I'm sure there are currently huge amounts of thought being put into these kind of questions. My thoughts are as follows:
1) As Dr T. says, above, it's all about safety and cardioprotection. If they know the MoA of cardioprotection, we can assume they have a good idea of the dosing required to achieve it, and it's likely lower and/or shorter in duration than what is required for optimal anti-cancer activity. Since this is the first time that dox and bis have been dosed together, the safest bet is to start small. Imagine if Race went hard early with high/long/frequent dosing of bisantrene in this trial and failed to show either cardioprotection or anti-cancer activity due to some unforeseen toxicity.
2) There may be more sensitive measures of anti-cancer activity available to Race to monitor than just SD/PR/CR, which for example could potentially demonstrate a small/temporary reduction in cancer burden during the bisantrene dosing which reverses as bis is eliminated from the patient's system.
3) As the trial progresses and safety is demonstrated, perhaps that will allow increasing bisantrene dosing in both strength and frequency as part of dose escalation. We have yet to see the trial design.
4) The investigator-led AML trial may hopefully end up running more-or-less concurrently, and one would assume this trial will be dosing for maximum anti-cancer effectiveness. I'm not sure if this trial is also open label as there has been very little information regarding it forthcoming so far, but if so we could potentially be receiving preliminary data for both anti-cancer and cardioprotection in a similar time-frame.
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