nanoknife IRE for pancreatic cancer

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RE: nanoknife IRE for pancreatic cancer

by cdaley2 on Wed Feb 14, 2018 05:18 PM

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Philip, Dr. O'Reilly  will request the CPI_613 on compassionate basis. However, the form says you must be folfirinox naive, which doesnt seem very compassionate to me!. My scan after 8 FOLFORINOX sessions shows mostly stability but slight growth in a couple. So while the Folfirnox is doing something, it's not gangbusters. If I can't get the 613, will go to Gem/Abrax, to which she agreed to at Cisplatin and Vitamin D as per Honor Health protocol.

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Thu Feb 15, 2018 04:15 AM

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Nab-Paclitaxel + Gemcitabine Upgrades
Benefits to adding Cisplatin, Nivolumab, Paricalcitol, Anakinra

Dear CDaley2,
          My posts are usually delayed by the forum system for 2 days, due to the links.
          Regarding CPI-613, I agree, not very compassionate.  The compassion may have taken place BETWEEN trials.  But, now that the manufacturer has a Phase 3 trial, it probably wants all CPI-613 use to conform to that trial.  Another patient informs me that Compassionate Use is also limited to USA and Israel.
          Regarding Cisplatin, you are an excellent advocate for yourself.  You’re proof of the Rule: Patients will not get special treatment unless they press for it.  You are likely to have good fortune.  Misfortune comes to those who are passive, lack skepticism and fail to do the hard work of medical journal research.
         Some other therapy options to consider. Monitor your new chemo regimen frequently, hopefully with PET. If there are problems, immediately consider a further modification of the Nab-P+Gem+Cisplatin regimen. As you know, time is an enemy.

>>> Perhaps switch to the components of the following regimen (an Honor Health design): Gemcitabine, Nab-Paclitaxel, Cisplatin, Nivolumab and Paricalcitol, if your oncologist can be persuaded.
          See Abstract 358 of the 2018 GI Cancers Symposium, which showed, for 10 patients, a Response Rate of 80% and a Disease control rate of 100%, which is Partial Response (80%) plus Stable Disease (20%).  See
http://clinicaltrials.gov/show/NCT02754726
         All the agents are available. Paricalcitol, similar to a Vitamin D2 analog, treats hyperparathyroidism.

>>> Perhaps switch to the components of the following regimen: Gemcitabine, Nab-Paclitaxel, Cisplatin and Anakinra.  You are almost there already.
          See GI Symposium Abstract 449.  Anakinra is a readily available arthritis drug.  For 13 months no patient developed metastases while treated with this regimen.
https://clinicaltrials.gov/ct2/show/NCT02550327

          Note that most of the well-performing regimens, presented at 2018 GI Cancers Symposium, contain Cisplatin, if the backbone was initially Nab-P+Gem.  The abstracts are here:
http://jaxelection.altervista.org/pancreatic/2018ASCOGICance
         PhilipJax

PS: Often, oncologists make a God’s judgment: Shall I make every effort to treat this patient responsible and cleverly, which might help her somewhat but postpone the inevitable, or should I use this life in an uncertain trial which may help all mankind?
         Frequently, they push the patient into the trial without telling her the grave uncertainties. And, sometimes these oncologists oversee trials which need experimental subjects – that conflict-of-interest is unethical and frequent.

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Wed Feb 21, 2018 01:51 PM

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Third-Line Chemotherapy Regimens
What to Use When the 1st & 2nd Lines Fail
Or, How to Plan the Sequence

Everyone:
          There is a great need for Third-Line therapies for Pancreatic Adenocarcinoma.  So, I have tried to gather what is known.
          The NCCN guide does not address the subject, although, its Evidence Block section (around page 4 and around pages 39-44) offers information on the performance of numerous chemo regimens, some of which are non-mainstream.
          But for Third-Line therapy, NCCN merely suggests clinical trials, which is not helpful.  If a clinical trial is sought, it is wise to choose a combination which adds an experimental therapy to a known core regimen.  It is very unwise to select a trial whose components have NOT been tested in human trials, whose performance numbers (Response Rate, Progression Free Survival and Overall Survival) are unknown.
          The NCCN guidelines can be found via this link.  And, I will post the 2018 edition when it is published in a few weeks.
http://jaxelection.altervista.org/pancreatic/NCCN3.2017Pancr
          The following 2016 German article offers some reasonable options for Third-Line agents.  And, the article’s Therapeutic Algorithm (Figure 6), available here in a cleaner format, offers many alternatives for each of the three treatment lines.
http://jaxelection.altervista.org/pancreatic/3rdThirdLine201
http://jaxelection.altervista.org/pancreatic/TherapeuticAlgo
          The Figure 6 algorithm repeats Gemcitabine in two different lines with some success.  And, the authors rely frequently on Erlotinib (an EGFR tyrosine kinase inhibitor) for part of a Third Line therapy, although other targeted therapies, for example Refametinib, might be used in the pair.
          In one Figure 6 path (G/P, G+E, C+E) Oxaliplatin might be added to G+E for more impact.  And, Cisplatin might be added to G/P in at least two treatment paths (G/P, G+E, C+E and G+E, G/P, C+E).  More on Cisplatin below.
          In addition, the tables of the following document give comparative data on KNOWN agent combinations.  The table data provide only a rough comparison, because patient groups often have different physical conditions and different therapy failures.
http://jaxelection.altervista.org/pancreatic/14_TargetedTher
          Some additional Third-Line regimens are discussed during the following interview with oncology leaders.
http://jaxelection.altervista.org/pancreatic/GoodTranscript_
          Found in other oncology journals is the regimen series: Gemcitabine+Nab-Paclitaxel, then Nal-IRI+5FU, then FOLFOX – which assures that each key agent (Gemcitabine, Irinotecan and Oxaliplatin) is used only once.  However, FOLFOX is a relatively ineffective regimen.  So, a better one, also containing Oxaliplatin, might be preferred for the Third-Line.
          Nevertheless, FOLFOX did well when combined with AM0010.  See
http://jaxelection.altervista.org/pancreatic/AM0010+FOLFOX_2017GastrointestinalCancersSymposium.doc
http://jaxelection.altervista.org/pancreatic/AM0010+FOLFOXMetastatic2017.pdf
          The GTX regimen (Gemzar® Gemcitabine, Taxotere® Docetaxel, Xeloda® Capecitabine) has also performed fairly well, and, according to one trial report, “survival did not correlate with the number of prior regimens,” meaning that its effectiveness did not seem affected by prior chemotherapy.
          Component dosages for the core chemo regimens are detailed in this document:
http://jaxelection.altervista.org/pancreatic/Pancreatic2017T
          In addition, when Gemcitabine+Nab-Paclitaxel is used, it may be wise to add Cisplatin, and perhaps other agents.  See this document.
http://jaxelection.altervista.org/pancreatic/AddCisplatinToGem+NabPaclitaxel2017.doc
          The addition of Cisplatin (and other agents) is described in Abstracts 358 and 449 of the 2018 Gastrointestinal Cancers Symposium, which report very good performance due to the additions of Cisplatin, Nivolumab, Paricalcitol and Anakinra to Gemcitabine+Nab-Paclitaxel.  However, the test groups were small creating less reliability.
          The two abstracts can be found in the following document.  Each abstract gives a link to its clinical trial website, so you can determine the agent dosages.
http://jaxelection.altervista.org/pancreatic/2018ASCOGICance
         PhilipJax

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