Netterwald: Do you rely on specific guidelines to make decisions when building your regimens?
Crawford: The first thing in the NCCN guidelines is to use Sipuleucel-T, because this is a drug that is recommended to be used earlier in the disease process. Some of the drugs I mentioned still have not received the stamp of approval from the FDA, and the NCCN guidelines have not yet included these drugs. I think we will see oral drugs like abiraterone and MDV-3100 (when it gets approval) used earlier in these patients, delaying the use of chemotherapy for a while.
Netterwald: What clinical hallmarks do you choose to build regimens for your patients?
Crawford: There are certain seminal events that occur in prostate cancer. So we initially treat them with localized therapy. Some patients never have a problem, but some of them fail, and there is a rise in their PSA, which is the first event. We treat this group of patients with hormone therapy; this treatment is the next event. People do well on hormone therapy for a while. In some people, the cancer never recurs, and they get intermittent therapy.
However, some people fail in spite of hormone therapy, and there is an increase in their PSA level. At that point, they are castrate resistant, but they are not metastatic. Metastasis is the next step. And therapies are being used to delay metastasis. For example, denosumab has been shown to delay metastases by up to four months versus placebo. When people get metastases, it is another seminal event, and this is the space we are primarily discussing here. For metastatic patients, we would first consider Sipuleucel-T. The next drug that will receive FDA approval is abiraterone because of the positive studies. And then…when do we add radium 223 and MDV-3100 to our list of treatment options? When do we finally go to chemo?
The other trend I’ve noticed is that these patients are going to be in the hands of urologists. So I think the transfer of care to the medical oncologist is going to be delayed. I am not in favor of that. I think this should be a multidisciplinary approach. I think it’s important to have the three-legged stool, which consists of the urologist, the medical oncologist, and the radiation oncologist, all involved in the care of the patient. And it will be interesting to see how this plays out in the future.
Netterwald: Are there any hallmarks that you would rely on when making the decision to change or modify a regimen?
Crawford: We typically rely on PSA as the barometer of how things are going for a patient. We often say PSA stands for patient stimulated anxiety. And to some degree, physicians are anxious about the results of PSA measurement, too. So you might say PSA also stands for physician stimulated anxiety. So all bets are off once the patient has had episodes of failure because PSA is okay for screening, or for following patients, but it changes. However, PSA is still, fortunately and unfortunately, a marker that is still in use and one that will remain in use.
Netterwald: Docetaxel is the mainstay first-line therapy for this disease. Will that continue with all the emerging therapies?
Crawford: No, I think that will change with all of the new drugs that are being approved in this arena. I mentioned abiraterone, and there is also Sipuleucel-T. We will probably have MDV-3100 and radium 223. I think all of these new drugs will make a difference and will shuffle up the order and sequencing of regimens. That being said, we still use docetaxel to treat patients that are metastatic and castrate resistant as well as being moderately or minimally symptomatic.