Why Capecitabine and Exemestane?

[Nguyen]

Hello,

Does anyone happen to know why Capecitabine/Xeloda is often chosen over many others chemo in combining with other drugs such as T-Dm1, CdK4/6, perjeta, TKIs, DS8201, Margetuximab, Syd985, etc.

Similarly, why Exemestane/Aromasin is chosen (over others AI) when combining with Everolimus/Affinitor?

Thanks for your thought,

Nguyen

[ariana]

No idea, I am on this along with NERLYNX . Of course I am turning 65 and medicare won't cover it. SO I AM WAITING FOR A CHANGE IN MY CHEMO PROGRAM...

Waiting for 2 weeks to hear and will be out of pills by mid Aug.

[Becky]

Affinitor is used in combination with Aromosin because in ER+/Her2 negative bc when Armidex or Femara has failed. It's the way the study was run and nothing more. Generally, the biochemical reaction in the body to inhibit the conversion androgens to estrogen is by inhibiting aromotase ( the catalyst for this reaction). Armidex and Femara use the same mechanism for this. Aromosin inhibits in a different mechanism.

I think your Xeloda question has a similar answer. Xeloda inhibits the synthesis of dna by inhibiting a chemical needed. It works differently than the other drugs mentioned and so the combo has a bigger punch by shutting down multiple mechanisms on reproduction.

[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

[donocco]

Exemestane (Aromasin) while being an Aromatase inhibitor like Arimidex has a steroid chemical structure like Estrogen. The other 2 dont and this may explain the different mechanism of action that Beckhy mentioned.

Cant say much about the Xeloda yet. This may help a bit. Xeloda is an oral prodrug of the usually IV given 5 flourouracil. Possibly the fact that it can be given orally is a factor. As far as insurance is concerned, price may be a factor. If this realy concerns you Nguyen Ill try to research it. Im busier retired now than I was working. Really in to increasing my astrology knowledge (plus learning something about all the new drugs) but if this really bothering you Ill see what I can find.


Paul

[donocco]

Nguyen

I called Novartis the makers of Affinitor. The reason they used Exemestane when the drug was first approved was that the clinical trials with Affinitor was
done on patients who were on Arimidex or Letrozole and progressed. This was
I believe was Bolero-2.

Now there is a Bolero-4 trial which did combine affinitor with Letrozole instead of Aromasin. The clinical oncologist at Novartis is going to e mail me it. From what he told me on the phone about the efficacy it may not be important which AI you use. He is going to E mail me both the Aromasin and Letrozole (with Affinitor) trials so I can visually compare the results. Ill let you know what I find.

Paul

[Nguyen]

Many thanks Paul, the Bolero-4 trial patients had Her2 Negative.

https://oncologypro.esmo.org/Oncolog...-Breast-Cancer

By the way, when you called Novatis, did you announce yourself as a pharmacist? I took many CME tests (and passed of course) specifically for bc, and can easily talk oncologist/researcher language, wonder if I should fake it to talk to these companies.

Thanks Paul.

[donocco]

Nguyen

I always tell them Im a pharmacist working with an online group.
You have a lot of knowledge and the pharmacist thing might make them more responsive.
I dont know if they can check the pharmacist thing by your name. Merck Sharpe
and Dome (Keytruda) asked me my address and they probably checked the State Pharmacy Board. Use your gut feelings. I always try to be honest but sometimes its relative. I cant say for sure but my guess is that the PAs and NPs who have prescribing powers dont know as much about the drugs as the pharmacists who dont. At least that has been my experience in retail, particularly with Tamoxifen. Calling the drug company saves a lot of time

Paul