Kidney Cancer: Serious Cases of Kidney Cancer
Guest: Dr. Harry Drabkin – Hematology-Oncology
Host: Dr. Linda Austin – Psychiatry
Dr. Linda Austin: I am Dr. Linda Austin. I am talking with Dr. Harry Drabkin who is an oncologist and Director of Hematology-Oncology here at the Medical University of South Carolina. Dr. Drabkin, let’s talk now about serious cases of kidney cancer, that is, when the cancer is large and, in particular, when it has spread to other organs. That is often when you get called in. How do you first diagnostically evaluate how serious it is? What are some of the tests you order?
Dr. Harry Drabkin: What usually shows up in people is evidence of spread of this disease. For example, a CT scan shows there are multiple lesions, for example, in the lungs. The lung is the site of metastatic disease, I would say, in about 80 percent of patients, so the lungs, the liver, the adrenal gland, the bones, something like that, that may be involved.
The cancers that I see, I see essentially all metastatic cancers involving the kidney. My surgical calling is, of course, to see the other side of this thing. So, we are looking at people that, for the most part, have a pretty sizable tumor in their kidney and have evidence of spread to some other organ site.
Dr. Linda Austin: The staging of cancer is something that may be mysterious for some people. Let’s just walk through it, what stages 1, 2, 3 and 4 mean.
Dr. Harry Drabkin: I think it can be a little simpler than that, okay. Like every organ system, we have sort of a size and grading system that helps in terms of things like prognosis. But, for people who have metastatic disease, it is either surgically removable when it is not metastatic and basically not, for the most part, a surgical disease when it is metastatic, with a really important exception. In kidney cancer, even with old treatments, taking out the primary tumor, if it can be done without a lot of complications, has been shown to be a beneficial thing. Plus, there is another important thing. Tumors can be big, they can hurt and they can bleed. Taking out this kidney tumor which can hurt and bleed makes life better for people. It is just like getting rid of a football size tumor, if you will. While that may not improve the overall survival, it sure can have a great impact on the quality of life.
Dr. Linda Austin: So, in other words, it sound like by the time these patients have come to you and they have multiple metastases, or multiple areas of spreading in the lungs, they are quite far along, typically?
Dr. Harry Drabkin: They are far along.
Dr. Linda Austin: So, systemic therapy, that equals chemotherapy?
Dr. Harry Drabkin: Well, until recently, until really the past couple of years, the treatment of this disease was just abysmal. We really had no drugs, with one or two exceptions, that had any activity. The exceptions were interferon, which had a low response rate, no complete responses, and somewhat minimal impact on overall survival, and an immunomodulatory drug called Interleukin-2 (IL-2) that for best responses was given in high doses, and is given in high doses. With occasional complete responses, it can be durable. The problem is that it is a very toxic therapy. So, overall, in unselected people, about six percent, seven percent, can have a complete response. But, for the most part, it was given in an intensive care sort of setting, the blood pressure support is critical, the blood vessels leak, people fill up with fluid, they develop fevers. And, in people, for example, that have underlying other diseases, like cardiac disease, whatever, it is not a safe treatment. So, it is a lot to go through for a relatively small gain, yet that small gain can be very real and extremely important. So, you try to choose that at an opportune time.
The kidney cancers, even before we knew a lot about the biology of kidney cancers, were always known to be very vascular. The tumor grows new blood vessels and it tends to stand out in that characteristic feature maybe more than other tumors. So, when some drugs came around that could block this angiogenic response, they were first tried in kidney cancer, and it turns out that, really, that is probably the sort of paradigm where these drugs have worked possibly even best.
Dr. Linda Austin: Let’s talk some more and let’s talk in more detail about how the vascular nature of these kidney cancers makes them more susceptible to treatment. By vascular, you mean they have a lot of blood vessels? The tumors are dependent upon all these blood vessels and little capillaries for growth and ,so, the treatment is targeted against factors that promote these little blood vessels to grow. Is that right?
