longer recruiting.  However, the next trial phase could start within a year.  Contact the trail leaders.  See
https://clinicaltrials.gov/ct2/show/NCT02850536
          The press release can be found here:
http://jaxelection.altervista.org/pancreatic/SorrentoCAR-T_S
          And, the detailed SITC poster presentation can be found here:
http://jaxelection.altervista.org/pancreatic/AntiCEA_CAR-T_H
          For more information on CAR-T therapy for pancreatic cancer download this article:
http://jaxelection.altervista.org/pancreatic/CAR-TPotentialP
          For more Pancreatic Cancer treatment information and a Decision Guide visit my website at
https://pancreatic.altervista.org/
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by Baloo on Mon Nov 19, 2018 03:48 PM

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Philipjax, thank you. As always your invaluable posts give hope to those of us that really, really need it.

RE: nanoknife IRE for pancreatic cancer

by saint_123 on Fri Nov 23, 2018 05:33 PM

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Phase 1b and a sample size of 4. Nevertheless, something to keep an eye on I suppose.

Can't thank you enough for your contribution in bringing the latest in research to this forum.

RE: nanoknife IRE for pancreatic cancer

by caseyzson on Thu Dec 06, 2018 05:05 PM

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Hi PhillipJax,

I looked on your decision guide and also this site, but it is hard to search - I was wondering what your thoughts of local Y90 radiation for the treatment of liver metastsis.  This is meant to hopefully extend the time for other new trials to join: 

http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.e15

Rest of the cancer is stable.

Thank you!

RE: nanoknife IRE for pancreatic cancer

by caseyzson on Thu Dec 06, 2018 05:14 PM

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Please disregard, this question was already answered earlier.  Seems Proton is one of the better options..apologies.

RE: nanoknife IRE for pancreatic cancer

by TeamSammy on Thu Dec 13, 2018 04:57 PM

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On Nov 18, 2018 1:28 PM PhilipJax wrote:

CAR-T For Liver Metastases
Good Effect When Delivered Under Pressure

Everyone:
          For Stage 4 pancreatic patients the presence of liver metastases makes them ineligible for surgical resection and possible cure.
          In a new development researchers recently presented data on immunotherapy for liver metastases: Anti-CEA CAR-T delivered using a new form of Hepatic Arterial Infusion (HAI) called Pressure-Enabled Drug Delivery (PEDD).  The event was the Society for Immunotherapy of Cancer (SITC) Annual Meeting, November 7-11, 2018.
          The exceedingly small Phase 1b trial treated 4 pancreatic patient and one colorectal cancer patient.  These are the findings:
1. After treatment 2 of 4 (50%) pancreatic patients experienced Complete Responses (CR), no viable liver metastases as determined by PET scan.  One of the two is still alive after 19.3 months; the other did not do so well.
2. The more successful CR patient had undergone only one prior treatment regimen (FOLFIRINOX) and received a second CAR-T infusion 13 months after the first dose.  The other CR had undergone 6 prior chemo regimens.  They suffered 7 and 6 liver metastases, respectively.
3. For pancreatic patients the Median Overall Survival (OS) was 8.4 months.
4. PEDD significantly increased CAR-T more than five-fold within liver metastases, when compared with low-pressure microcatheters.  PEDD direct-delivery overpowers the high pressure within solid tumors and avoids the severely limiting side effects of systemic therapy such as neurotoxicity.  
          Unfortunately this trial NCT02850536 is no longer recruiting.  However, the next trial phase could start within a year.  Contact the trail leaders.  See
https://clinicaltrials.gov/ct2/show/NCT02850536 "" target="_blank" rel="nofollow">https://clinicaltrials.gov/ct2/show/NCT02850536 " target="_blank" rel="nofollow">https://clinicaltrials.gov/ct2/show/NCT02850536
          The press release can be found here:
http://jaxelection.altervista.org/pancreatic/SorrentoCAR-T_S tage406Nov2018.doc"" target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/SorrentoCAR-T_S target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/SorrentoCAR-T_S
          And, the detailed SITC poster presentation can be found here:
http://jaxelection.altervista.org/pancreatic/AntiCEA_CAR-T_H epaticInfusion2018HiLite2.pdf"" target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/AntiCEA_CAR-T_H target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/AntiCEA_CAR-T_H
          For more information on CAR-T therapy for pancreatic cancer download this article:
http://jaxelection.altervista.org/pancreatic/CAR-TPotentialP ancreatic2018USA2166.pdf"" target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/CAR-TPotentialP target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/CAR-TPotentialP
          For more Pancreatic Cancer treatment information and a Decision Guide visit my website at
https://pancreatic.altervista.org/ "" target="_blank" rel="nofollow">https://pancreatic.altervista.org/ " target="_blank" rel="nofollow">https://pancreatic.altervista.org/
         PhilipJax

Phillip- 

Thank you for this wonderful information. My Dad has panc cancer with liver mets. How can one tell if their liver lesions are "CEA-expressing"? We've done the "Know Your Tumor" testing and have his mutations listed, but I don't see any info on his report related to CEA. Thanks for your help!

Andrea

RE: nanoknife IRE for pancreatic cancer

by caseyzson on Thu Dec 13, 2018 09:31 PM

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Andrea, not to take PhillipJax away from answreing, but if your dad tested for CEA along with CA-19-9?  CEA is a tumor marker that is expressed in the blood, my mother gets this tested with her blood every time she goes in.  I've read that just as some PC patients don't express CA-19-9, some do not express CEA as well...but that most do.  I would wait for Phillip to confirm this though.

