August 4 2008 post: A blog reader (thank you!!!) sent me a bunch of interesting links, among which was one (see: http://tinyurl.com/5dc2us) about a marine-derived anti-tumour compound that annihilates myeloma cells in vitro and is extracted from a tunicate called Aplidium albicans.
According to Wikipedia, tunicates are underwater saclike filter feeders…weird-looking creatures that eat by filtering sea water through two openings in their bodies (“in” and “out” openings, sort of). They feed mainly on plankton. Not the prettiest creatures I have ever set my eyes on, that is for sure…ah, by the way, they are more familiarly known as sea squirts.
At any rate, this particular tunicate has yielded a substance called aplidin (drug name: plitidepsin) that is now being tested in Phase II clinical trials on relapsed or refractory myeloma patients, see: http://tinyurl.com/6rzumj.
An interesting thing about this compound is that it has a powerful in vitro activity against myeloma cells that have become resistant to conventional anti-myeloma drugs such as dexamethasone, thalidomide and bortezomib, according to the above-mentioned July 2008 study.
A June 2008 study (see: http://tinyurl.com/6k8l3w) tells us that treatment with aplidin was well tolerated by myelomic mice (sigh) whose serum paraprotein concentration was reduced by 42% and BM invasion with myeloma cells was decreased by 35%. Angiogenesis was also reduced to basal values. Not bad, eh!
Well, these two studies have been published only recently, and the clinical trial is ongoing, so we will have to be patient and wait to see what happens. Unfortunately, Sherlock wasn’t able to access the two corresponding journals, so I cannot even take a peek at the full studies. Oh well. However, according to the first abstract I cited (the July 2008 one co-authored by Dr. Ken Anderson), the preliminary trial results appear to be favourable.
I don’t have time to do much research today, but I did locate a 2007 study (full study: http://tinyurl.com/69mmhe) that informs us that aplidin has been given the “orphan drug” status for the treatment of acute lymphoblastic leukemia and multiple myeloma. This may speed things up…
Just as I was about to publish this post, I came across another interesting titbit, a review of aplidin on the IMF website (http://tinyurl.com/5dfplb), where you can watch a video presentation on aplidin by Dr. Enrique Ocio, University of Salamanca, Spain. Here we can also read that 31 relapsed/refractory patients were enrolled in the trial, median age 65: Out of the 26 evaluable patients, 2 (8%) achieved PR and 3 (12%) MR. Eight patients (31%) remained in stable disease (SD).
The conclusion was: Aplidin is effective both as a single agent and in combination with dexamethasone in the in vitro and in vivo settings. Its activity in relapsed/refractory MM patients is promising with an acceptable toxicity profile. There is quite a bit of interesting information on this page, so please have a look.