Kidney Cancer: New Research and Clinical Trials
Guest: Dr. Harry Drabkin – Hematology-Oncology
Host: Dr. Linda Austin – Psychiatry
Dr. Linda Austin: I am Dr. Linda Austin. I am interviewing Dr. Harry Drabkin who is an oncologist and Chief of Clinical Hematology-Oncology here at the Medical University of South Carolina, a nationally known expert in the area of kidney cancer. Dr. Drabkin, let’s talk, in this podcast, about some of the new research that you are involved in here at MUSC in this area.
Dr. Harry Drabkin: We have made a lot of progress in kidney cancer, a lot of progress compared to what the disease was like before a couple of years ago. The analogy I use is, for the most part, most people are getting to first base or even second base and a little beyond. We need, now, to identify which factors, which blood vessel growth factors, are most responsible when people stop responding to the current drugs. There are two strategies, one, new drugs and two, combinations of existing drugs. So, basically, all that is ongoing.
Clinical trials, for the most part, come and go. Most of the new agents, or all of the new agents, are coming from the pharmaceutical industry because that is where new drugs largely come from. They may spring from basic research that is done and supported by the National Institutes of Health and done in academic centers but to take a drug to market is a lot of work, years of work, and a lot of investment. So, the strategy is basically to take new promising agents that have gone through Phase 1 studies, have been proven to be safe and show suggestions of activity in specific diseases and test those further. So, the strategy, again, is to enroll patients quickly in multiple centers, often, within the country as well as in centers outside the country to answer questions most rapidly and then move on in terms of what is next. That is why I say that trials tend to come and go. They are always somewhat of a moving target.
What are the existing trials that we have right now in kidney cancer that are new? Let me give you a couple of them, and there are multiple ones planned. We can talk sometime about how a new combination gets to a trial. For example, we have a combination of one of the standard drugs, standard, meaning, in the last couple of years, sutent, combined with an antibody against VEGF called avastin. So, we are blocking not only the growth factor VEGF with the antibody but we are blocking its receptor with this drug sutent. The idea is, will the combination be safe? It looks like it is safe. Will it be more efficacious than either one alone? The goal is always yes. But, these are biologic and clinical science questions and you do not know the answer. If we knew the answer, we would not do the trial. That is one trial.
The second trial that is ongoing right now is a second drug called Sorafenib/nexavar. It is being combined with a molecule from Amgen called AMG 386 which is a designer sort of drug that targets another growth factor called Angiopoietin-2, made by kidney cancers, has clear angiogenic activity. It looks very safe when combined. The question is, is it more efficacious than the Sorafenib alone?
The third trial that is ongoing right now is a recombinant molecule called IL-21 that stimulates a subset of lymphoid cells. Kidney cancer has been one of the diseases that for a long time has had some degree of response to modulating the immune system. IL-21 is now being combined with Sorafenib to ask the question, is it better than Sorafenib alone?
Several years ago, a group at the NCI demonstrated that you could take lymphocytes, or white blood cells, from people with cancer, expand them, if you will, in a test tube and give them back to people, and the question was, would those cells go after and attack the cancers and do something good? Out of that work, which was ongoing when, I think, I, probably, started my fellowship in 1980, demonstrated that kidney cancer and melanoma were the two diseases that showed these kinds of responses, not in the great majority and somewhat of a minority of people, but sometimes responses can be dramatic. The offshoot was, for example, today we have this compound, Interleukin-2 (IL-2), that has about a six to seven percent complete response rate of which they can be long lasting if not tantamount to cure. The problem is it is a toxic drug and only benefits a minority of people.
So, when these immune sorts of studies were expanded, it was found that the results with the Interleukin-2, this sort of stimulatory molecule to these lymphocytes, was just as good as the cells themselves and a lot less work, a lot less cumbersome to do. So, that is where this sort of concept has come from, that kidney cancer and melanomas can respond to modulating the immune system. I must say that the immune system is still a very complex set of cells and signaling devices. It is still being worked out. They have vaccine approaches and the drugs that modulate that approach are still being worked on. All I see is progress. I am not an immunologist but when I listen to the immunology talks, I actually get excited. I think we are getting close. I think we are getting very close.
Dr. Linda Austin: Now, for a patient, or a family member, who is interested in learning more about these clinical trials, who should they call? What should they do?
Dr. Harry Drabkin: For people with kidney cancer, I am more than happy to see people in clinic to provide second opinions, to help with managing their care, to act as a consultant, to act as the primary physician, whatever, and our group is delighted to do that.
Dr. Linda Austin: So, they could call our central MUSC number and be referred to you for an opinion?
Dr. Harry Drabkin: Absolutely.
Dr. Linda Austin: Dr. Drabkin, I wish you all kinds of good luck on this exciting work you are doing here. It is so important.
Dr. Harry Drabkin: This has been a very stimulating area for me. I got into this particular work because my lab had, for a long time, gone after a particular chromosomal rearrangement that caused a form of hereditary kidney cancer and when we finally isolated the gene and started to figure out how it worked, it was clear that that was going to be a mainstream sort of pathway. Before, my clinical interest had been leukemia. I find kidney cancer fascinating, maybe even more fascinating than the leukemias, because we know so much about it now and there are so many biologic areas to go after. I am always reminded, everyday, I think, by the people that I have seen who have done well and, just as well, by the people who do not do well. I am pushed by those people and, knowing them, we have got to make more improvements in this disease. It is a passion.
Dr. Linda Austin: I can see that. Thanks for your work.
Dr. Harry Drabkin: Yeah, you bet.
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