Confusion, confusion and more confusion, that is how I would describe the current decision making process for a man with prostate cancer that has become newly castrate resistant. Just a few years ago the decision tree was clear, castrate resistant, immediately on to chemotherapy with docetaxel.
Today, in this treatment space, we have a number of new drugs available that are FDA approved. These include sipuleucel-T (Provenge) and abiraterone (Zytiga) with prednisone. Presumably in the next 3 to 4 months we will also have another new drug, enzalutamide (Xtandi) in this same treatment space.
Knowing which treatment to take, in what order and or in combination is the biggest question facing us when our prostate cancer becomes castrate resistant.
It’s commonly agreed by many physicians at the first treatment should be Provenge. Provenge has shown the ability to extend a man’s life, however it does not limit the rise of PSA or disease progression. Subset analysis of clinical trial data clearly demonstrates that the men who will receive the most benefit from Provenge are men with low PSA levels (most likely newly castrate resistant). It seems that the cut off for the efficacy of Provenge is around 22 ng/ml, so it makes sense to use Provenge first while the PSA level is underneath this threshold and the disease has not had major progression.
After the administration of Provenge the decisions become less clear. There has to be a decision between using Xtandi or Zytiga or perhaps both of these drugs in combination. Current knowledge from clinical trials does not provide an answer, so we need to fly by the seat of our pants.
Many would argue that it makes the most sense to first use Xtandi because Zytiga with a steroid comes with a list of side effects. After failure of Xtandi one could move on to Zytiga (with a steroid). However, to date there has not been any clinical trials that has demonstrated this order to be superior.
There is a small trial that has shown that in many cases Xtandi will still be effective after the failure of Zytiga. I am not aware of a trial with results that has shown the efficacy of Zytiga after Xtandi (not to say that it won’t be effective).
A little out of the ordinary, but something I find interesting would be entering into the clinical trial for ProstVac and then immediately having Provenge. Prostvac is the most promising new investigation immunotherapy on the horizon and I wonder what the one, two punch of Prostvac followed by Provenge could actually do to smack down advanced prostate cancer. (Caution- Prostvac is still in clinical trials and not FDA approved. Additionally, there are no trials looking at this combination of treatments, Provenge then Prostvac).
Becoming castrate resistance and not moving on immediately to chemotherapy can be frustrating. However the fact that we have these questions bodes well for us and it offers us serious hope for both today and tomorrow. Remember that just three or four years ago we had no choices. Having these choices without clear direction adds strain and anxiety, but it also offers options, new directions and an extended life with a decent quality.
There are currently a number of studies that are designed to give us better direction as to the best order of these treatments. Until then we must rely on the instincts and the experience of our doctors.
Joel T Nowak, M.A., M.S.W.