Joe Tomaszewski, Ph.D.
Deputy Director, DCTD

Velcade, which was an agent that was brought to the NCI by Proscript, was a particular agent that required the use of a pharmacodynamic monitor to continue its development.

It involved inhibition of the proteasome and one particular one was the 20S isomer. And the analysis that could be done was simply after dosing either animals or patients, you took a blood sample and you could look in the white cells from that blood sample and see how much 20S inhibition was there.

So the 20Ss actually are very good or Velcade is a very good example of utilizing a PD assay to its fullest to guide dose escalation and it worked out extremely well. It was almost a textbook example of how a PD assay could be used to guide dose escalation and determine where your biologically effective dose is, as opposed to a maximum tolerated dose, which produces a lot of toxicity.