CTIX Stock Alert 08/11/2014 05:51:17 $CTIX Thanks
Post# of 64137
Posted On: 08/11/2014 6:51:22 AM
CTIX Stock Alert 08/11/2014 05:51:17 $CTIX
Thanks for that!!
Good Morning, CTIX!
Great post thank you for sharing.
Have a great week everyone!
Oh yes it it! Flying in and out of there all the time. I'll take us to the party lol!
Calculations based on formulas in article cited earlier:
http://www.fasebj.org/content/22/3/659.full
I just plugged in numbers.
No doubt, intraperitoneal dosing likely has some very real advantages over IV administration, especially for intraabdominal tumors. Advantages include slower absorption and higher intraperitoneal drug levels. To achieve therapeutic serum levels to treat most tumors, I think modifying the intravenous protocol would be more controllable and preferable to intraperitoneal injection.
ROMAD Diver - You made me "snort" with laughter while eating a brownie, damned near choked but it was worth it!
I just found out from a secret source that found out in a meeting of secret people talking about secret stuff that they discovered Dr. Menon's secret ingredient used in Kevetrin. It ends up the secret ingredient is Chuck Norris DNA! Expect the news to come out sometime this week, and the share price to be somewhere in the $2,000,000,000 per share range.
DISCLAIMER! In order to relieve some of the tension on this board, this was meant as a joke. Do not trade based on this information--Chuck Norris DNA is unharvestable.
Thanks for the links KMBJN - it would appear from the abstracts they don't think BSA is the end all either and feel "alternatives based on fundamental principles of clinical pharmacology" are more appropriate. Lots of variables....... With regards to the vancomycin use, my daughter confirmed they use it a lot for back surgeries but not brain since there are concerns about ototoxicity. A study I read about vancomycin powder concluded "it doesn't cut infection post spine surgery as noted here:
http://www.empr.com/vancomycin-powder-doesnt-...le/324883/
But who am I to say....... maybe it makes the docs feel better that they are being "thorough".......
Do you have a source for that?
I found one thing ( http://www.medscape.com/viewarticle/780560) that seemed to indicate IP was superior to IV. I'm not exactly an expert so I don't know how this, if at all, would translate to our case.
Thanks for the insight that takes mouse dose administration verses human IV into account.
Hi biodoc, excellent observation! Never considered the serum level differences between intraperitoneal vs intravenous. Great first post, stop in more often.
I'll access the article below from my office tomorrow and see what McGonicle and Ruggeri (2014) have to say, but seems they advocate hierarchical data sets that may include Bayesian inference (Multi Treatment Comparisons) and Markov chain Monte Carlo. If anyone can access this, please feel free to do so and report.
Animal models of human disease: Challenges in enabling translation
http://www.sciencedirect.com/science/article/...5213004929
Looks like Dr. Menon's team is not using simple arithmetic modeling involved in Baur conversions except as a guide for starting dose, as noted by you and others.
I don't know if you are right, but your calculations, evaluation, and interpretation certainly make sense. Thank you for chiming in. I will look forward to seeing more of your posts in the future.
biodoc said...
Quote:
I'm a long term holder and extremely bullish on CTIX. I read the board daily but have never posted. The dosing discussion is interesting. Here's how I read it:
Cohort 8 dose is 215 mg/m2 (intravenous)
Mouse dose dramatically slowing tumor growth was 200 mg/kg (intraperitoneal)
Human Equivalent Dose in mg/kg= Animal dose (mg/kg) * Animal Km/ Human Km
HED Kevetrin= 200mg/kg * 3/37
= 17.43 mg/kg
Conversion of Cohort 8 dose from mg/m2 to mg/kg:
Cohort 8 Kevetrin= 215 mg/m2/37 = 5.81 mg/kg
So Cohort 8 Intravenous dose is 5.81 mg/kg. This dose is exactly 1/3 the INTRAPERITONEAL dose of 17.43 mg/kg used in the mouse study. Intraperitoneal dosing will result in lower serum levels than intravenous dosing. I do not know the correlation coefficient for Kevetrin IP/IV but it seems to me (if I understand this correctly) that Cohort 8 serum levels are likely in the same ballpark as serum levels obtained with 200mg intraperitoneal mouse dosing.
Best of luck.
