As new data becomes available it is important to revisit old...

As new data becomes available it is important to revisit old data to see the bigger picture.


Decitabine + Bis


Dox + Bis

Just reflecting on the prior preclinicals now trial is commencing. Dox+Bis shows a 2-fold improvement in 77% of cell lines. This could equate from anything between Dox+1% improvement to Dox+Bis (combined).

if we don’t know the Bis result alone then overall improvement is unknown. For example if Bis only produced a 1% killing effect the it would be Dox + 1% no that groundbreaking.

But we know Bis alone has been shown to be as effective as Dox as a single agent, in breast cancer.

What else does the data tell us?

14% has not improved in combo, but has it made the combo less effective than Dox as a single agent or just no improvement, data doesn’t tell us but Race would know.

Dox + Bis = Dox + Bis + synergy

In 9% the overall result is a greater killing than both drugs combined so an ‘extra synergy’. This suggests that Dox will sweep up cancer as well as normal + Bis will do the same (lack of cross resistance) and on top of that get a cancer killing boost.

Is 9% linked to anything per FTO that is creating this synergy? Who’s knows. But one theory is Bis kills cancer that Dox does not + let’s assume FTO reduces Dox resistance letter Dox work better.

How does this compare against Decitabine + Bis, this showed much great synergistic effect, 56% of the time. It could be partially explained by the fact Decitabine has a low base with solid tumours, but still leads to a synergistic effect.

What does it matter doesn’t sound that impressive?

Dox as a single agent can have a response of 15-20% and Dox + Paclitaxel 20%-30% so additive but not synergistic. But as a result cardiotoxicity 50% reduction in LVEF and 20% cardiac dysfunction.

A fair comparison would require Paclitaxel as a single agent v Bis single agent. But obviously the hope is cardiotoxicity is mitigate not increased in combo.

Now we are heading into trial perhaps all this is becoming irrelevant as we just sit back and chill whilst we wait for readouts. Enjoy!