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Therapies for Controlling Symptoms of NETs

Panelists: Simron Singh, MD, Odette Cancer Centre; Jonathan R. Strosberg, MD Moffitt Cancer Center
Published: Friday, Jan 11, 2019



Transcript: 

Jonathan R. Strosberg, MD: How active do you think somatostatin analogs are in controlling carcinoid syndrome?

Simron Singh, MD: Somatostatin analogs are the best treatment we have. They’re the mainstay of treating carcinoid syndrome. We often use high doses of somatostatin analogs to control patients, and we usually see excellent responses. There are, unfortunately, a minority of patients who still have ongoing symptoms despite using somatostatin analogs. Fortunately, we now have newer therapies available. We have systemic therapies available, like telotristat, which is an oral agent that can help decrease the production of serotonin. In the right patient, it can potentially have really meaningful results. Then we have other therapies like liver-directed therapy, which can be done to reduce tumor burden and hormonal burden for the patient. New things are coming across. We’re starting to learn more and more about the role of SBRT [stereotactic body radiation therapy], for example, and PRRT [peptide receptor radionuclide therapy] in controlling not only the tumor but the hormonal secretions. So we’ve got lots of options, but somatostatin analogs remain our mainstay of treatment.

Jonathan R. Strosberg, MD: And just to expand on that, the audience may be relatively unfamiliar with telotristat, which is an oral tryptophan hydroxylase inhibitor. It’s taken 3 times a day. Its primary indication is for control of refractory diarrhea. It was tested in patients who had 4 or more bowel movements a day on somatostatin analogs. It’s given in combination with octreotide or lanreotide for control of diarrhea. Its reduction on the incidence of carcinoid heart disease is speculated but remains unknown. And, of course, you mentioned liver-directed therapy, or liver embolization, which hasn’t really been studied much prospectively. However, there are dozens of institutional series showing an improvement of both the flushing and diarrhea in the large majority of patients who receive treatment. So it is an effective treatment for patients with liver-dominant tumors.

We now have a prospective randomized study comparing 3 different liver embolization modalities: bland embolization, for which we just infuse microparticles, versus 2 types of chemoembolization—standard chemoembolization and drug-eluting beads. Hopefully, that will provide us with more prospective data, on both the efficacy and toxicity of liver embolization.

I’m wondering if you could talk a little about the multidisciplinary team, which is obviously very important for NETs [neuroendocrine tumors].

Simron Singh, MD: Yes, I completely agree. At our clinic in Toronto, [Ontario], the multidisciplinary team is sort of the bedrock of how we treat these patients. In fact, our patients see multiple clinicians on the same day. We’ve already talked about the complexities in neuroendocrine cancer—understanding the heterogeneity, trying to control the cancer from an antiproliferative case, or trying to control its growth, as well as trying to control hormones and secretions. And then, with a lot of the medications we use, we see a lot of sequelae that we need to manage. So I think we need a really strong team. Teams can consist of different people in different ways, but I think the core members of a team are always going to be surgeons, oncologists, endocrinologists, nuclear medicine specialists, pathologists, gastroenterologists, radiologists, nurses, and supportive-care doctors. A social worker is also an important member of our team. So I think you really need a village to treat a neuroendocrine patient.

Jonathan R. Strosberg, MD: For most cancers, the surgeon is predominantly the specialist for early-stage disease. The medical oncologist is often important for either adjuvant therapy or systemic treatments. But NETs are unique. Liver-directed therapy plays such an important role, even in stage IV disease.

Simron Singh, MD: We can’t forget interventional radiologists.

Jonathan R. Strosberg, MD: And, of course, with peptide receptor radiotherapy, the nuclear medicine physicians are involved. An endocrinologist is sometimes involved if patients have hormonal symptoms. So it’s an unusual cancer in that sense.

Transcript Edited for Clarity

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Transcript: 

Jonathan R. Strosberg, MD: How active do you think somatostatin analogs are in controlling carcinoid syndrome?

Simron Singh, MD: Somatostatin analogs are the best treatment we have. They’re the mainstay of treating carcinoid syndrome. We often use high doses of somatostatin analogs to control patients, and we usually see excellent responses. There are, unfortunately, a minority of patients who still have ongoing symptoms despite using somatostatin analogs. Fortunately, we now have newer therapies available. We have systemic therapies available, like telotristat, which is an oral agent that can help decrease the production of serotonin. In the right patient, it can potentially have really meaningful results. Then we have other therapies like liver-directed therapy, which can be done to reduce tumor burden and hormonal burden for the patient. New things are coming across. We’re starting to learn more and more about the role of SBRT [stereotactic body radiation therapy], for example, and PRRT [peptide receptor radionuclide therapy] in controlling not only the tumor but the hormonal secretions. So we’ve got lots of options, but somatostatin analogs remain our mainstay of treatment.

Jonathan R. Strosberg, MD: And just to expand on that, the audience may be relatively unfamiliar with telotristat, which is an oral tryptophan hydroxylase inhibitor. It’s taken 3 times a day. Its primary indication is for control of refractory diarrhea. It was tested in patients who had 4 or more bowel movements a day on somatostatin analogs. It’s given in combination with octreotide or lanreotide for control of diarrhea. Its reduction on the incidence of carcinoid heart disease is speculated but remains unknown. And, of course, you mentioned liver-directed therapy, or liver embolization, which hasn’t really been studied much prospectively. However, there are dozens of institutional series showing an improvement of both the flushing and diarrhea in the large majority of patients who receive treatment. So it is an effective treatment for patients with liver-dominant tumors.

We now have a prospective randomized study comparing 3 different liver embolization modalities: bland embolization, for which we just infuse microparticles, versus 2 types of chemoembolization—standard chemoembolization and drug-eluting beads. Hopefully, that will provide us with more prospective data, on both the efficacy and toxicity of liver embolization.

I’m wondering if you could talk a little about the multidisciplinary team, which is obviously very important for NETs [neuroendocrine tumors].

Simron Singh, MD: Yes, I completely agree. At our clinic in Toronto, [Ontario], the multidisciplinary team is sort of the bedrock of how we treat these patients. In fact, our patients see multiple clinicians on the same day. We’ve already talked about the complexities in neuroendocrine cancer—understanding the heterogeneity, trying to control the cancer from an antiproliferative case, or trying to control its growth, as well as trying to control hormones and secretions. And then, with a lot of the medications we use, we see a lot of sequelae that we need to manage. So I think we need a really strong team. Teams can consist of different people in different ways, but I think the core members of a team are always going to be surgeons, oncologists, endocrinologists, nuclear medicine specialists, pathologists, gastroenterologists, radiologists, nurses, and supportive-care doctors. A social worker is also an important member of our team. So I think you really need a village to treat a neuroendocrine patient.

Jonathan R. Strosberg, MD: For most cancers, the surgeon is predominantly the specialist for early-stage disease. The medical oncologist is often important for either adjuvant therapy or systemic treatments. But NETs are unique. Liver-directed therapy plays such an important role, even in stage IV disease.

Simron Singh, MD: We can’t forget interventional radiologists.

Jonathan R. Strosberg, MD: And, of course, with peptide receptor radiotherapy, the nuclear medicine physicians are involved. An endocrinologist is sometimes involved if patients have hormonal symptoms. So it’s an unusual cancer in that sense.

Transcript Edited for Clarity
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