I'm a long term holder and extremely bullish on CTIX. I read the board daily but have never posted. The dosing discussion is interesting. Here's how I read it:
Cohort 8 dose is 215 mg/m2 (intravenous)
Mouse dose dramatically slowing tumor growth was 200 mg/kg (intraperitoneal)
Human Equivalent Dose in mg/kg= Animal dose (mg/kg) * Animal Km/ Human Km
HED Kevetrin= 200mg/kg * 3/37
= 17.43 mg/kg
Conversion of Cohort 8 dose from mg/m2 to mg/kg:
Cohort 8 Kevetrin= 215 mg/m2/37 = 5.81 mg/kg
So Cohort 8 Intravenous dose is 5.81 mg/kg. This dose is exactly 1/3 the INTRAPERITONEAL dose of 17.43 mg/kg used in the mouse study. Intraperitoneal dosing will result in lower serum levels than intravenous dosing when comparing the same dose. I do not know the correlation coefficient for Kevetrin IP/IV but it seems to me (if I understand this correctly) that Cohort 8 serum levels are likely in the same ballpark as serum levels obtained with 200mg intraperitoneal mouse dosing.
Best of luck.
Quote:
So if scaling animal to human BSA is not a good model for estimating efficacy equivalence (but only for starting dose), what is a better model?
Empirical modeling. Isn't that what the Phase 1 helps to accomplish?
On a roll again. The Monsanto Zoetis connection..................Does it ever end with this OTC black sheep or soon to be NASDAQ Pharma darling? Waiting for Dr Menon to chime in.........
Thanks RJFL, I see the 200 mg/kg mouse doses on CTIX web site, and now looking back at the Kumar 2012 AACR poster, that in A549 lung carcinoma studies, 50 mg/kg Kevetrin was indistinguishable from controls, 100 mg/kg was better, 200 mg/kg better, and 2 cycles of 200 mg/kg best at delaying tumor growth.
I'm not really sure how to best scale these doses to humans, but scaling based on BSA seems like a good start. Of course the PK/PD differences between mice and humans matter greatly too. I'm sure the CTIX scientists have their models.
There was a nice point / counterpoint discussion of using BSA to dose cancer drugs (more for individual human dosage, not prediction of HED based on preclinical work):
http://www.nature.com/clpt/journal/v95/n4/abs...1412a.html
http://www.nature.com/clpt/journal/v95/n4/abs...0147a.html
"The historical rationale for using BSA-based dosing was to provide an allometric parameter for scaling dose determined in animals to humans, but that is not a sufficient argument to justify its use. Indeed, scaling has been used to determine the first level of dose of the first-in-human phase I study (usually 1/10 of the Lethal Dose 10)"
So if scaling animal to human BSA is not a good model for estimating efficacy equivalence (but only for starting dose), what is a better model?
I guess just use the animal data to estimate a safe starting point, then use the clinical trial data to determine efficacy and safety data? Maybe there are just too many variables for the simple BSA scaling to be useful, but I'd like to know what is a better general model.
Interesting idea about brilacidin for surgical prophylaxis. I work in the OR during many neurosurgical procedures, and IV antibiotics are usually given by the anesthesiologist / nurse anesthetist at the start of the case. I haven't seen powder form being used much. One of the orthopedic spine surgeons uses lots of antibiotic irrigation before closing, and has low infection rates, so maybe local wound application is a good idea in addition to systemic administration. While brilacidin resistance is less likely than for other antibiotics, I wonder if they will save the "good stuff" for the resistant cases? I would guess people would hold off on brilacidin use (just like they do now for daptomycin) for the vancomycin and methicillin resistant bacteria.
Etrade looking forward to it !!
Haha true that! Bush will def work, more of a Hobby guy myself!
Not sure if this was posted yet
http://seekingalpha.com/instablog/21116141-el...-will-blow
Hi KMBJN - Not sure if the question was directed at me but since I have been in this thread today in response to your question, the 200mg/kg mouse dosage amounts are what Cellceutix shows on their web page when it concern tumor response in lung, breast, colon and head and neck cancers, no dosage amounts are provided for the prostate and retinoblastoma studies. The questions arose from converting the mouse doses to HED by using the Baur BSA formula which is more correctly used for determining starting points for Phase I studies as opposed to direct conversions of dosages for human efficacy. I agree with "trusting Menon's expertise" and it is very evident many factors are involved in conversions. In additions these conversions are typically used for drugs that directly impact tumors by various mechanisms, so are they valid for a drug that restores P53, which in turn impacts tumors? With all the questions this process brought up I go back to the observed effects we have seen thus far, some patients having restaging/tumor arrest and multiple cycles/cohorts for multiple patients, thus a benefit was observed to those patient. That is important, (plus increased P21 expression in lymphocytes).
To end on an upbeat note tonight I wanted to pass along some interesting info regarding brilicidin. Recently Cellceutix said "B" is stable at room temp., I am not sure if that is in liquid or powder form. My daughter is a neurosurgical nurse and they routinely use Vancomyacin both in solution (mixed with saline by the nurse) and interestingly also in powder form within open incisions/surgical sites (mostly in back/neck surgeries I believe but perhaps other types of surgeries too) prophylactically. I wonder if "B" could also be used in this manner? Perhaps one of the posters who has a good history with correspondence with Leo (WildforCTIX) could pose the question if "B" can be used in powder form, just another potential use to consider.
