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nanoknife IRE for pancreatic cancer

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RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Mon Dec 09, 2019 04:52 AM

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BL-8040 Performs Well For Metastatic Patients

          At the upcoming December 11-14, 2019 ESMO Immuno-Oncology conference in Geneva, researchers are expected to report good performance for experimental BL-8040, a mobilizer of immune cells and a CXCR4 antagonist.
          CXCR4 is directly involved in tumor progression and is over-expressed in more than 70% of human cancers.
          In its December 05 announcement BL-8040’s manufacturer states that 4 of 15 evaluable metastatic patients experienced a Partial Response, suggesting a 27% Response Rate, good performance for these second-line patients who have already failed a first-line chemotherapy.  53% experienced Stable Disease.
          The median Overall Survival and median Progression Free Survival are not yet known.  See
https://finance.yahoo.com/news/biolinerx-announces-prelimina
          A Partial Response is a decrease of at least 30% in the sum of the largest dimensions of target lesions – a decrease usually determined by radiology.
          These preliminary results come from the triple combination arm of the ongoing Phase 2a COMBAT/KEYNOTE-202 trial which uses BL-8040 plus Pembrolizumab (Keytruda®) plus liposomal irinotecan (Onivyde®)/5-fluorouracil/leucovorin (5-FU/LV).  The other experimental arm combines BL-8040 with Pembrolizumab.
          The trial expects to recruit 80 participants at approximately 25 locations, principally in the USA and Spain.  The trial is still recruiting patients.  It is non-randomized, so all patients receive one of the two drug combinations.  The trial description is found here
https://clinicaltrials.gov/show/NCT02826486
          Be sure to study my new Decision Guide available here.
http://pancreatic.altervista.org/
          After careful study you will know what therapies are available for your stage of disease; how to select clinical trials; how to avoid wasted time, and much more.  Read it NOW.  This disease is a swiftly moving parade.  If an opportunity is bypassed now, you will not be able to return later to claim it.
         PhilipJax

 

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Fri Jan 10, 2020 05:30 AM

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Fungi & Bacteria Promote Pancreatic Cancer
New Breakthrough Research

Everyone:
          I rarely draw attention to pre-clinical studies (whose test subjects are not humans).  However, two reports, a fungi article published 02Oct2019 and a bacteria report published 22Mar2018, reveal that specific fungi and specific bacteria independently promote pancreatic cancer growth.
         They are conditions which you can address to enhance your survival prospects.  See
http://pancreatic.altervista.org/downloads/FungalCreatesPCRi
http://jaxelection.altervista.org/pancreatic/CertainBacteria
          The landmark animal research, led by New York University schools of medicine and dentistry (as well as City University of New York for the fungi study), made several extraordinary discoveries, specifically:

1. Role of Fungi.  The 2019 research article reported that “PDA tumours in humans and mouse models of this cancer displayed an increase in fungi [principally Malassezia] of about 3,000-fold compared to normal pancreatic tissue.  Fungi migrate from the gut . . . to the pancreas, and this is implicated in the pathogenesis of PDA.”  PDA is Pancreatic Ductal Adenocarcinoma.
          Researchers determined that “Inflammation induced by oncogenic KRAS leads to fungal dysbiosis, which in turn promotes tumour progression.”
          In an effort to determine causation and to identify a therapy, researchers introduced the antifungal agent Amphotericin B and found that “Ablation of the mycobiome [using Amphotericin B] was protective against tumour growth in slowly progressive and invasive models of PDA.”  A mycobiome is a fungal community in or on an organism, including animals and humans.
          These observations were achieved by analysis of the faecal and tumour mycobiome in human patients with PDA, and in mice.  Find the research report here:
http://pancreatic.altervista.org/downloads/FungiPromotePC201