Dr. Harry Drabkin: Exactly. It has been sort of a great concept in oncology. It came from some really pioneering work that Judith Folkman, at Harvard, did. What he demonstrated, for example, you could take a model system of a tumor, say you took tumor cells and you put them in a place where they could survive but they did not have access to a vascular system, for example, in the fluid of the eye, useful concept. So, the tumors set there, they grew to a few millimeters in size and they would not progress. If you put the same tumor cells in a place where they can have contact with the vessels, secrete factors that make these blood vessels come to them, if you will, then the tumors just continue to expand. So, they just cannot grow without new blood vessels. It turns out that kidney cancer, it really depends on this. It is inherent to this disease, more so, perhaps, than other tumors. Every tumor does this. But, there is an aspect about kidney cancer in which its biology seems to be driven in substantial part by some factors that have, as one of their targets, the ability to grow blood vessels.
Dr. Linda Austin: So, in other words, you inhibit the blood vessel growth, the tumor cannot grow?
Dr. Harry Drabkin: The tumor cannot grow. The tumor can shrink, the tumor can become partially nonviable, but it does not completely go away. But, it does stop growing. Now, the large majority of people, meaning, about 75 plus percent and maybe more as we start to cross drugs that have similar but somewhat different activities, benefit.
There are three new drugs that got approved in the past three years. One drug is called Sorafenib, it has a trade name, nexavar, another drug is called sunitinib with a trade name of sutent, and a drug called temsirolimus, or torisel, that have all come about. These three compounds work at least in part by blocking the blood vessel growth. Here is an important thing, a very important thing, to people. They block the blood vessel growth that is due to the factor we know most about, so-called VEGF, or vascular endothelial growth factor, VEGF. They can block that. What happens is, at some point the tumors become resistant to that therapy. It is not because the therapy does not work anymore. It is because, in large part, the tumor is making other factors that facilitate the blood vessel growth. We have selected for cells that are growing blood vessels by other mechanisms. That is where we are. There is a big challenge right now. We have gotten to, I always call it, we got to first base. You know, it is like for years and years, we did not get a hit. We got a hit and we are really on first base, and maybe second base. For the most part, most or all, patients at some point will progress with these therapies. We have done a lot to improve the quality of life. We have extended survival but we are not at the cure stage and that is our goal. We have to push it now to make more second base and third base hits, and occasional homeruns. That is the goal.
Dr. Linda Austin: With these new angiogenesis inhibitor drugs, the drugs that block the blood supply from growing, how has that improved rate of survival? Can you put numbers on that?
Dr. Harry Drabkin: Well, the easy numbers are, you know, roughly, we are probably doubling rates of survival for many patients. Some patients, we started these trials before I came, while I was at the University of Colorado, it is probably going on three years and we still have a group of people that their disease has been largely dormant on these agents and are still continuing to do fine.
Dr. Linda Austin: For three years?
Dr. Harry Drabkin. For three years. It is a minority, okay. We have seen probably more like gaining six months period of time, or whatever, people progressing after a year or two years, and a small group of people that do not respond at all. So, that is an important challenge, to identify what is going on in the tumors that do not respond and, also, how we make the next step after there has been progression of the disease. That is why the clinical trials are so urgent in this.
We have new drugs and we have a lot of combinations to test and a lot of work to do. It is great that these drugs are out there, that everybody can get them. But, I think, the most challenging aspect now is to go after the next generation of drugs, the next generation of combinations and keep pushing this disease until, in a way, the analogy, again, that I like, is like AIDS. We are not getting rid of the virus. But, with enough effective therapies, we are keeping it under control to the extent of having relatively normal lives and living with this potentially deadly virus that can escape.
Dr. Linda Austin: Dr. Drabkin, in another podcast, I want to talk to you about some of the clinical trials that you, personally, are involved with here at the medical university. Thank you very much.
Dr. Harry Drabkin: Sure.
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