Shubham Pant, MD: Now let’s go on to the next topic of treatment of carcinoid syndrome and treatment of neuroendocrine tumors. So, I’ll come to you, Dr. Morse. And you kind of talked about this before. How do you get the patients to manage the expectations? Like how do you say that this is how it’s going to be? It’s a long haul, how do you get them to manage the expectations? Talk about the side effects. Do you talk about them that this is what may happen?
Michael A. Morse, MD: We try to explain what types of therapies are out there, what the different options are for their particular cancer. For some people, the different therapies may be applicable to them at different points in the disease. And then, again, our emphasis is on using the therapies that are going to be effective but hopefully not cause undue toxicities or risks or side effects.
We always start with somatostatin analogs. They both control the symptoms and we know now that they control the rate of growth of these tumors as well. And for many people, that’s all they need for months or years. A time eventually comes when there is progression. If the disease is limited to the liver, for example, we’ll often use what are called locoregional therapies. Those are done by intervention radiologists, typically with catheters. They will go into an artery in the leg, direct the catheter up into an artery in the liver, and try to identify the blood supply to the tumor. They can deliver particles to block off the blood vessels so the tumor starves for blood. You can also inject particles that have chemotherapy embedded in them, and particles that have radioactivity—usually an element called Y-90—embedded in them. And for many people, those will also help the symptoms because they reduce the bulk of the tumor. In fact, you’ve had that done several times.
Larry Pleasant: I have. In fact, I had one just recently, about three weeks ago.
Michael A. Morse, MD: And the idea was to cut off the blood supply to certain areas of the tumor so the tumor there would die. And if it’s dead, it can’t produce serotonin so the symptoms can get better. And you’re obviously shrinking the tumor, at least controlling its growth, so there isn’t as much progression of disease. For people who have a tumor outside the liver or where those local regional therapies aren’t working or can’t be done for technical reasons, then we have other systemic therapies. The next one we typically go to is a drug called everolimus, or the trade name would be Afinitor. It’s an oral agent, it’s taken every day. My patients sometimes will ask, “Was that chemotherapy?” and technically, it’s not chemotherapy the way we think of chemotherapy that indiscriminately kills cells. But it is a targeted therapy. It interrupts a pathway that’s important in neuroendocrine tumors. And people, again, can take that for a period of time and have control over the growth of the tumor and sometimes some minor shrinkage as well. And if that’s no longer controlling the disease any more, that’s when we sometimes think about chemotherapy, or we go back to using the embolizations, the locoregional therapies, again. On the horizon, we’re very excited about the possibility that a radioactive drug given intravenously will become FDA approved in the next year. It’s called lutetium-177.
Shubham Pant, MD: Why do we have these complicated names for all these drugs when these diseases have complicated names?
Michael A. Morse, MD: I agree. But it’s a drug that has some similarities to octreotide. So, it binds to the receptors on the outside of neuroendocrine cells, but it is attached to a molecule that binds a radioactive drug called lutetium-177. When lutetium-177 undergoes its normal breakdown, it releases energy that can kill cancer cells, and this drug has been extensively used in Europe for a number of years. Indeed, I have some patients who travel there to get it. It was tested in a pivotal trial and is hopefully to be FDA approved in the next year, so it’ll be available for people who have had growth of the tumor after taking the somatostatin analogs.
Shubham Pant, MD: That’s great. So, exciting times ahead truly in this rare disease, that’s amazing to know. Tell me what somatostatin analogs, what are they? Are they a shot? Is it IV? Is it a pill?
Michael A. Morse, MD: The currently available forms of somatostatin analogs are given by injection. There are 2 that are given: one is given intramuscular, that’s octreotide long-acting, and then there’s one that’s given subcutaneously, that’s lanreotide. For people who have episodes of breakthrough where they need an extra dose, there’s a short-acting drug that can be given subcutaneously by the person themselves.
Shubham Pant, MD: Let’s say you have liver lesions. Is the goal to stabilize the disease, shrink the tumors? What is the goal, to decrease the symptoms of carcinoid syndrome, of these treatments that we talked about?
