RE:RE:RE:RE:RE:Fireside Chat on August 10Christian 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"?