RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:The other two clinics Again my take is if patients are Sort1 negative the TH1902+docetaxel will not be delivered to cancer cells as the receptor isn't there then the body has to get ride of through metabolism and renal clearance etc so yes if not fully cleared it will be toxicity which theoretically will be in line with the dosage of the drug. Also there will be some off target delivery. They know the pharmacokinetics(absorption, distribution, metabolism and excretion) of docetaxel alone but not for their PDC which are important factors determining the toxicity.
It's not an absolute equation as they are recruiting patients with late stage cancers and those patients have over expression of Sort1 upto 60% note over expression is not zero expression so to answer your question they are many factors which could decide the amount of toxicity from off target delivery to pharmacokinetics of the drug and also amount of Sort1 expression for various cancers.
realitycheck4u wrote: Let me try this again as the point is being missed.
If a patients tumour has zero Sortilin, the TH1902 cannot really zero in on it, becuase thats what it does. It finds those receptors and then gets into the Tumor where the ph level being different allows the docetaxel to be releases and it therefore allows a greater concentration to be used in a human because it finds its ways to the right place before releasing this chemo drug.
So, my question is this. If the patient being tested (and who has not been tested for sortilin) has no Sortilin, what happens to the payload kin TH1902 of the docetaxol? Does it have a half live and just is no harm, or are you adding 3X or 4x of concentration of docetaxol into the blood, and it's dangerous?
scarlet1967 wrote: That's my take too since it will be some off target delivery and the PDC could fall apart in human blood before entering the cancer cells so there will be some side effects question is what are the range of those side effects compared to docetaxel alone.
Wino115 wrote: Depends on what you mean as dangerous since they are already using docetaxal as a chemo agent. If you see no response or limited response, it's not a suitable treatment for the patient. It won't be 100% repsonse, so this will happen a lot, and does already with chemo.
This is the scenario JFM has highlighted as to why it would be highly useful in the future to attach some kind of relatively harmless radionuclear marker to the PDC instead of the chemo and then image it so you can see if the tumor has massive overexpression and sortilin and where else the sortilin may be overexpressed in the body. Then you know the patient should response or not since it all depends on the overexpression of sortilin in the tumor cells. It's a great idea and I'm sure Marsolais is aware of it at this point and after they find out if there is actual efficacy, it would be interesting to see if they want to develop this kind of response test.
realitycheck4u wrote: Isn't this rather dangerous to do a trial where the patient has not been pre-screened for Sortilin then?? And if there is not sortilin to attract the PDC then what happens to the payload. Does it release anyhow