nanoknife IRE for pancreatic cancer

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RE: nanoknife IRE for pancreatic cancer

by bookfiler on Mon Apr 11, 2016 06:44 PM

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Peter has not had gemcitibine.  He has had twelve cycles of Folfirinox.  I will ask him if he would consider Photon therapy.  He has already had SBRT which he absolutely would not reconsider.  My thoughts are that following NanoKnife he should go on Gem/Abraxane.  I am afraid that gemzar alone is not strong enough for his fast growing tumor.   I have checked out the Photon terapy studies that you listed...it will be a hard sell to convince Peter to participate in one of them...

RE: nanoknife IRE for pancreatic cancer

by bookfiler on Mon Apr 11, 2016 06:48 PM

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Peter has not had gemcitibine.  He has had twelve cycles of Folfirinox.  I will ask him if he would consider Photon therapy.  He has already had SBRT which he absolutely would not reconsider.  My thoughts are that following NanoKnife he should go on Gem/Abraxane.  I am afraid that gemzar alone is not strong enough for his fast growing tumor.   I have checked out the Photon terapy studies that you listed...it will be a hard sell to convince Peter to participate in one of them...

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Fri Apr 15, 2016 01:04 PM

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Dear Bookfiler.

The desired radiation is PROTON therapy, not photon therapy (an example of which is SBRT).

PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Fri Apr 15, 2016 01:07 PM

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Everyone,

Here is a link to an effective, drug-free sleep method
http://jaxelection.altervista.org/downloads/SleepMethod_Phil

Patients, family and caregivers often complain of difficulty sleeping. Assuming the patient is healthy, two things are required for sleep: Tiredness AND Distraction. My paper describes how to achieve the Distraction. I have used the method successfully for 25 years.

If one is tired and can maintain this mental exercise for 15 minutes, he WILL fall asleep (assuming, of course, no extraordinary events like excessive pain or poor sleep hygiene). The key is distraction. If the tired person achieves complete distraction, he will sleep.

PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Fri Apr 15, 2016 01:28 PM

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Everyone,

The previous link to my sleep method fails because it contains a period.  Here is the correct link without the period

http://jaxelection.altervista.org/downloads/SleepMethod_Phil

PhilipJax

RE: nanoknife IRE for pancreatic cancer

by bookfiler on Fri Apr 15, 2016 02:25 PM

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On Apr 15, 2016 1:07 PM PhilipJax wrote:

Everyone,

Here is a link to an effective, drug-free sleep method
http://jaxelection.altervista.org/downloads/SleepMethod_Phil ipJax6.pdf."" target="_blank" rel="nofollow">http://jaxelection.altervista.org/downloads/SleepMethod_Phil target="_blank" rel="nofollow">http://jaxelection.altervista.org/downloads/SleepMethod_Phil

Patients, family and caregivers often complain of difficulty sleeping. Assuming the patient is healthy, two things are required for sleep: Tiredness AND Distraction. My paper describes how to achieve the Distraction. I have used the method successfully for 25 years.

If one is tired and can maintain this mental exercise for 15 minutes, he WILL fall asleep (assuming, of course, no extraordinary events like excessive pain or poor sleep hygiene). The key is distraction. If the tired person achieves complete distraction, he will sleep.

PhilipJax

Philipax,

Your link re: effective, drug-free sleep is broken.  Can check it and reshare?

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Fri Apr 15, 2016 07:17 PM

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Bookfile (and Everyone),

I was not writing to you personally, thus the salutation to “Everyone”. And, I was addressing resected patients specifically, who often lament that there are few clinical trials for them.

I then urged the resected to undergo adjuvant therapy and to find candidate therapies by

1. Contacting the major institutions, asking what therapy they use in similar cases’
2. Searching https://clinicaltrials.gov/ct2/search/advanced

Then select the best of what’s available. And, this search has to be done rapidly and assure many irons in the fire.

I then gave a list of the 3 trials I found that are available to resected patients. You might find more. One may be of interest those still helped by FOLFIRINOX: That trial offers FOLFIRINOX or some alternatives randomized.