2. Role of Bacteria.  The 2018 research article reported that “Pathogenic gut bacteria migrate to the pancreas through the pancreatic duct” where they “change the immune environment around cancer cells to let them grow faster.”
          These bacteria, specifically “proteobacteria, actinobacteria, and fusobacteria” “shut down the immune reaction to cancer cells.”  In the test animals “eliminating the bacteria using antibiotics restored the ability of immune cells . . . into immune-suppression.”
          Researchers determined that the addition of oral antibiotics increased threefold the efficacy of checkpoint inhibitors, a form of immunotherapy.  Find the research report here:
http://jaxelection.altervista.org/pancreatic/MicrobiomePromo
          The 2018 bacteria study has resulted in clinical trial at Perlmutter Cancer Center, to test whether a combination of antibiotics (ciprofloxacin and metronidazole) can improve the effectiveness of a checkpoint inhibitor, an anti-programmed death receptor 1 (PD-1) antibody.  Given the elapsed time, the enrollment status is probably “Not Recruiting.”
          Likely the 2019 fungi study will generate a clinical trial as well.

         There is a lesson here. If you are not responding significantly to chemotherapy, do not wait for a future trial. Consider asking that you betested for these microbes, and, if the harmful mycobiome (fungi) or microbiome (bacteria) patterns are present, seek suitable therapy to counter the condition. Most people do not survive this disease. You have little to lose.

          Another note about bacteria: In an earlier 2017 article researchers reported that bacteria MAY explain why some pancreatic patients respond poorly to Gemcitabine.
          The 15Sep2017 research report, prepared by Israeli and MIT scientists, suggests that bacteria within pancreatic tumors can thwart Gemcitabine, a key therapy agent.  The culprit is bacteria equipped with the long form of the CDD gene.
          Tests, conducted in lab animals, demonstrated that antibiotics could suppress the unwanted bacteria and make Gemcitabine active again.  The report is at
http://jaxelection.altervista.org/pancreatic/BacteriaThwartC
          Further, it has been widely suspected for years that bacteria from periodontal disease of the gums are a contributing factor to pancreatic cancer.

          Finally, you will do well to download my Decision Guide which addresses all stages of the disease, and the available therapies for each disease stage, including Thirid-Line therapies.  Two days of hard study, and you will be up to date.  The Guide is available at the following site, upper-right corner:
https://pancreatic.altervista.org/
         PhilipJax

 

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Sun Feb 09, 2020 01:48 PM

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2020 Gastrointestinal Cancers Symposium
Installments, Part 1

Everyone,
          Today, I begin reviewing abstracts from the 2020 GI Cancers Symposium which was held January 23-25, 2020 in San Francisco.  There are at least 50 relevant abstracts; so, over a period of several days or weeks, I will cover the “best”.  If you can’t wait, the abstracts are found here:
http://pancreatic.altervista.org/downloads/GI20PancreaticCan
          The order in which I present the abstracts does NOT signify their importance.  I am merely beginning with the first abstract meeting my search criteria.
          Be sure to study my Decision Guide, downloadable at
http://jaxelection.altervista.org/pancreatic/PJaxDecisionAlg " target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/PJaxDecisionAlg
         PhilipJax

Abstract 638: HALO 109-301: A randomized, double-blind, placebo-controlled, phase 3 study of pegvorhyaluronidase alfa (PEGPH20) + nab-paclitaxel/gemcitabine (AG) in patients (pts) with previously untreated hyaluronan (HA)-high metastatic pancreatic ductal adenocarcinoma (mPDA).
          Hyaluronan (HA) is a significant component of the tumor microenvironment.  Because the experimental agent PEGPH20 degrades HA, it was hypothesized that PEGPH20 (P), if added to chemotherapy NabPaclitaxel (A) + Gemcitabine (G), would create an effective combination treatment (PAG).
          An earlier Phase 2 PAG trial showed promising results, so researchers at a dozen centers undertook a Phase 3 trial (NCT02715804) employing 494 patients randomized 2:1 to PAG or placebo+AG.  Unfortunately, the results were disappointing:
1. The addition of PEGPH20 did not improve clinical outcomes . . . ,” according to researchers.
2. Median Overall Survival for PAG vs AG was 11.2 vs 11.5 months, and median Progression Free Survival was 7.1 vs 7.1months.
         This is a humbling reminder that early phases of research yield uncertain results and that a therapy’s performance is known only after large-scale Phase 3 trials.

