Hello, my name is Susan Urba. I'm a medical oncologist, and I specialize in the treatment of esophageal cancer. I'm also a palliative care physician, and I specialize in pain and symptom management. I've prepared six modules from the oncologist point of view regarding the treatment of esophageal cancer. This particular module, we'll talk about the treatment of metastatic disease. The objectives, as we talk about this, are to establish goals of care for patients with metastatic esophageal cancer, to understand some of the palliative interventions we can do for dysphagia and poor nutritional status. To look at some of the palliative chemotherapy regimens, and to also look at targeted therapies, which are used more and more. So let's start with a pre-lecture question. What is the role of systemic therapy in the treatment of metastatic esophageal cancer? A, there is no role for chemo because it has no effect on survival. B, numerous targeted therapies are available and should be tried before turning to chemotherapy. C, chemotherapy reliably improves survival and should be tried in all patients with a good performance status. Or D, chemotherapy is most often used for palliation of symptoms. So let's start our talk by just doing an overview. First of all, when someone's diagnosed with metastatic disease, it's essential to talk about the goals of care, because this will guide the patient into what sorts of decisions they want to make. We want to do supportive care for symptom burden, trying to see if some of our interventions might help relieve symptoms. Some of the other palliative measures we can do are for dysphagia, which is probably the biggest complaint. We'll talk a little bit about stent placement or radiation, and also chemotherapy and targeted therapy. And most particularly, if at all possible, clinical trials. So the goals of care for metastatic disease is to tell the patient that treatment is really not curative. If patients know that, sometimes they elect no anti-cancer treatment because of possible side effects. Some of them say, if you can't cure me, and if you might make me sick with treatment, why should I take it at all? Others want to take their chances and see if they can get through treatment and possibly get some benefits. And all will require supportive care for symptoms management, whether or not they take chemotherapy. So what is symptom burden? Pain. And actually there are two modules in this Coursera course about pain in the thoracic oncology patient. Dysphagia and poor nutritional status. So talking about dysphagia, when patients can't swallow, one possibility of treatment is an esophageal stent. So if you look at the picture of the person there, you can see how the esophagus narrows where the tumor is. And it's not surprising that food gets caught there, and often the patient has to vomit it back up. So it is possible to have replacement of an esophageal stent. They come in different sizes and shapes and textures that they're made of, but this particular one, you can see all by itself and then in the esophagus, what it would look like. You could see how it just literally pops it open. I always tell patients it doesn't treat the cancer itself, it's literally pushing it aside so that food can go down easier. Some people, however, need feeding tubes, and there are two types of feeding tubes. One is called the Dobhoff feeding tube, which goes into the noes. That's a very quick, easy tube to put down. It can be done really in the office and then feedings are put right down through that tube. So even if they're not hungry, or if they have trouble swallowing, once that tube is down, the feedings go right the tube into the stomach area and helps give them nutrition. The other type of feeding tube is right into the stomach. It's called the G-tube or the gastric feeding tube. So a patient could be just sitting there. You'd never know it. Unless they lifted their shirt, and you could see the tube there. So for people who are going to have this for a longer period of time, we often do proceed to a G-tube. Sometimes patients get self-conscious about a tube coming out their nose, and it can be a little uncomfortable rubbing against the nose. But again, if it's temporary, such as if they're getting chemoradiation before surgery and really struggling with nutrition, sometimes the feeding tube through the nose is the best choice. From metastatic disease, often we got right to a G-tube. So now, let's about some of the chemotherapy agents. If you are an oncologist, you'd be very interested in all of this, I'm going to give you a quick overview. There are certain category of drugs, the platinum category, the fluoropyrimidine category. So as you can see, there's a good eight or nine drugs that are often given together or separately, usually not combining more than two, or maybe three maximum, together. Which chemotherapy to use with all these choices? Well, there have certainly been a number of randomized trials to help us decide. There was one trial, which is particularly relevant because it really was a good assessment of some newer agents versus older agents. The two older agents is just platinum, which has been around forever, as has 5-fluorouracil. Some newer variations within those families of drugs are oxaliplatin and capecitabine, which has the advantage of being a pill. And a lot of people just to soon