CTIX News 08/10/2014 12:20:47 $CTIX Yes, the assu
Post# of 64074
Posted On: 08/10/2014 1:20:54 PM
CTIX News 08/10/2014 12:20:47 $CTIX
Yes, the assumption that human equivalency in tumor growth delay is simply dependent on a 200 mg/kg dose shown in mouse studies, and using that number as the benchmark for expectations. That is not truthful.
Quote:
Kevetrin may be a good combination with chemotherapy and/or radiation.
The dosage in humans is no where near 200 mg/kg.
Stop the bullshit challenges. I'm only pointing out that using body weight, or even BSA, for converting to HED for other than starting dose is much more complicated than using Baur's simple formula. The misapplication of that simplistic conversion has caused much confusion over the years. The article I referenced points to exactly that problem.
I challenge you, since you are a seeker of truth, to enter a Ph.D. program and seek the truth regarding formulations for HED. It's a wide open field of study.
Please note that I am ignoring your insult "Now that you seem to be willing to logically and intelligently pursue the truth..."
Can anyone find anything untruthful in this post???
Do not expect miracles from Kevetrin
Limit your expectations for the Kevetrin Phase I trial to the realistic goal of finding a safe MTD that shows promise when used in combination with chemotherapy and/ or radiation.
For example, Avastin was not approved until it showed promise when used in combination with chemotherapy for colorectal cancer. Avastin has since made $BILLIONS in sales and is used as a treatment in combination with chemotherapy and/or radiation for a wide variety of cancers. Expect similar results for Kevetrin.
http://www.fda.gov/newsevents/newsroom/pressa...108252.htm
Kevetrin may be a good combination with chemotherapy and/or radiation.
The dosage in humans is no where near 200 mg/kg.
http://cellceutix.com/wp-content/uploads/pdfs...-11x17.pdf
http://cellceutix.com/wp-content/uploads/pdfs...0FINAL.pdf
Good luck and GOD bless,
George
BK
Now that you seem to be willing to logically and intelligently pursue the truth about the current 215 mg/sq m dose, then tell us based on the BSA method how does the 215 mg/sq m compare to the 200 mg/kg used in the animal studies???
I am interested in seeing the formulas and calculations that you will use for your comparison.
Good luck and GOD bless
George
As I said, the simple Baur's conversion is only useful for starting dose. There are a dozen recent papers on this mainly because there is such a disparity between preclinical and clinical results. While preclinical and clinical results align well, that alignment is on a curve that shifts upward or downward from species to species and from drug to drug. For HED conversion regarding extrapolations for other efficacy metrics, see bold below:
As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allometric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves the health and life span of mice. Immediately after the online publication of these papers, the scientific community and popular press voiced concerns regarding the relevance of the dose of resveratrol used by the authors. The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight, as was reported. For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.—Reagan-Shaw, S., Nihal, M., Ahmad, N. Dose translation from animal to human studies revisited.
http://www.fasebj.org/content/22/3/659.full
Please give it a rest , don't you have anything better to do on a Sunday ? Kick back and wait for some great news that is coming our way this week. go ctix and we will be seeing 2 dollars soon
BK:
Show me the direct quote from Dr. Menon!!!
Post a link to the quote!!!
Good luck and GOD bless,
George
RJFL:
Thank you again for your thoughtful, logical and intelligent response.
BK would have been correct if BK had said, "...that one of the uses of the referenced BSA formula is for determining "the selection of the maximum starting recommended starting dose in humans for Phase I trials..."
But BK did NOT post that.
BK posted, "...That conversion is only useful for establishing the starting safe dose for a Phase 1 trial...."
Notice the word "only". That word is very important.
Good luck and GOD bless,
George
It's a direct quote. This isn't Dr Menon's first rodeo.
To further cloud things, if you use Table one in the Sharma.... study you calculate HED by dividing the animal dose, in this case the mouse dose of 200 mg/kg, by 12.3, thus a result of 16.2 mg/kg is HED, conversely you can determine the HED by also multiplying by 0.081 which also yields 16.2 mg/kg. The conversions are based on using the exponent of 0.67 for body surface area in humans. I like the table 1 conversions better!
From reading the patent, it sounds like Brilacidin.
dgjared said...
Quote:
Check this out boys and girls. News on a malaria compound from the university on pen and cellceutix.
patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8,796,275.PN.&OS=PN/8,796,275&RS=PN/8,796,275
Going on 4 months now with this rounding saucer bottom projects initially to 1.90. And, if that is taken out, the pattern is valid and we can then start talking about measured moves. A 1x takes us to 2.40 near all time highs...................2x to 3.20, etc. Need a weekly close above 1.90 for starters!
