Testing, Testing 2 & 313 Dec 2023 23:24
The talk of preparations for the two week dosing regimen sparked a germ of realisation in me that I hadn't thought about previously, but which I think may explain why the next phase of the trial is so important.
I had (naively) thought that it was simply about navigating a course to finding the recommended dose for phase 2 as quickly as possible, within study parameters that would be likely to also give indications of even greater efficacy (because it is widely known that more frequent dosing leads to improved efficacy). However, I asked myself why more frequent dosing would be more efficacious and whether there might be more to it than simply being able to dose more chemo over the same timescale - and I think there is, much more to it.
Why? Because the third week in the current three week regimen must be the period when the patient is recovering the most from the toxicity of the dose they received two weeks earlier - it's effectively a week long detox period where the patient has the least Dox in them and they can build up their strength for the next round. But, of course, that must also mean that it's a period when the tumour will likely be growing, rather than shrinking. Put simply, it's literally two steps forward and then one step back.
Compare that with the two weekly dosing regimen, which is two steps forward and then two steps forward again, and again, and again. The compound effect of that on the relative mass of the tumour at the end of the 16 weeks must be huge, as it never gets a chance to grow, you just hit it again and again and again. In my simple analogy, after six three-week cycles, you would have taken twelve steps forward and six back (so six steps forward in total). With a two week cycle, you would take 16 or 18 steps forward and none back over the same timeframe.
Of course, in the real world, it's much more complicated than this, but the logic feels right - in fact, I suspect that the effects will be compound rather than simply additive, because it's all about % growth and shrinkage in tumour, so the first dose reduces the tumour size by x% and the second dose a further x% etc. Do the maths on that for two weeks of shrinkage followed by a week of growth versus continued shrinkage every two weeks (with no growth in between) and after 16 weeks the results are an order of magnitude apart. AND with AVA6000, you can keep going after the first 16 weeks for another 16 weeks, and then another and then another.
Does anyone know enough about the science to confirm or correct the above hypothesis?