I haven’t had a chance to review the data yet, but Danny Parker forwarded me these links moments ago:
Pat,
This just off the medical press and called out by Dr. Robert Orlowski.
Oral protease inhibitor, Nelfinavir, used against HIV, enhances the activity of Bortezomib against myeloma. Even more important, it appears to overcome resistance in myeloma cells to Bortezomib or Carfilzomib.
http://www.ncbi.nlm.nih.gov/pu
Full text:
http://www.nature.com/bcj/jour
Another article:
http://www.nature.com/cddis/jo
Clinical trials under way:
http://clinicaltrials.gov/show
http://clinicaltrials.gov/show
——————————————————————————————–
Thanks, Danny! See what you think everybody and please chime-in. Game changer or just another myeloma therapy “blip?”
Feel good and keep smiling! Pat
March 12th, 2013 at 12:20 pm
Pat,
As these results were in vitro (in the lab), I would qualify any enthusiasm until there is clinical data to substantiate. Still, the fact that the Swiss are moving ahead with trials is a good sign.
Also, Nelfinavir seems effective against pancreatic cancer as seen in these recent data from a Phase I clinical trial.
http://jco.ascopubs.org/content/26/16/2699.full.pdf
The phase I trial of nelfinavir with radiation, on 12 patients with inoperable pancreatic cancer, showed a doubling of survival times, and six patients had tumor regression to the extent that they became operable.
March 12th, 2013 at 12:49 pm
Game changer or blip? Hard to know but yet I think that sometimes what might be just a blip could be a game changer for an individual. I know there a participant on the list serve who received Epivir, another HIV drug to treat a hepatitis early in his MM care and he feels that made a difference with his myeloma response as well. Clinical trial of 1! As a nurse who worked in the HIV community, Nelfinavir was a pretty well tolerated drug. As I looked at the Swiss trials I saw that the Velcade is given IV. Isn’t reasonable now to expect that trials would allow the Velcade to be administered sub cutaneously. Who would want to risk the increased chance of PN?
March 12th, 2013 at 3:37 pm
Nelfinavir has lots of intolerable side effects.
“redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving protease inhibitors…
Gastrointestinal side effects of moderate or severe intensity have included diarrhea (up to 20%), nausea (up to 7%), and flatulence (up to 5%). Anorexia, dyspepsia, epigastric pain, gastrointestinal bleeding, mouth ulceration, pancreatitis, and vomiting
March 12th, 2013 at 3:58 pm
HI Danny,
) There also are fecal leakage issues not just “ordinary” u got 2 go diarrhea, but using diapers.
I agree with you about cautioning enthusiasm. These protease inhibitors used in HIV have a lot of untoward effects particularly metabolic disturbances, they can be as bad as steroids when it comes to lipodystrophy and that type of metabolic imbalance can lead to long term issues (I kno so can cancer
Now if you are refractory and need something that acts at another receptor site, you might elect this option. Neither bortezomib or carfilzomib act at the B2 receptor. I would like to see data on MM effects without those 2 agents. Particularly, since marzomib is in the pipeline and it acts at all the sites B1 and B5 like BTZ and CFZ plus the B2 receptor that nelfinavir has activity at. Nelfinavir appears to require a higher dose and to get strong activity and that can mean higher dose-limiting effects as mentioned above.
March 12th, 2013 at 7:57 pm
Great work, gang! Keep it up! Very helpful and informative…