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Vorinostat or Romidepsin for Synovial Sarcoma?


#1

A new article from NCI suggests that HDAC inhibitors vorinostat and romidepsin could potentially benefit synovial sarcoma patients:

http://download.cell.com/cancer-cell/pdf/PIIS1535610812000839.pdf?intermediate=true

Yet only one clinical trial is recruiting sarcoma patients for vorinostat (in combination with another drug):

http://clinicaltrials.gov/ct2/show/NCT01294670

And other trials that started several years ago have presently an unknown status:

http://clinicaltrials.gov/ct2/show/NCT00918489

http://clinicaltrials.gov/ct2/show/NCT00112463

This is not the first time that HDAC is designated as a good target for synovial sarcoma and in the past, other HDAC inhibitors trials have been listed in the clinical trial database, yet all seem to end up in the "unknown status" eventually with no result, either bad or good. I am wondering what's going on behind the doors...


#2

The NCI article is referring to this study:

http://www.ncbi.nlm.nih.gov/pubmed/22439931


#3

Are you able to provide a copy of the article in the first link? When I click on it, it's a pay to view site...

Also, is anyone on any of these trials? Particularly the one using romidepsin? I'm trying to get any information of it working in synovial sarcoma... From what I've been able to read, it seems like these drugs could be very promising.


#4

The article must have been free at one point for me to put the link here. Unfortunately, I don't have it on my computer :-( May be, Mimi Olsson can get it. Ask her:

http://www.synovialsarcomasurvivors.org/profile/MiMiOlsson?xg_source=profiles_memberList

I haven't found one patient with synovial sarcoma who was able to participate in the trials. I have results of 2 vorinostat trials in children but no synovial sarcoma patients in those. I've known of 2 synovial sarcoma patients who tried to get into HDAC inhibitor trials and none were able to.


#5

One other question; I can't seem to find any information about a phase 1 trial for this one which is in phase 2: http://clinicaltrials.gov/ct2/show/NCT00112463

Does anyone have any ideas where I might find that?


#6

There were a few phase 1 trials for romidepsin. The drug has multiple names: FK228, FR901228, Istodax.

It's not clear what's the dose used in this phase 2 trial. But here are the results of a few phase 1 trials:

http://www.ncbi.nlm.nih.gov/pubmed/11895901

http://www.ncbi.nlm.nih.gov/pubmed/12440223

http://www.ncbi.nlm.nih.gov/pubmed/15466934

http://www.ncbi.nlm.nih.gov/pubmed/22536933


#7

Oh, thank you so much for that! I was really having a hard time locating any further information.


#8

Panobinostat, another HDAC inhibitor did not lead to positive results for the 6 synovial sarcoma patients in the phase 2 trial:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749588/