Abstract 651: Improved surgical margins with neoadjuvant versus adjuvant chemotherapy in clinical stage I resectable pancreatic adenocarcinoma: A National Cancer Database study.
          For initially resectable patients USA researchers found more evidence supporting NeoAdjuvant Therapy (NAT) before surgery, rather than initial surgery followed by Adjuvant Therapy (AT).
          Researchers, after reviewing the records 10,453 patients in the National Cancer Database, concluded the following:
1. NAT patients had significantly higher margin negative resection rates (84.5%) than AT patients (79.4%).”  A margin negative (or negative margin) is far more desirable than a positive margin.
2. Overall, total or partial NAT for clinical Stage I resectable PA (pancreatic adenocarcinoma) provides a better chance for margin negative resection.”

Abstract 664: Comparing survival outcomes for neoadjuvant therapy versus adjuvant therapy in the management of stage 1 pancreatic adenocarcinoma: A National Cancer Database study
          A second National Cancer Database survey also sought to learn which strategy is better: Surgery-First followed by Adjuvant Therapy (AT) or NeoAdjuvant Therapy (NAT) first followed by surgery
          Using the National Cancer Database 5 Milwaukee institutions identified 9,017 patients who underwent surgical resection of Stage 1, 1A, and 1B disease and arranged them into two groups (AT and NAT) to assess outcomes.  7453 patients had surgery followed by AT; and 1564 pts had NAT followed by surgery.  The study yielded the following findings:
1. “90-Day Mortality was 0.35% in the AT group compared to 0.83% in the NAT group.”
2. “Median [Overall] survival was 28.5 (26.5-29.9) months in the NAT group, compared to 25.4 (24.7- 26.1) months in the AT group.”
          NAT was associated with increased overall survival; however, the increase was moderate.  And, NAT was associated with an increased 90 day mortality.
         Consider a strategy: Patients rarely have an opportunity for surgical resection. So, if you chose NAT over immediate resection, undertake CA19-9 and CT monitoring within one month. If improvements are not dramatic, consider shifting to resection without delay.

Abstract 657: Survival outcomes based on sequence of therapy using FOLFIRINOX and nab-paclitaxel + gemcitabine in metastatic pancreatic ductal adenocarcinoma
          It has been a vital question for metastatic patients: Which chemotherapy SEQUENCE is better, FOLFIRINOX (FFX) then Nab-Paclitaxel + Gemcitabine (AG), or AG then FFX.  To learn which sequence is better American researchers reviewed the records of 3,042 patients in the National Cancer Database.  The research outcome:
          For patients who received both FFX and AG, median Overall Survival was similar, regardless of the sequence . . . Median Overall Survival for patients treated with first-line FFX and second-line AG versus first-line AG and second-line FFX was not significantly different (12.0 vs. 12.5 months)”
          In a week or so the next 2020 GI Symposium installment will be posted.
          Be sure to study my downloadable Decision Guide.  Within a few days of hard work you will understand how to approach this terrible disease, based on your disease stage – and learn what therapies work and which ones don’t.  The Guide is downloadable at
http://jaxelection.altervista.org/pancreatic/PJaxDecisionAlg " target="_blank" rel="nofollow">http://jaxelection.altervista.org/pancreatic/PJaxDecisionAlg
         PhilipJax

 

RE: nanoknife IRE for pancreatic cancer

by Mkk2018 on Mon Feb 10, 2020 08:11 PM

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We are semi in this boat now. Treated with FFX, 22 rounds, followed by lynparza, and then low hemoglobin and some progression. Now progression and put on GYX Chemo and no lynparza. We are wondering about immunotherapy? . Any input or experience ? We are 16 months into this battle with stage 4, PanCAN.

RE: nanoknife IRE for pancreatic cancer

by DavesGirl70 on Mon Feb 10, 2020 08:20 PM

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On Feb 10, 2020 8:11 PM Mkk2018 wrote:

We are semi in this boat now. Treated with FFX, 22 rounds, followed by lynparza, and then low hemoglobin and some progression. Now progression and put on GYX Chemo and no lynparza. We are wondering about immunotherapy? . Any input or experience ? We are 16 months into this battle with stage 4, PanCAN.