Thanks for that!!
Good Morning, CTIX!
Great post thank you for sharing.
Have a great week everyone!
Oh yes it it! Flying in and out of there all the time. I'll take us to the party lol!
Calculations based on formulas in article cited earlier:
http://www.fasebj.org/content/22/3/659.full
I just plugged in numbers.
No doubt, intraperitoneal dosing likely has some very real advantages over IV administration, especially for intraabdominal tumors. Advantages include slower absorption and higher intraperitoneal drug levels. To achieve therapeutic serum levels to treat most tumors, I think modifying the intravenous protocol would be more controllable and preferable to intraperitoneal injection.
ROMAD Diver - You made me "snort" with laughter while eating a brownie, damned near choked but it was worth it!
I just found out from a secret source that found out in a meeting of secret people talking about secret stuff that they discovered Dr. Menon's secret ingredient used in Kevetrin. It ends up the secret ingredient is Chuck Norris DNA! Expect the news to come out sometime this week, and the share price to be somewhere in the $2,000,000,000 per share range.
DISCLAIMER! In order to relieve some of the tension on this board, this was meant as a joke. Do not trade based on this information--Chuck Norris DNA is unharvestable.
Thanks for the links KMBJN - it would appear from the abstracts they don't think BSA is the end all either and feel "alternatives based on fundamental principles of clinical pharmacology" are more appropriate. Lots of variables....... With regards to the vancomycin use, my daughter confirmed they use it a lot for back surgeries but not brain since there are concerns about ototoxicity. A study I read about vancomycin powder concluded "it doesn't cut infection post spine surgery as noted here:
http://www.empr.com/vancomycin-powder-doesnt-...le/324883/
But who am I to say....... maybe it makes the docs feel better that they are being "thorough".......
Do you have a source for that?
I found one thing ( http://www.medscape.com/viewarticle/780560) that seemed to indicate IP was superior to IV. I'm not exactly an expert so I don't know how this, if at all, would translate to our case.
Thanks for the insight that takes mouse dose administration verses human IV into account.
Hi biodoc, excellent observation! Never considered the serum level differences between intraperitoneal vs intravenous. Great first post, stop in more often.
I'll access the article below from my office tomorrow and see what McGonicle and Ruggeri (2014) have to say, but seems they advocate hierarchical data sets that may include Bayesian inference (Multi Treatment Comparisons) and Markov chain Monte Carlo. If anyone can access this, please feel free to do so and report.
Animal models of human disease: Challenges in enabling translation
http://www.sciencedirect.com/science/article/...5213004929
Looks like Dr. Menon's team is not using simple arithmetic modeling involved in Baur conversions except as a guide for starting dose, as noted by you and others.
I don't know if you are right, but your calculations, evaluation, and interpretation certainly make sense. Thank you for chiming in. I will look forward to seeing more of your posts in the future.
biodoc said...
Quote:
I'm a long term holder and extremely bullish on CTIX. I read the board daily but have never posted. The dosing discussion is interesting. Here's how I read it:
Cohort 8 dose is 215 mg/m2 (intravenous)
Mouse dose dramatically slowing tumor growth was 200 mg/kg (intraperitoneal)
Human Equivalent Dose in mg/kg= Animal dose (mg/kg) * Animal Km/ Human Km
HED Kevetrin= 200mg/kg * 3/37
= 17.43 mg/kg
Conversion of Cohort 8 dose from mg/m2 to mg/kg:
Cohort 8 Kevetrin= 215 mg/m2/37 = 5.81 mg/kg
So Cohort 8 Intravenous dose is 5.81 mg/kg. This dose is exactly 1/3 the INTRAPERITONEAL dose of 17.43 mg/kg used in the mouse study. Intraperitoneal dosing will result in lower serum levels than intravenous dosing. I do not know the correlation coefficient for Kevetrin IP/IV but it seems to me (if I understand this correctly) that Cohort 8 serum levels are likely in the same ballpark as serum levels obtained with 200mg intraperitoneal mouse dosing.
Best of luck.
I'm a long term holder and extremely bullish on CTIX. I read the board daily but have never posted. The dosing discussion is interesting. Here's how I read it:
Cohort 8 dose is 215 mg/m2 (intravenous)
Mouse dose dramatically slowing tumor growth was 200 mg/kg (intraperitoneal)
Human Equivalent Dose in mg/kg= Animal dose (mg/kg) * Animal Km/ Human Km
HED Kevetrin= 200mg/kg * 3/37
= 17.43 mg/kg
Conversion of Cohort 8 dose from mg/m2 to mg/kg:
Cohort 8 Kevetrin= 215 mg/m2/37 = 5.81 mg/kg
So Cohort 8 Intravenous dose is 5.81 mg/kg. This dose is exactly 1/3 the INTRAPERITONEAL dose of 17.43 mg/kg used in the mouse study. Intraperitoneal dosing will result in lower serum levels than intravenous dosing when comparing the same dose. I do not know the correlation coefficient for Kevetrin IP/IV but it seems to me (if I understand this correctly) that Cohort 8 serum levels are likely in the same ballpark as serum levels obtained with 200mg intraperitoneal mouse dosing.