Hi georgejjl. I believe BK is correct in his statement that one of the uses of referenced BSA formula is for determining "the selection of maximum recommended starting dose in humans for phase 1 trials" as that is one of the points mentioned in the study by Sharma and McNeill here:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737649/
That said, the earlier study I referenced used the Baur's Mouse model when extrapolating mouse to HED (human equivalent dose) does equivalencies and illustrated the common misunderstanding of such extrapolation by using the Resversatrol example they provided. I use used the formula since I was trying to determining the HED of the mouse dose of Kevetrin for the lung cancer study where it states "Mice were treated intraperitoneally with 200 mg/kg Kevetrin every other day for 3 doses. For comparison, another group of mice were treated with 22 mg/kg
paclitaxel IV every other day for 4 doses. In that study Cellceutix noted a 33% to 111% tumor growth delay compared to controls.
It would appear the current K study did use a variation of the BSA formula to determine the safe starting point. Using the NOAEL for Kevetrin which is 90 mg/kg in Rats, one I believe would calculate a "safe starting point in a Phase 1 study by the formula of 90 (the rat NOAEL)x 6 (the rat K factor) / 37 (human K factor, which yields about 14.6 mg/kg. I believe we started our Kevetrin study at 15 mg/kg so it would appear they used the Baur model to determine the safe starting point.
Again we have to defer to the expertise of Dr. Menon here and thus far I am pleased with what we have seen in the study. I can't fault anything BK stated and admit using the Baur model may not be correct application of the formula when coverting the mouse dosage of 200 mg/kg to HED so you can "expect" to see the same efficacy as was noted in the mice.......
imo the same as it was awhile back when we had all those chemists with russian names discussing the dosage along with polkadot.
i'm still with dr menon. no worries that way. ,especially when dr frei backs him up. 'nuff said.
gov
I, like probably most here, am totally ignorant when it comes to this topic and see no reason why anyone of us would not take Menon's estimate to heart. It's what he does.
I noticed that the half life of K varies from rat to dog to humans. Wouldn't that be one of many examples why results from straight conversions using mass (weight) or area would be skewed?
An interesting post from the past
Read this post carefully, then examine the FACTS and draw your own conclusions.
Yes, the assumption that human equivalency in tumor growth delay is simply dependent on a 200 mg/kg dose shown in mouse studies, and using that number as the benchmark for expectations. That is not truthful.
Quote:
Kevetrin may be a good combination with chemotherapy and/or radiation.
The dosage in humans is no where near 200 mg/kg.
Stop the bullshit challenges. I'm only pointing out that using body weight, or even BSA, for converting to HED for other than starting dose is much more complicated than using Baur's simple formula. The misapplication of that simplistic conversion has caused much confusion over the years. The article I referenced points to exactly that problem.
I challenge you, since you are a seeker of truth, to enter a Ph.D. program and seek the truth regarding formulations for HED. It's a wide open field of study.
Please note that I am ignoring your insult "Now that you seem to be willing to logically and intelligently pursue the truth..."
Can anyone find anything untruthful in this post???
Do not expect miracles from Kevetrin
Limit your expectations for the Kevetrin Phase I trial to the realistic goal of finding a safe MTD that shows promise when used in combination with chemotherapy and/ or radiation.
For example, Avastin was not approved until it showed promise when used in combination with chemotherapy for colorectal cancer. Avastin has since made $BILLIONS in sales and is used as a treatment in combination with chemotherapy and/or radiation for a wide variety of cancers. Expect similar results for Kevetrin.
http://www.fda.gov/newsevents/newsroom/pressa...108252.htm
Kevetrin may be a good combination with chemotherapy and/or radiation.
The dosage in humans is no where near 200 mg/kg.
http://cellceutix.com/wp-content/uploads/pdfs...-11x17.pdf
http://cellceutix.com/wp-content/uploads/pdfs...0FINAL.pdf
Good luck and GOD bless,
George
BK
Now that you seem to be willing to logically and intelligently pursue the truth about the current 215 mg/sq m dose, then tell us based on the BSA method how does the 215 mg/sq m compare to the 200 mg/kg used in the animal studies???
I am interested in seeing the formulas and calculations that you will use for your comparison.