Also, in other news, it looks like tamoxfien, the breast cancer drug, is back in the news again as it COULD be helpful with PC, and new science behind why: https://medicalxpress.com/news/2018-12-breast-cancer-drug-ch

It was already tested in small phase 1/2 trials and shown it could have some benefit: https://www.ncbi.nlm.nih.gov/pubmed/12174927

PhillipJax, any thoughts on Tamoxifen?  It's a cheap drug that can be used today - some human data exists so wondering if you think it would be something to ask oncolgist about if you are in 3rd / 4th line as we are.

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Fri Dec 14, 2018 04:11 AM

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Tamoxifen & Animal Studies

Andrea & Everyone:
          Caseyzson has done a fine job describing CEA testing.
          You should examine therapies beyond the pressurized CAR-T therapy which I have described in the post above.  You need to spend about 2-3 days of thorough study using my website and Decision Guide.  That will bring you up to date.
          And, of course, the pressurized CAR-T won’t be available for awhile.  The EndPC website is here:
https://pancreatic.altervista.org/
          Regarding the agent Tamoxifen, the recent press release, cited above, describes animal research.  And, animal response rarely translates to human subjects.  At my website read the section on clinical trial selection and animal research, right-side bottom.
          You will learn that in the past 20 years only about 4 trials have led to regimens used today in clinical practice.  Hundreds of trails failed, sacrificing thousands of desperate patients.  Yet, the hundreds of failures were based on successful animal studies.
          In the Phase 2 trial, linked above and reported in 2002, Tamoxifen is combined with Gemcitabine.  The resulting Response Rate is 11%, which is not great and which is approximately the Response Rate for Gemcitabine alone.
          The website and Decision Guide identify available and emerging regimens which have better NUMBERS.  And there you will learn how to use the NUMBERS to select the best therapies.
          And be sure to read my post of months ago evaluating the “Know Your Tumor” program.
          The ASCO symposia begin again in early 2019.  So, we may learn of additional new potent therapies then.
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sat Dec 15, 2018 02:04 PM

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Adjuvant Therapy NOT Needed
For Resected <1cm (T1a/T1b) Tumors

Everyone:
         For pancreatic cancer victims one can only hope for a tumor <1cm in size.  But, in such a case adjuvant therapy (chemotherapy or radiation following surgery) may offer no benefit.
          Using the National Cancer Data Base researchers at Emory University reviewed the records of 876 patients and found the following via statistical analysis:
1. “The median OS was significantly different for patients who received adjuvant therapy [following surgery] compared with patients who did not (70.7 months vs 46.9 months).”
2. However, “for patients with [resected] tumors measuring <1 cm (there was) no survival benefit for adjuvant therapy.”
          Of course this applies to tumors limited to the pancreas and less than (<) 1cm in the greatest dimension.  It might also be presumed that the surgical margins must be negative.
          Such T1a/T1b tumors are too rare.  Of 876 patients, whose pancreas-only tumors measured <2cm, only 30% had tumors <1cm (Stage T1a/T1b).
          The November 2018 report can be found here:
https://www.ncbi.nlm.nih.gov/pubmed/30457666
https://doi.org/10.1002/cncr.31787
         PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Mon Jan 14, 2019 04:20 AM

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Therapy for Borderline Resectable & Locally Advanced
It is claimed that Neoadjuvant FOLFIRINOX is better than surgery

Everyone:
          This posting deals with conditions other than metastatic.
          New research challenges somewhat the standard treatment pattern.
          “Using published and institutional clinical data,” researchers in Boston and New York concluded that neoadjuvant (pre-surgery) FOLFIRINOX is a better option than surgery plus adjuvant (post-surgery) therapy for Borderline Resectable (BR) and Locally-Advanced (LA) cases.
          Their decision-analysis calculated that the median OS was best with nFOLFIRINOX (34.5 months) vs surgery plus GEM/CAPE (28.0 months) vs surgery plus Gemcitabine (22.0 months.  And, Median DFS was also better with nFOLFIRINOX: 15.0 months vs 14.0 months vs 13.0 months, respectively.  Gem/Cape means Gemcitabine plus Capecitabine, and DFS means Disease Free Survival, similar to Progression Free Survival (PFS).
          This finding diverges greatly from the optimal model of using IRE plus surgery to managed Locally-Advanced disease, followed by modified FOLFIRINOX (mFOLFIRINOX), if the patient can tolerate that adjuvant regimen (otherwise maintenance therapy Gemcitabine plus Capecitabine might be employed).  See my previous posts and my website on adjuvant mFOLFIRINOX and maintenance therapy.
          The 2018 Boston-New-York report can be found here:
http://theoncologist.alphamedpress.org/content/early/2018/12
          As mentioned earlier, the study did not considered the new paradigm which employs adjuvant mFOLFIRINOX following surgery.  See a previous post on adjuvant mFOLFIRINOX in this forum and at my website.  There you can also download and study the very useful Decision Guide.  See
https://pancreatic.altervista.org/
          The ASCO symposium on pancreatic cancer takes place in January 2019.  So, in a few weeks I will present an analysis of the more useful and favorable research.
         PhilipJax

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