Best of luck.
Quote:
So if scaling animal to human BSA is not a good model for estimating efficacy equivalence (but only for starting dose), what is a better model?
Empirical modeling. Isn't that what the Phase 1 helps to accomplish?
On a roll again. The Monsanto Zoetis connection..................Does it ever end with this OTC black sheep or soon to be NASDAQ Pharma darling? Waiting for Dr Menon to chime in.........
Thanks RJFL, I see the 200 mg/kg mouse doses on CTIX web site, and now looking back at the Kumar 2012 AACR poster, that in A549 lung carcinoma studies, 50 mg/kg Kevetrin was indistinguishable from controls, 100 mg/kg was better, 200 mg/kg better, and 2 cycles of 200 mg/kg best at delaying tumor growth.
I'm not really sure how to best scale these doses to humans, but scaling based on BSA seems like a good start. Of course the PK/PD differences between mice and humans matter greatly too. I'm sure the CTIX scientists have their models.
There was a nice point / counterpoint discussion of using BSA to dose cancer drugs (more for individual human dosage, not prediction of HED based on preclinical work):
http://www.nature.com/clpt/journal/v95/n4/abs...1412a.html
http://www.nature.com/clpt/journal/v95/n4/abs...0147a.html
"The historical rationale for using BSA-based dosing was to provide an allometric parameter for scaling dose determined in animals to humans, but that is not a sufficient argument to justify its use. Indeed, scaling has been used to determine the first level of dose of the first-in-human phase I study (usually 1/10 of the Lethal Dose 10)"
So if scaling animal to human BSA is not a good model for estimating efficacy equivalence (but only for starting dose), what is a better model?
I guess just use the animal data to estimate a safe starting point, then use the clinical trial data to determine efficacy and safety data? Maybe there are just too many variables for the simple BSA scaling to be useful, but I'd like to know what is a better general model.
Interesting idea about brilacidin for surgical prophylaxis. I work in the OR during many neurosurgical procedures, and IV antibiotics are usually given by the anesthesiologist / nurse anesthetist at the start of the case. I haven't seen powder form being used much. One of the orthopedic spine surgeons uses lots of antibiotic irrigation before closing, and has low infection rates, so maybe local wound application is a good idea in addition to systemic administration. While brilacidin resistance is less likely than for other antibiotics, I wonder if they will save the "good stuff" for the resistant cases? I would guess people would hold off on brilacidin use (just like they do now for daptomycin) for the vancomycin and methicillin resistant bacteria.
Etrade looking forward to it !!
Haha true that! Bush will def work, more of a Hobby guy myself!
Not sure if this was posted yet
http://seekingalpha.com/instablog/21116141-el...-will-blow
Hi KMBJN - Not sure if the question was directed at me but since I have been in this thread today in response to your question, the 200mg/kg mouse dosage amounts are what Cellceutix shows on their web page when it concern tumor response in lung, breast, colon and head and neck cancers, no dosage amounts are provided for the prostate and retinoblastoma studies. The questions arose from converting the mouse doses to HED by using the Baur BSA formula which is more correctly used for determining starting points for Phase I studies as opposed to direct conversions of dosages for human efficacy. I agree with "trusting Menon's expertise" and it is very evident many factors are involved in conversions. In additions these conversions are typically used for drugs that directly impact tumors by various mechanisms, so are they valid for a drug that restores P53, which in turn impacts tumors? With all the questions this process brought up I go back to the observed effects we have seen thus far, some patients having restaging/tumor arrest and multiple cycles/cohorts for multiple patients, thus a benefit was observed to those patient. That is important, (plus increased P21 expression in lymphocytes).
To end on an upbeat note tonight I wanted to pass along some interesting info regarding brilicidin. Recently Cellceutix said "B" is stable at room temp., I am not sure if that is in liquid or powder form. My daughter is a neurosurgical nurse and they routinely use Vancomyacin both in solution (mixed with saline by the nurse) and interestingly also in powder form within open incisions/surgical sites (mostly in back/neck surgeries I believe but perhaps other types of surgeries too) prophylactically. I wonder if "B" could also be used in this manner? Perhaps one of the posters who has a good history with correspondence with Leo (WildforCTIX) could pose the question if "B" can be used in powder form, just another potential use to consider.
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