Hey there, sounds like we have similar stories. My partner was diagnosed October 2018 (so we are also 16 months in), stage 4 with mets to liver, had FFX 14 rounds (last one was July 2019), then he tested positive for germline BRCA 1 mutation and started Lynparza Aug 2019 which has so far been keeping things stable (no progression yet, fingers crossed) but he has had low hemoglobin to the point where he's needed blood transfusion on 2 occasions. Wondering how long on Lynparza before you experienced progression? Did you have a positive BRCA test? Did you progress on FFX before switching to Lynparza (wondering why you didn't go back to FFX after lynparza before going to GYX)? PanCan org is an excellent resource for clinical trials, Craigs Cause too - if you give them some info they will do searching for you. I have seen combinations of lynparza with chemo. Immunotherapy seems to be successful in rare cases - seems to be the exception not the rule - but there are lots of studies now with different chemo combos that might be accessible as well. Our oncologist also told us about another drug coming up soon (not sure what that means, if in trials yet or not) that will benefit BRCA positive patients.

Sending you hugs, this is the worst boat to be in.

RE: nanoknife IRE for pancreatic cancer

by Mkk2018 on Mon Feb 10, 2020 08:28 PM

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Hi! We had minor progression on the FFX we are pretty sure. And about 3 months on lynparza before very low hemoglobin. However we had 2 ablation treatements while on lynparza so that may have affected things as well? What is the new drug ? Do you have any information on it ? I’m wondering thjufh if going back on FFX might be the best option. We just had heard of some immunotherapy but again not a lot of overall success ...

RE: nanoknife IRE for pancreatic cancer

by DavesGirl70 on Mon Feb 10, 2020 08:37 PM

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On Feb 10, 2020 8:28 PM Mkk2018 wrote:

Hi! We had minor progression on the FFX we are pretty sure. And about 3 months on lynparza before very low hemoglobin. However we had 2 ablation treatements while on lynparza so that may have affected things as well? What is the new drug ? Do you have any information on it ? I’m wondering thjufh if going back on FFX might be the best option. We just had heard of some immunotherapy but again not a lot of overall success ...

Interesting re: ablation treatments! Can't say I know much about that (yet).

He also experienced very low hemoglobin starting in November - it got as low as 62 at one point. A 4 week break and then lowering the dose to 200/day instead of 300 seems to be keeping it normal now. I haven't heard of what it might be called. I'm just reading through the abstracts that PhilipJax linked now - I'll definitely keep you posted if I see anything promising or worth asking about! I have seen veliparib as another parp inhibitor similar to lynparza in combination with GYX - wonder if that might be worth asking about? AbbVie seems to be the company/org that does immunotherapy trials but it might be better to ask PanCan or Craigs Cause about clinical trials because they have a team of scientists and doctors who look them up for you. If FFX was keeping things relatively stable then that might be an option to consider if GYX stops/isn't working. Did you have any germline mutations i.e. BRCA?

RE: nanoknife IRE for pancreatic cancer

by Mkk2018 on Mon Feb 10, 2020 08:43 PM

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We had hemoglobin at 53 also. So we did transfusions. I am going to look at those option you posted. But also keep me posted as well. we started Lynparza when things changed so maybe going back to it if they settle is the option. We were told lynparza with chemo could be fatal ?

RE: nanoknife IRE for pancreatic cancer

by Mkk2018 on Mon Feb 10, 2020 08:44 PM

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Sorry. Also meant to say yes - BRCA 2 positive !

RE: nanoknife IRE for pancreatic cancer

by DavesGirl70 on Mon Feb 10, 2020 08:49 PM

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On Feb 10, 2020 8:43 PM Mkk2018 wrote:

We had hemoglobin at 53 also. So we did transfusions. I am going to look at those option you posted. But also keep me posted as well. we started Lynparza when things changed so maybe going back to it if they settle is the option. We were told lynparza with chemo could be fatal ?

Ask about veliparib instead (different from Lynparza, but same class of drug) - it has been used in combination with a variety of chemotherapies

One example: https://www.thelancet.com/article/S2352-3964(18)30637-6/fulltext 

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