I found the 3 by using the search terms “resected” and “pancreatic”, which sorts out 150 trials. You should review all of them and not rely entirely on me.

I gave some emphasis to PROTON therapy, so that it is not confused with the typical radiation therapy. For those whose disease has progressed on FOLFIRINOX and gemcitabine-based therapy, it is worth considering.

Finally, following IRE the battle is not over. One must be prepared for recurrence. This is a long battle, from one therapy to the next – prolonging life until the next best thing comes along.

PhilipJax

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Thu Apr 21, 2016 09:25 PM

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Everyone,

For victims of metastatic adenocarcinoma only. 42% is a very good response rate, and the one complete response is very encouraging (although the likelihood of a complete response befalling a given patient is very small).

The Phase-2 trial, taking place at 10 institutions, is still open, but will close soon, since it is taking only 80 patients.  Get details at
https://clinicaltrials.gov/show/NCT02077881

PhilipJax

Novel IDO Inhibitor Yields Durable Responses in Metastatic Pancreatic Cancer

Sandra Hanner | Published Online:3:13 PM, Thu April 21, 2016 |
http://www.targetedonc.com/news/novel-ido-inhibitor-yields-d

 

Novel therapy with indoximod, an indoleamine 2,3-dioxygenase (IDO) pathway inhibitor, in combination with standard chemotherapy, yielded a response rate of 42% as first-line therapy for metastatic pancreatic adenocarcinoma, according to results of a phase 1b study reported at the 2016 Gastrointestinal Cancers Symposium.

“The investigators are finding very interesting, prolonged responses in some patients,” said Nathan Bahary, MD, of the University of Pittsburgh Medical Center, in Pennsylvania, who presented the findings. “While we know to be cautious — as plenty of phase 1 data has been upended on phase 2 — there appears to be a signal.”

IDO an Immune Regulator

IDO is a tryptophan-catabolizing enzyme that plays a key role in the normal regulation of peripheral immune tolerance. Tumors also employ this mechanism to induce a state of immunosuppression. In cancer, IDO mediates an acquired immune tolerance towards tumors.
 
In other words, IDO allows tumors “to thwart the host immune response,” the investigators explained in their poster.
 
Indoximod is an orally available, small molecule, broad IDO pathway inhibitor that potentially interferes with multiple targets within the IDO pathway. Pre-clinical models have demonstrated synergy between indoximod and chemotherapy.
 
This phase 1b/2 study is evaluating the effect of adding indoximob to the standard-of-care regimen of gemcitabine and nab-paclitaxel (gem/nab). Researchers presented the phase 1b portion of the study at the Symposium.
 
Indoximod was escalated (600mg/1000mg/1200mg PO twice daily continuous dosing) in combination with gemcitabine (1000 mg/m2) and nab-paclitaxel (125mg/m2) weekly in the first-line metastatic setting, until disease progression. The primary endpoints were safety, toxicity, and determination of a Phase 2 dose.
 
High Response Rate
 
Fifteen patients were required to successfully dose escalate the Phase 1 study to 1200 mg twice daily. Two patients were replaced in the lowest dose cohort after rapid deterioration due to underlying disease during the regimen limiting toxicity (RLT) window.
 
The objective response rate was 42% (including one complete response), which is higher than observed in the MPACT trial of patients treated with gemcitabine/nab-paclitaxel (23%), the researchers noted.
 
The one patient with a complete response achieved this in Cycle 8. A delayed response pattern was seen in a number of patients, which is suggestive of an immune-mediated mechanism of action, Dr. Bahary said.
 
“We are seeing reductions in tumor size of 50% to 70%, and we have some phase 2 patients with ongoing responses now out to 6 months,” he said. “This is in something that has otherwise been difficult to see with immune therapies.”
“The overall response rate, observance of a complete response, and delayed and durable response patterns are promising for this combination regimen in metastatic pancreatic cancer,” the researchers noted on their poster.
 
Indoximob Well Tolerated
 
The triplet was well tolerated, investigators noted. Only one dose-limiting toxicity was observed during the study (ascites Grade 3) at the highest dose cohort. The most common adverse events (all Grade 1 or 2), regardless of attribution, were nausea, fatigue, peripheral edema, peripheral neuropathy, alopecia.
 
