RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:RE:FittingOne of the science experts here should answer this but I will take a stab anyway:
1.) The MTD will be determined by stepping back one dosage level from the dosage that leads to two or more patients showing signs of toxicity. So, you can have one patient outof an eventual 6 who has a bad reaction to a dose and still make that your MTD. Clearly, TH is looking to be able to pump as much Docetaxel into a patient as possible as that should improve the efficacy but there is likely more to this equation than is readily apparent. The MTD might not be the dosage they end up using in the rest of the trials as they seek the best overall solution. For example, they could use the MTD early on to weaken the tumor and then fall back to lessor doses to extend the time the patient can be treated.
2.) I am not sure specifically, but I imagine toxicity is defined by any number of measures. The patient gets physically sick or their bloodwork shows any number of potential complications. I don't imagine that it is hard at all for TH to determine toxicity.
3.) In terms of this study, I imagine the toxicity has to show up in the first three week cycle to be initally relevant. But, if it does not show up in the first cycle, then the patients move onto to higher doses in a new cycle and toxicity can show up in those following cycles too. I don't think this drug lingers in the body much so I am not sure that time is as big a factor as dosage level.
4.) Just guessing but if you stop taking Docetaxel as a normal cancer patient, you get better (at least in terms of side effects). I imagine that happens relatively quickly as it does not seem the drug accumulates in the body.
Those are my best guesses and they should be treated as guesses from a non-medically trained person giving it his best shot. Hopefully, someone who knows a lot more about this will make the appropriate corrections to what I have said.
palinc2000 wrote: At what point do they determine that MTD has been reached,,,How is toxicity defined? Is there a time factor involved,,,?Can toxicity be reversed after a a few days .....?