An Exclusive Interview with E. David Crawford, MD
Professor of Surgery/Urology/Radiation Oncology
Head Urologic Oncology
E. David Crawford Endowed Chair in Urologic Oncology
University of Colorado, Denver; Aurora, CO
Dr. E. David Crawford, an internationally renowned expert in the treatment of metastatic castrate resistant prostate cancer, offers his predictions about emerging treatment options and how they will fit into the current regimens.
James Netterwald, Staff Writer: Has metastatic castrate resistant prostate cancer (MCRPC) been a hotbed of pharmaceutical development over the last decade?
Crawford: I’m not sure I would say that it has been a hotbed of development over the last decade. I would say that a lot of the great studies have come to fruition in the last year or so. And these have resulted in the approval of four new drugs. There are also two or three more on the way. The last year and a half has created a lot of excitement for this therapeutic area. Prior to that, it had been trial and error when it came to building chemotherapeutic regimens. Now we have drugs that are unique. They are not just chemotherapy but have diverse mechanisms of action. There should be synergism in a therapeutic regimen. And a lot of excitement exists because now we can begin to talk about sequencing these new drugs, and also about really slowing down this disease process, with the hope that we could convert this into a chronic disease.
We have some parallels with other cancers where monotherapy has been okay, but it has not made a big impact. So now we have arrived at a point where we can think about putting bone-protective agents together with agents that affect testosterone chemotherapy and radiopharmaceuticals, so that we will be able to see a really big difference in slowing the disease process. It’s an exciting time that has really just sprung forward in the last year and a half.
Netterwald: How do you build your patient regimens with the many different types of drugs available?
Crawford: First of all, let us pretend that we live in an ideal world where we are not worried about cost or FDA indications or approval. The bottom line is that we are going to see a shift in the use of chemotherapy. However, when building a regimen from the current therapeutic options, I think we are going to start out with a therapy that affects the immune system, namely Sipuleucel-T, which is indicated for metastatic, castrate resistant prostate cancer that is relatively asymptomatic. This drug is well tolerated and has a significant impact on survival rates. The difference is even more striking in certain subsets of patients. That is a foundation for building a regimen.
It used to be that you would wait until the patient had symptoms, then became resistant to hormone therapy before starting chemotherapy. But I think we’re going to see greater use of androgen biosynthesis inhibitors such as abiraterone. We are also going to see greater use of drugs such as MDV-3100, which has a different effect than abiraterone. I think we are going to see these two drugs utilized together.
For the bone issues, we have the RANK ligand inhibitors which will play a role from the beginning of hormone therapy to prevent osteoporosis, to delay skeletal-related events, and to delay metastasis. Also, another bone agent is called radium-223, which will be used earlier in this disease process. I think what we will see that chemotherapy is being delayed because there is a rationale for using these newer agents earlier than usual. We may be alternating the use of chemotherapy with the use of non-chemotherapeutic agents. There’s an endless number of possibilities, which is a better position than where we were a year and a half ago when we only had chemotherapy. Then the argument was when to start chemo and how long to use it.