Well-tolerated in drug testing can mean a whole ra

Well-tolerated in drug testing can mean a whole range of possibilities. It's one of those imprecise wiggle words for which FDA reviewers have a distaste. It can range from only minor occasional reactions like rashes, nausea and minor dizziness to much more severe reactions. In oncology it often means that the drug doesn't kill people at therapeutic levels, but hair falls out, tere's vomit (a lot), complete loss of appetite, severe dizziness and disorientation, high fever, swelling and bloating, or any number of problems just short of death.

When I say well-tolerated, to give it a more precise definition, I mean minor occurrences of all those things and at the MTD which is the standard for most other drugs outside oncology. In animal studies, the more Kevetrin that was administered, the more effective it was and  by the most critical measure: tumor arrest and reduction. The MTD was well above the high efficacy threshold, and the animals experienced only minor and occasional vomiting, disorientation, fever, loss of appetite. Moreover, LD50 for Kevetrin, the lethal dose where 50% of all animals die, was significantly above the MTD.

So, when I say I expect no different outcome in humans, I mean the onset of MTD symptoms will not yet appear at highly effective levels. Moreover, there should be no expectation of any adverse or toxic reactions for at least 2 more dose increases. The 4th cohort may begin to show dose limiting symptoms, but efficacy should be well-established by the end of the 3rd round.

I want to make clear that this is all my opinion, but does come from data in published and public animal studies.