[Nguyen]

I am sorry, I am not being cleared in my questions. I understand the reasoning for blocking multiple pathways with multiple drugs, what I would like to know is more detail reasoning for selecting Xeloda (over others chemo) or Exemestane (over others AI) when combining either with “new” drugs. When reading lots of abstracts/papers, one reads lots of combinations involving these two vs others possible candidate. By “reasoning” I mean for example the “taxane” family inhibit microtubule where as Xeloda inhibits synthesis of thymidine monophosphate (ThMp), so maybe pre-clinical experiments showed that inhibit ThMp work better (than inhibiting microtubule) in combination with drug “XYZ”. Another possible “reasoning” might be Xeloda is perhaps cheaper or easier to administer due to it being in pill form. Another reasoning might be the “momentum factor”, since there are many Xeloda based combinations (hence lots of data), when testing new (particularly in combination) drug it’s “better” to use Xeloda as a based.

I’ve searched high/low (though not exhaustively yet) particularly for biological/chemical reasons of why these two (Xeloda and Exemestane) got selected over the others. My motive is to find hints for a possible combination with neratinib (possible next regiment for my wife) that is not Xeloda (already been used). Similarly hints for combination with Everolimus that is not exemestane. Hum, as I write this, maybe I can look at this in the reverse direction.

Thanks,

Nguyen