QUESTION: My understanding has always been that serum C level remain elevated, ideally between 350 and 450 ng/dl for several hours. What I have found is that the mid treatment results of serum C as determined by the Tru-2-go glucometer (one hour into treatment after half of the solution has been infused) generally gets within range. However, the post treatment reading often drops by 50 to 150 point, dropping the value to well below the desired range. This has been the case even when I use doses up to 80g of AA. How is it possible to maintain serum levels at a therapeutic dose for long enough to be cytotoxic to cancer cells?
ANSWER:
1. I have not done the “1/2 the IV in 1 hour and the rest over a longer time” procedure for many years. Reason being that it doesn’t make much difference from a pharmacologic point of view, and definitely has not affected outcomes since discontinuing it in 2006-7. (Or earlier). I think we stopped saying it was the way to go in advanced IV classes around 2010 but it could still be in some notes.
2. When I did do that if checking the Serum ASC then often the serum ASC is at a peak at 1 hour. Again since stopping that procedure I don’t check in the middle of the IV.
3. I don’t really think it states anywhere that serum levels remain at the direct post IVC level for “hours”. I have never seen this, but they will remain elevated for up to 6-8 hours post (although following Zero Order kinetics (as IV ASC does) the drop faster the further away from the end of the IV – as opposed to logarithmically as in First Order drugs). They will throw off a glucometer for 4-8 hours but never at the higher levels. If it does state that in a document it is incorrect.
4. In the last 8-10 years we run the IV at a steady rate of no faster than 0.5 grams per minute. In most this is sufficient, and as mentioned above is as or more efficacious than the old “1/2 fast then slower” method.
5. Using this steady rate we normally see levels of 350-450 post IV. The dose required runs from 37.5 to 150 grams – across an “almost” Bell curve distribution. The median is 50-100 grams.
6. Another confounding variable is that if one tests after each IV what dose got a patient to 400 one IV may only get them to 150 the next week. Then it may go back to 400 or only 250 then 450 the following IV. This is because the totally unpredictable variable of cellular uptake makes the serum retain a lot of ASC on one occasion and less (because it entered the cell faster that day) on the next. This is a very real phenomenon based on many variables on the day of the IV.
7. Finally the real question is “does it matter?” Some will say yes and some no. The idea of cytotoxicity with HDIVC is quite variable and really only a small part of the likely plethora of MOA’s anyway. Based on all the data we collected running at steady state I’d say that the best practice (which relates to our positive outcomes) if trying for “high dose” protocol is:
- Base the Rx dose on the post IV ASC in the beginning and go for 400 +/- as you are
- Run the ASC at a steady rate of 0.5 grams / min or slower
- Use the 2010 formulas I published based on the BIORC work
- Re-evaluate after 15-20 HDIVC to see if the approach even is worth doing (about 50% is our experience benefit in a way one can assess).
- Know that there are many reasons a low dose IVC approach may help non responders in a totally non plasma level based manner.
- Also if HDIVC isn’t working an adjunct (like Artesunate) may help.
- If HDIVC isn’t helping by 20 IV’s switch to another therapy, or at least consider that.