Ann: Bisantrene with Decitabine Enhances Cancer Cell Killing, page-78

In my opinion:

Inqovi > IV Decitabine

It has clear bioavailability benefits that I believe will be essential to making this combination work effectively in solid tumors.

If peak Decitabine plasma concentrations are 500 nM, that doesn't mean intratumoral concentrations will be 500 nM - they are probably at a lower concentration. You therefore want to keep the concentration of Decitabine as high as possible for as long as possible. The benefit of Inqovi is that it has a longer half life, which means Decitabine peak is maintained for a longer time period ensuring greater delivery to tumors.

The benefit for Bisantrene is that it does not need a lot of Decitabine to synergistically kill solid tumor cells. The half-life for Bisantrene is 26-hours. A 200 mg/m2 dose will achieve peak plasma concentrations of roughly 3,000 nM. Because cardioprotection is not necessarily required, I suspect a smaller dose of Bisantrene may be used in patients.

I do not know what the dosing regimen might be, but I imagine a dosing regimen might be something like this, where a smaller dose of Bisantrene is used in combination with standard daily Inqovi dosing. This provides clinically relevant concentrations of each drug so that they may function effectively in solid tumors, while also preventing treatment related toxicities of each drug in combination. The 26-hour half-life of Bisantrene means roughly half the concentration of day one is added to day 2. Bisantrene dosed in the morning with Decitabine dosed later in the day will ensure Bisantrene is active while Decitabine concentrations are highest. A 1500 nM concentration has been shown to provide cardioprotection in multiple cell models, so this could very well be enough to decrease any cardiotoxicity. In fairness, dosing of each drug is going to be very complicated and I am just making an educated guess.