Choosing the Best Therapy for Neuroendocrine Tumors
Robert Ramirez, DO, FACP: Treatment options vary. The first thing I think about is surgery. Now, I’m a medical oncologist, so I give chemotherapy and targeted therapy all the time. I also work with some very, very good surgeons who are very technically skilled but who are also very smart and know when not to operate on patients. It is very important for me as a medical oncologist to be part of that team. If they think that a patient is a candidate for surgery, then we discuss this with the patient and see which approach we want to take. Unlike some of the other higher-grade malignancies or some of the more traditional-type cancers that you would see such as lung and breast—where someone has disease that has spread from the original site so they say, “Well, surgery is not an option”—in this disease, we can actually perform surgery to debulk or cytoreduce this patient. We essentially take out anything that we can see and can safely take out. We have noted that this does improve symptoms, quality of life, and survival. We get very long-term survivors who come in with stage 4 disease, we operate on them, and they have very good outcomes. That is always the first thing in my mind: Can this patient be operated on?
Many times, the disease is confined to the liver and pancreas. Sometimes we say, “Well, if that is it and there’s no disease elsewhere, what about transplant?” We’ll talk about that later on. This may potentially be an option for certain patients with neuroendocrine disease. If the majority of the disease is confined to the liver and patients are symptomatic, we think about liver-directed therapy. Now, there are different ways to deliver liver-directed therapy. We talk about something called chemoembolization. We talk about bland embolization or radioembolization. These things work for taking care of those tumors that are in the liver, and they tend to work very well. Now, which one of those 3 types of embolizations is best? At this point, we don’t really know. There is actually a clinical trial we’re involved in that’s run by Mike Soulen out of the University of Pennsylvania, who is the national PI [principal investigator] on this, that’s trying to answer this question of which form of radioembolization is best for patients with neuroendocrine tumors. Hopefully, we’ll have the answer to that in the coming years.
Beyond surgery and liver-directed therapy, I think about symptomatic control and tumor control. The way we initially start out with this is through using the somatostatin analogs. In the United States, there are 2 that are available to us, octreotide LAR [long-acting release] and lanreotide. Octreotide LAR has been around for a very long time and is FDA approved for patients with carcinoid tumors for symptom control. Lanreotide has the most recent FDA approval of the somatostatin analogs and is FDA approved not only for symptom control in patients with neuroendocrine tumors of the GI [gastrointestinal] tract or pancreas but also for tumor control. There are some subtleties and nuances when you compare the 2.
Now, the 2 have not been compared head-to-head, so do we know which one is best to start out with? We really don’t. When patients come in to see me, if they’re doing well on whatever they’re on, I tend to keep them on it. If they’re not on anything, I tend to put them on the other. The goals are first to control the symptoms and second to try to control tumor growth. Sometimes patients need a little bit more than just the somatostatin analogs. If I think that they need more than that, depending on where their primary tumor starts and the differentiation status or Ki 67, I may opt for chemotherapy. What I tend to use, especially for the lower-grade tumors, is a combination of capecitabine and temozolomide, or the CAPTEM regimen. When I use this, I talk to patients about what to expect side effect wise and prepare them. I see them on a monthly basis to see how they’re doing on this treatment. And then I generally look at scans after they’ve been on for 3 months and see what their scans do. If their scans look good and they’re otherwise tolerating the treatment, we press on for another 3 months. We can keep going on this.
Other options for treatment would be some of the targeted agents. Depending on where the site of origin is, we’ve got a couple. Everolimus is a targeted agent that we use in patients with pancreatic neuroendocrine tumors and also neuroendocrine tumors of the lung or GI tract. Sunitinib is another targeted agent that we use primarily for patients with pancreatic neuroendocrine tumors. Now, these agents tend to work well. Patients tend to tolerate them, but they can come with their share of side effects, so we watch them very closely, and we may need to make some dose adjustments along the way.
Beyond those, we talk about radionuclide therapy or peptide receptor radionuclide therapy, or PRRT. This is the latest thing to be FDA approved that we’re all very, very excited about. What this does is take that same octreotide molecule and link some radiation onto it. What happens is the octreotide serves as a vehicle for the radiation that goes to those somatostatin receptors and delivers that radiation to them. This was recently FDA approved, and we’re all very eager to start using this on a regular basis. We’ve been sending people to Europe to have this done for a number of years because they’ve been doing it over there for quite some time, and we’re finally able to do this in the United States.