Michael A. Morse, MD: Some of these concepts of how to treat have evolved in just the past few years. Initially, it was really symptom management. If you could control the diarrhea and the flushing, people could live many years, even if the disease happened to progress. It was really the symptoms that were, in some cases, so debilitating or even lethal that we really needed to do something about that. When the somatostatin analogs came along and controlled the symptoms quite well initially, that allowed many people to live long enough where then the aspect of the tumor growth became more of a concern. Interestingly, along the way, it became clear that people were living longer if they were receiving these therapies. And that actually led to clinical trials to specifically answer that question, is there anticancer activity for somatostatin analogs? And now we know there is. So, fortunately, we can give a therapy that controls symptoms and also slows down the growth of the tumor. Shrinkage is not that common, but stability for a prolong period of time is.
Shubham Pant, MD: Now tell me about surgery. Larry had talked about, “I was not a surgical candidate.” Is it sometimes that people are surgical candidates? Does surgery have a role?
Michael A. Morse, MD: We always ask the surgical question. First of all, people often have their primary tumor in place. Amazingly, you can have a very small primary tumor that’s asymptomatic and have substantial metastatic disease in the liver. However, some people eventually do get symptoms from their primary tumor causing bowel obstruction. In those situations, people do need surgery. There are also people who only have the disease in the bowel. If it happens to be identified that early, of course we want to try to resect it as well. Over the years, try to deal with the liver metastases, or perhaps other metastatic sites of spread of the disease.
Shubham Pant, MD: You’re saying the way it’s being spread; liver, growth of tumor, which went from the small bowel to the liver.
Michael A. Morse, MD: Correct. Those tumors now, we feel that if we can remove 90 percent of the disease, we’re effectively setting the clock back. To get to the bulk of tumor that they have prior to surgery could take years. So, if we can achieve that, in some cases even 70 percent will be sufficient to suggest surgery is worth doing.
Shubham Pant, MD: And this probably would be in highly selected cases.
Michael A. Morse, MD: Absolutely. And we have multidisciplinary clinics. I sit right next to a liver surgeon, so every case, I discuss with him and ask those questions: Is it appropriate to do liver surgery in that particular individual?
Shubham Pant, MD: What is a multidisciplinary clinic, just so that our audience understands? This is a relatively new concept. Probably was not there a decade back? It has probably become more in the last decade.
Michael A. Morse, MD: One of the important things about a cancer like this is that it is managed by different specialists. The medical oncologist typically is the person who’s captain of the ship.
Shubham Pant, MD: Like a quarterback?
Michael A. Morse, MD: The quarterback, typically. But there’s a role for surgery in many people, like interventional radiology to treat lesions in the liver using catheter-based therapies. It’s uncommon to use radiation therapy, but there are scenarios where it’s useful. If somebody has a spread to the bone, for example, they might have it. And then there are a lot of other ancillary staff as well. Nutritionists, for example, patient supporters, oncologists and diverse practitioners, and the treatment room nurses. So, there are a lot of people involved in managing a case of somebody who has neuroendocrine tumor.
So, when we talk about multidisciplinary, we’re trying to bring in many different specialists to discuss a person’s case. Of course, it would be ideal if everybody can congregate and discuss that person right then. The reality is in large medical centers, we sometimes are in different places at different times. But we can still discuss the person. Either at a conference, a separate conference, or just by picking up the phone or by paging. But the nice thing is that I don’t have to wonder, is surgery going to be possible? I can just ask that question, and so I think it’s more important to think about the mindset of multidisciplinary and how you carry it out in your institution.
Shubham Pant, MD: So, Larry, does that make you feel special, having a whole team behind you?
Larry Pleasant: Well, actually it does. And it’s the reason that I would encourage anyone who’s faced with what I was faced with to seek treatment from a place like Duke. And this is not meant to be a commercial for you, but the point is to seek treatment where people deal with this all the time.
Shubham Pant, MD: Is it a rare tumor, the syndromes and everything?
Larry Pleasant: Because my experience has been, in the past 6 years, that many physicians knew about as much as I did about neuroendocrine tumors. I hate to say that, but it’s true.
Michael A. Morse, MD: Yes. And one thing I just want to just make sure we point out is, while it is important to get opinions at specialty centers that can bring in the multiple disciplines, we obviously work with peoples’ local physicians. There are many fine local oncologists who can see people on a regular basis while they’re getting their standards, somatostatin analogs or some of the other therapies, and then if there are decision points, that’s another time that we get involved. Some people do have the good fortune to be nearby and can see us on a regular basis, but for those who aren’t, it’s perfectly fine to have care locally as long as they know that from time to time it’s necessary…
Shubham Pant, MD: To come back to the mother ship.
Michael A. Morse, MD: To come back to a medical center that can help with the next step.