Good luck and GOD bless
George
As I said, the simple Baur's conversion is only useful for starting dose. There are a dozen recent papers on this mainly because there is such a disparity between preclinical and clinical results. While preclinical and clinical results align well, that alignment is on a curve that shifts upward or downward from species to species and from drug to drug. For HED conversion regarding extrapolations for other efficacy metrics, see bold below:
As new drugs are developed, it is essential to appropriately translate the drug dosage from one animal species to another. A misunderstanding appears to exist regarding the appropriate method for allometric dose translations, especially when starting new animal or clinical studies. The need for education regarding appropriate translation is evident from the media response regarding some recent studies where authors have shown that resveratrol, a compound found in grapes and red wine, improves the health and life span of mice. Immediately after the online publication of these papers, the scientific community and popular press voiced concerns regarding the relevance of the dose of resveratrol used by the authors. The animal dose should not be extrapolated to a human equivalent dose (HED) by a simple conversion based on body weight, as was reported. For the more appropriate conversion of drug doses from animal studies to human studies, we suggest using the body surface area (BSA) normalization method. BSA correlates well across several mammalian species with several parameters of biology, including oxygen utilization, caloric expenditure, basal metabolism, blood volume, circulating plasma proteins, and renal function. We advocate the use of BSA as a factor when converting a dose for translation from animals to humans, especially for phase I and phase II clinical trials.—Reagan-Shaw, S., Nihal, M., Ahmad, N. Dose translation from animal to human studies revisited.
http://www.fasebj.org/content/22/3/659.full
Please give it a rest , don't you have anything better to do on a Sunday ? Kick back and wait for some great news that is coming our way this week. go ctix and we will be seeing 2 dollars soon
BK:
Show me the direct quote from Dr. Menon!!!
Post a link to the quote!!!
Good luck and GOD bless,
George
RJFL:
Thank you again for your thoughtful, logical and intelligent response.
BK would have been correct if BK had said, "...that one of the uses of the referenced BSA formula is for determining "the selection of the maximum starting recommended starting dose in humans for Phase I trials..."
But BK did NOT post that.
BK posted, "...That conversion is only useful for establishing the starting safe dose for a Phase 1 trial...."
Notice the word "only". That word is very important.
Good luck and GOD bless,
George
It's a direct quote. This isn't Dr Menon's first rodeo.
To further cloud things, if you use Table one in the Sharma.... study you calculate HED by dividing the animal dose, in this case the mouse dose of 200 mg/kg, by 12.3, thus a result of 16.2 mg/kg is HED, conversely you can determine the HED by also multiplying by 0.081 which also yields 16.2 mg/kg. The conversions are based on using the exponent of 0.67 for body surface area in humans. I like the table 1 conversions better!
From reading the patent, it sounds like Brilacidin.
dgjared said...
Quote:
Check this out boys and girls. News on a malaria compound from the university on pen and cellceutix.
patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8,796,275.PN.&OS=PN/8,796,275&RS=PN/8,796,275
Going on 4 months now with this rounding saucer bottom projects initially to 1.90. And, if that is taken out, the pattern is valid and we can then start talking about measured moves. A 1x takes us to 2.40 near all time highs...................2x to 3.20, etc. Need a weekly close above 1.90 for starters!
Hi georgejjl. I believe BK is correct in his statement that one of the uses of referenced BSA formula is for determining "the selection of maximum recommended starting dose in humans for phase 1 trials" as that is one of the points mentioned in the study by Sharma and McNeill here:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737649/
That said, the earlier study I referenced used the Baur's Mouse model when extrapolating mouse to HED (human equivalent dose) does equivalencies and illustrated the common misunderstanding of such extrapolation by using the Resversatrol example they provided. I use used the formula since I was trying to determining the HED of the mouse dose of Kevetrin for the lung cancer study where it states "Mice were treated intraperitoneally with 200 mg/kg Kevetrin every other day for 3 doses. For comparison, another group of mice were treated with 22 mg/kg
paclitaxel IV every other day for 4 doses. In that study Cellceutix noted a 33% to 111% tumor growth delay compared to controls.
It would appear the current K study did use a variation of the BSA formula to determine the safe starting point. Using the NOAEL for Kevetrin which is 90 mg/kg in Rats, one I believe would calculate a "safe starting point in a Phase 1 study by the formula of 90 (the rat NOAEL)x 6 (the rat K factor) / 37 (human K factor, which yields about 14.6 mg/kg. I believe we started our Kevetrin study at 15 mg/kg so it would appear they used the Baur model to determine the safe starting point.
Again we have to defer to the expertise of Dr. Menon here and thus far I am pleased with what we have seen in the study. I can't fault anything BK stated and admit using the Baur model may not be correct application of the formula when coverting the mouse dosage of 200 mg/kg to HED so you can "expect" to see the same efficacy as was noted in the mice.......
imo the same as it was awhile back when we had all those chemists with russian names discussing the dosage along with polkadot.
i'm still with dr menon. no worries that way. ,especially when dr frei backs him up. 'nuff said.
gov
I, like probably most here, am totally ignorant when it comes to this topic and see no reason why anyone of us would not take Menon's estimate to heart. It's what he does.
I noticed that the half life of K varies from rat to dog to humans. Wouldn't that be one of many examples why results from straight conversions using mass (weight) or area would be skewed?
An interesting post from the past
Read this post carefully, then examine the FACTS and draw your own conclusions.
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