RE:RE:RE:RE:RE:Trial with unique way to deliver Docetaxel Glad you clarified this as I had confused therapeutic window with duration in all my posts. I thought it meant the likely time (months, years) you can keep treating patients with your dose and still keep the tumor at bay or shrinking. I was wrong as the window is the dose range possible with your treatment. Thanks for enlightening me and if anyone reads an old post of mine, I meant duration!
This comparison shows why a number of completely different research labs around the world gushed about Sortilin as a therapeutic target for advanced cancers over the last 5 years. THTX is clearly leading the pack and if it works, will own the space.
jfm1330 wrote: The therapeutic window, or therapeutic index is the interval between the lowest dose that will provide some efficacy and the maximum tolerable dose. In the cas of free docetaxel, this window, or interval is quite narrow, ranging from 60 mg/m2 to the MTD of 100 mg/m2. So the have some efficacy, you need to go close to the MTD, which is not good for the patient and limits the duration of the treatment because of cumulative toxicity after multiple cycles of treatment. The obvious advantage of a larger therapeutic window, is that it allows flexiblity in the regimens that can be used. As I wrote previously, with a large therapeutic window, you can decide to go for hammering the tumours with a dose close to the MTD that will come with a lot more toxicity, or you can decide to go with a lower dose, still having good efficacy, but much less toxicty, and that would allow for a longer term treatment, even, maybe, a sustained treatment, treating cancer a bit like a chronic disease, where you don't try to cure, but you simply try to prevent progression on the long term. So if TH1902 can show a MTD two to three times higher than free docetaxel, it would mean a large therapeutic window, on free docetaxel equivalent, it would mean 60 mg/m2 to 300 mg/m2, and maybe lower doses than 60 mg/m2 could show some efficacy because TH1902 would concentrat docetaxel in tumours, so maybe something like 30 mg/m2 to 300 mg/m2. That is ten fold between the limit of efficacy and the limit of toxicity. This allows for a lot of flexibility in regimen design and combo therapies.
SPCEO1 wrote: If THTX's therapeutic window is larger as seems likely, can you explain what that means for the success of TH-1902 from a commercial perspective? I think we can guess but I would rather get a clearer read on that from someone with your background.
Is there anything in the PK or PD info in that article that has any relevance for TH-1902? Hopefully, JFM1330 will weigh in on that as he clearly understands those aspects of it better than most of us.
Micelles are like small spheres that have structures similar to cell membranes that allow them to fuse with the membrane and deposit their content (docetaxel) into the cell. So better delivery of chemo to cell but the problem is it does this to all cells. Just looking at the abstract the results fit that. They can dose lower to get efficacy but seems like some DLTs also appear. It doesn't look like they've increased the therapeutic window size just shifted everything (efficacy and toxicity) to a lower dose. It might be more subtle than that and the toxicity profile might be better, I can't judge, but my first guess is the therapeutic window just moved, it didn't get bigger.
SPCEO1 wrote: My guess is there could be some interesting aspects to this paper for us and am looking forward to any comments JFM1330 and Qwerty might have about it. I could make some uneducated comments but that would likely be wasting everybody's time.
jeffm34 wrote: https://www.sciencedirect.com/science/article/pii/S0168365920303540
This was a phase I dose escalation trial as well. I assume Thera will be monitoring tumour size in each patient after every treatment cycle as well. Which means they should be seeing efficacy data all the way along the trial.
"The total tumour burden measured in this patient decreased from 129 mm at screening to 109 mm in cycle 2, 90 mm in cycle 4, 86 mm in cycle 6 and 85 mm at EOT."
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