take pill rather than coming in for IV infusions. So there was a big four-arm randomized study looking at various permutations of the old and the new drugs. And what did it find? Well, it was done with the statistics designed as non-inferiority. And the overall assessment was that there was no drug that was inferior to another, so you really could use any of them. But if you really look at the data, and you look at the one-year survival. On the far left, ECF which is the oldest group of drugs. That one, your survival is 38%. The newer set of drugs is 47%, so a little bit better. So that helps us pick which drugs we would use. So I think oxaliplatin is commonly used, capecitabine is commonly used. And again, just having a general idea of how these are compared and tested to each other is important, rather than memorizing the exact details about every single drug. So that's the standard chemotherapy nowadays, as we all know about personalized medicine or targeted therapy. So how is that important in the esophageal cancer? Right now, there are couple of approved drugs that are considered targeted therapy. In a former module, we did talked a little bit about Herceptin, which is an antibody geared towards the human epidermal growth factor receptor. And more recently, there has been a drug called ramucirumab, which has been approved, and this is also an antibody, and it targets what's called the VEGF receptor Inhibitor. Now, what's VEGF stand for? Vascular endothelial growth factor receptor. So this deals with the blood vessels that supply the tumor trying to interfere with blood supplied to the tumor to try and keep the tumor from growing. We've already talked in a previous module about this mechanism of action. Just to remind you, it's an antibody that keeps the EGF, the epidermal growth factor, from stimulating its receptor. And therefore, hopefully, to keep it from stimulating cell growth. This was looked at in a big trial, which they really screened 3,800 patients in tumors and found about 22% were positive for the Her-2. They randomized patients to get either chemotherapy plus placebo or chemotherapy plus this antibody every three weeks. And how did they do? Well, there was improved survival, so the drug was approved. But in all honesty, you really have to look at what was the magnitude of the difference. Median survival, if they got the trastuzumab, was 13.5 months versus 11.1 months. So granted it's a two-month improvement in survival, and that's important as we chip away at trying to improve survival. But these drugs are very costly, and in general, add small improvements to survival. Response rate was better, 47% versus 34%. That can sometimes be very helpful, because if we can shrink these tumors, particularly if they're causing dysphagia, we might be able to help the patients eat better without a stint, without a feeding tube. So in that regard, these patients could benefit clinically. The second antibody we talked about, the VEGF inhibitor. This just really shows how on the surface of the cells, there are the VEGF receptors, the vascular endothelial receptors. And if we give the antibody to block it, then hopefully, we're cutting down on the blood supply to the tumor. So there were randomized trials looking at this alone, just the drug itself. So it was placebo versus ramucirumab, and again, there was a statistically significant improvement in survival. But again, it was just approximately, and actually even less, than two-month improvement. However, when you think about it, as we identify each separate thing that may help improve survival, over time, we tend to try to combine these and see if we can get some additive improvement. It was also studied with taxel. Taxel plus placebo or taxel plus ramucirumab, and again, there was about a two-month difference in survival for those who got this antibody. So let's move now. We've talked about the chemotherapy, we've talked about targeted therapy. So in summary, let's go back to our post-lecture question. What's the role of systematic therapy for the treatment of a esophageal cancer? There's no role because chemo has no effect on survival. Numerous targeted therapies are available and should be tried first. Chemo reliably improves survival and should be tried in all patients. Or, chemo is mostly used for palliation of symptoms. And the answer is that it is really usually used for palliation of symptoms. Every now and then, we do see some improvements in survival, but we can't really say it reliably improves survival in all patients. Because as we saw, it's less than 50-50 chance that does patients even responding to the chemotherapy. And some who do get improvements in survival. But in general, if we can somehow shrink the tumor and improve symptoms, then we feel that we're doing something good for the patient. So the take home points in summary. Goals of care must be established so the patient can make reasonable quality of life decisions. We have to address dysphagia, weight loss, and pain, and we'll talk about pain in the next couple of modules. And chemo agents and targeted therapies afford palliation of symptoms. But sometimes, they can provide modest survival benefits. And therefore, some patients may benefit in many ways, but others hopefully at least so that they can feel better and have improved quality of life. Thank you very much for your attention.
