RE:RE:RE:RE:RE:RE:RE:Fireside Chat on August 10I am not a doctor, so I won't give any clinical advice. In my own case I ask questions to my doctors, but in the end I follow their advice, at least I did up to now, but since my diagnostic I was treated by compentent doctors offering me what I consider to be the best possible care at the time with what was available for my cancer at the stage it was at.
The only thing I would add concerning TH1902 and toxicity is that the 300 mg dose is only the equivalent of 1.3 times the maximum tolerable dose of free docetaxel injected alone. That's in good part why they did not see much toxicity at that dose, no matter the tumor burden or level of sortilin expression, or what I call "cancer sortilin burden", because the dose is just not that much higher than the MTD of free docetaxel alone. Also don't forget that ovarian cancer is one of the cancer type with the highest probability of sortilin overexpression. At the probability game, that's probably the reason why Dr Shah wants to try TH1902.
SPCEO1 wrote: Maybe you can be helpful regarding my cousin's situation. As a reminder, if she is reporting to me accurately, which is up for debate as she looks like she was just rescued from a Nazi concentration camp and seems to know little about her own cancer situation, she has stage 2 ovarian cancer with just one tumor. When asked about the tumor and why no surgery has been attempted, she does not seem to know. In any event, her CA-125 test was something like 130, so this seemingly indicates low tumor burden if I understand things correctly. If read what you are saying correctly, her risk of side effects is probably greater than the average patient. She is due to start the TH-1902 trial next week but has an important meeting with her regular oncologist tomorrow that may change her mind. From my perspective, which is admittedly not anywhere near educated enough, I wonder if TH-1902 is a good fit for her. Dr. Shah chose it over the immunotherapy drug he has had good success with, so I am sure he has good medical reasons for doing so. But if you have any thoughts that you think would be helpful to her as she considers all this and are willing to share them, I am all ears.
On a related note, if she does go forward with the TH-1902 trial, it is possible I will at some point come in contact with info that is material non-public info on TH-1902. I am guessing that chance is low until at least her six week scan and maybe beyond. Moreover, any updates I get from her would be anecdotal at best and would not be something I or anyone else should use to buy or sell the stock. But given the sensitivity of such matters, I will likely shut down my commentary here, either in regard to TH-1902 or maybe even totally, if I think I have anything that anyone might believe is material non-public info, even if I don't think it is. I will let you know if this becomes an issue but I suspect it will not until late September, if at all. And I do not know if she will join the trial in the end anyway yet though she seems to be keen to do so at the moment. Her oncologist might talk her out of it though and I am wondering myself if it is the best option for her situation.
jfm1330 wrote: Christian said on the CC that they did not see any neuropathy at 300 mg/m2 so far. But I will state once again that toxicity is related to tumor burden and sortilin expression level on tumors. If you have a small tumor, or tumors at the low end of the spectrum for what is called sortilin overexpression, or a combination of both, then there will be much more TH1902 available to enter other cells expressing sortilin, or for TH1902 to be degraded in the bloodstream and free docetaxel released. Just as a reminder, free docetaxel can enter any cell, including, obviously, healthy cells.
I gave the reference many time, but the fact that the percentage of the injected PDC ending up in the tumor is related to tumor burden and level of receptor expression is proven for Dotatate. Other factors are at play, in the case of Lu177-Dotatate the product is eliminated throug the kidneys, so the efficacy of the renal function is critical. In the case of TH1902, the elimination of docetaxel is through the liver, in the bile and the feces. So a patient with hepatic problems will eliminate docetaxel at a slower rate, hence, more toxicity elsewhere in the body.
So there are many factors that can play a role in toxicity. The dose Thera is giving is not adjusted for cancer sortilin burden (total tumor burden x sortilin expression level), it is adjusted for body size (surface area in m2). So they use a targeted drug without confirmation of the cancer related target presence and quantity. So there is no surprise in the fact that toxicity will vary from patient to patient. Remember, we have no confirmation that they have bipsies confirming sortilin overexpression. At this point this is the glaring hole in their scientific communication. It makes no sense to report on a targeted drug with no confirmation of the target presence on tumors or the amount sortilin on tumors.
SPCEO1 wrote: All good points to consider but what do you think about the patient who went for 33 weeks and only came off the trial because they wanted to return to "normal life"?