The Phase 2 dose was set at 1200 mg twice daily and Phase 2 enrollment (target 80 patients) is ongoing.
 
“We hope to have phase 2 interim data in time for ASCO, to see if we can confirm those delayed responses,” Dr. Bahary said.

 

 

RE: nanoknife IRE for pancreatic cancer

by zbynek on Fri Apr 22, 2016 10:48 AM

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Hello, mother of my friend undewent a sucessful nano surgery of pancreatic cancer in Czech Republic (covered by public health insurance). Her initial prognosis was "completely incurable (terminal stage)". In my contry also many alternative state-approved therapis are avlailable, which in USA or UK are not out of too strict risk-aversive regulations. Morever, the treatment is free or costs very little if you campare with usa or uk :-)Zb

RE: nanoknife IRE for pancreatic cancer

by PhilipJax on Fri Apr 29, 2016 04:41 AM

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Zbynek
Be sure to seek followup chemotherapy, not chemoradiotherapy.  See
http://www.oncologynurseadvisor.com/pancreatic-cancer/chemot

Everyone,

In this trial PF-04136309 performed well with locally-advanced patients. However, it will be months before all the results are known – the Overall Survival and Progression Free Survival, etc.

According to researchers, a future Phase-2 randomized trial will treat metastatic patients.  That trial may be a Phase 1b/2 trail, to be open soon, for previously UNtreated metastatic patients.  The Phase 2 part is randomized double-blind.  See:
https://clinicaltrials.gov/show/NCT02732938

PhilipJax

Immune-stimulating Drug and Chemotherapy Show Early Promise for Pancreatic Cancer

Megan Garlapow, PhDApril 28, 2016http://www.oncologynurseadvisor.com/pancreatic-cancer/im

A phase 1b clinical trial indicated an experimental therapy for pancreatic cancer can sufficiently control tumors to make some patients eligible for surgery.1

The study, published in The Lancet Oncology,treated 47 patients diagnosed withlocally advanced pancreatic ductal adenocarcinoma between April 2012 and November 2014. Treatment was with a standard, 4-drug chemotherapy alone (FOLFIRINOX, 8 patients) orFOLFIRINOX and an experimental, immune-stimulating drug calledPF-04136309 (39 patients).

The target of PF-04136309 is CCR2 on inflammatory monocytes. CCR2 can allow cancerous cells to evade detection by the immune system, making it easier for cancerous cells to grow and spread.

Of the patients who completed the trial with PF-04136309 (33 patients), local tumor control was achieved in 32 (97%) of them. In the PF-04136309 arm, 16 (49%) achieved an objective tumor response. One patient receiving PF-04136309 experienced acompete disappearance of tumors.

Patients in the PF-04136309 arm experienced nearlydouble the response rateof patients receiving chemotherapy alone. In the FOLFIRINOX alone arm, 5 patients received repeat imaging, though none of them achieved an objective response. Four (80%) of the 5 did achieve stable disease.

No treatment-related deaths occurred. The majority of side effects with PF-04136309 were similar to side effects with chemotherapy alone, though 3 patients in the PF-04136309 arm withdrew due to treatment toxicity.

Researchers also confirmed that PF-04136309 effectively blocked its target, CCR2.

“In summary, PF-04136309 in combination with FOLFIRINOX did not result in additional toxicity at the recommended phase 2 dose. CCR2 blockade led to a reduction in the infiltration of tumor-associated macrophages and showed evidence of an endogenous antitumor immune response,” concluded the authors.

“Our results strongly suggest that CCR2-targeted therapy affects the biology of pancreatic ductal adenocarcinoma and future clinical trials should explore this promising therapeutic strategy.”

The researchers are planning a larger, randomized,phase 2 trialwith Pfizer to assess PF-04136309 in patients withmetastatic diseaseand prognoses to survive 6 to 12 months. Pfizer is the manufacturer of PF-04136309.

Reference

1. Nywening TM, Wang-Gillam A, Sanford DE, et al. Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol. [Published online ahead of print April 4, 2016]. doi:10.1016/S1470-2045(16)00078-4.

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