TABLE 1. Somatostatin Analogues in the Treatment of Gastroenteropancreatic Neuroendocrine Tumors Somatostatin analogue Administration Dosage Octreotid

Size: px
Start display at page:

Download "TABLE 1. Somatostatin Analogues in the Treatment of Gastroenteropancreatic Neuroendocrine Tumors Somatostatin analogue Administration Dosage Octreotid"

Transcription

1 REVIEW SOMATOSTATIN ANALOGUES IN GEPNETS Somatostatin Analogues in the Treatment of Gastroenteropancreatic Neuroendocrine Tumors THIERRY DELAUNOIT, MD; JOSEPH RUBIN, MD; FLORENCE NECZYPORENKO, MD; CHARLES ERLICHMAN, MD; AND TIMOTHY J. HOBDAY, MD Gastroenteropancreatic neuroendocrine tumors constitute a heterogeneous group of neoplasms that are often associated with typical symptoms due to excessive and uncontrolled release of diverse hormones. Because these tumors are usually slow growing, surgery is the cornerstone of treatment. However, these rare tumors can present with rapid progression that requires aggressive systemic therapy or diffuse metastatic disease not amenable to surgical palliation. For most patients, medical approaches are necessary at some point in the course of their disease, especially since most tumors are at an advanced stage at the time of diagnosis. Most gastroenteropancreatic neuroendocrine tumors express high levels of somatostatin receptors, which are bound by somatostatin or its synthetic analogues. These agents, alone or combined with other therapies, such as interferon or radioisotopes, are therefore used frequently to control hormone-related symptoms and, for some patients, the growth of the disease itself. This article reviews the evidence for the use of somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumors based on a MEDLINE search of literature published from January 1970 to July Mayo Clin Proc. 2005;80(4): GEPNET = gastroenteropancreatic neuroendocrine tumor; PR = partial response; SST = somatostatin; SSTR = SST receptor From the Department of Oncology (T.D., J.R., C.E., T.J.H.) and Molecular Medicine Program (F.N.), Mayo Clinic College of Medicine, Rochester, Minn. Drs Delaunoit and Neczyporenko are now with the Institut Jules Bordet, Brussels, Belgium. Dr Delaunoit has been supported by Amis de l Institut Bordet and a grant from Yvonne and Thomas Rucquois. Individual reprints of this article are not available. Address correspondence to Timothy J. Hobday, MD, Department of Oncology, Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN ( hobday.timothy@mayo.edu) Mayo Foundation for Medical Education and Research Gastroenteropancreatic neuroendocrine tumors (GEPNETs), including gastrointestinal carcinoid tumors and pancreatic islet cell carcinomas, are rare malignancies derived from neuroendocrine cells scattered along the gastrointestinal system. GEPNETs are often characterized by the production of hormones and bioactive substances. They are generally slowly progressive and may present with typical clinical symptoms related to excessive and uncontrolled release of diverse hormones. Production of serotonin may cause flushing and diarrhea, as in the classic carcinoid syndrome. Catecholaminergic and neuroglycopenic symptoms, such as fatigue, weakness, tremulousness, and hunger, may result from excess insulin. Production of adrenocorticotropic hormone or cortisol may cause the myriad symptoms of steroid hormone excess. Hypergastrinemia may cause diarrhea and fulminant peptic ulcer disease, whereas glucagon production may result in diabetes mellitus and necrolytic migratory erythema. Some patients may have excessive production of multiple hormones. 1,2 Treatment of such a heterogeneous group of tumors and symptoms represents a challenge for the physician. The choice of treatment for GEPNETs depends primarily on the pathologic differentiation and stage at diagnosis but also on the presence of symptoms related to hormonal secretion. Often, these tumors are slow growing and sometimes can be managed with clinical observation only. However, they can display accelerated progression, requiring a much more aggressive strategy. Surgery remains the only curative approach to GEPNETs. However, these malignant tumors are generally diagnosed at an advanced stage when cure cannot be achieved. To date, several approaches have been used to control tumor growth in advanced disease, whether due to bulky disease or hormonal secretions, and to improve quality of life in symptomatic patients. Surgery should always be considered an option, even in advanced cases, to control symptoms related to tumor bulk and/or excessive hormone production. Somatostatin (SST) analogues are important agents in the medical treatment of GEPNETs. They not only can reduce secretion of hormones and hence control hormone-related symptoms but also are capable of controlling disease progression. This article reviews the evidence for the use of SST analogues in the treatment of GEPNETs based on a MEDLINE search of literature published from January 1970 to July Primary search terms included carcinoid tumor, islet cell carcinoma, neuroendocrine tumor,, and interferon. SST AND ITS ANALOGUES Somatostatin is a natural small cyclic peptide hormone synthesized as part of a large prohormone molecule that is enzymatically cleaved into its active form. Somatostatin is secreted at multiple sites throughout the human body, including the digestive system. 3 Its activity is mediated through 5 specific SST receptors (SSTRs) (SSTR-1 to SSTR-5) located on the membrane of the target cells. Somatostatin receptor 3 mediates apoptosis in endocrine cells, whereas inhibition of cell proliferation is mediated by activation of SSTR-1, SSTR-2, and SSTR-5, inducing antimitotic effects 502

2 TABLE 1. Somatostatin Analogues in the Treatment of Gastroenteropancreatic Neuroendocrine Tumors Somatostatin analogue Administration Dosage Octreotide Subcutaneous µg every 8 h Long-acting Intramuscular mg every 28 d Lanreotide Subcutaneous µg every 8 h Prolonged-release Intramuscular 30 mg every 14 d in most cell types. 4-7 Expression of SSTR-2 and SSTR-5 is particularly high in GEPNETs. Both SSTR-2 and SSTR-5 are found in approximately 90% and 80% of tumors, respectively, making these tumors potentially sensitive to hormonal treatment that targets these receptors. 8,9 The presence of SSTR in malignant GEPNETs appears to correlate with response to SST analogues, as shown by Kvols et al. 10 They performed autoradiography using 125 I-Tyr 3 -SMS , a tyrosine-substituted analogue of, in 8 patients with GEPNETs. All were strongly positive for SSTR and showed symptomatic improvement along with a decrease in secretion of at least 1 hormone when treated with. 10 Because of extremely rapid blood clearance and postinfusion hormonal hypersecretion rebound, native SST is no longer used in the treatment of GEPNETs and has been replaced by synthetic analogues. The available SST analogues, and (Table 1), have been shown to have a strong affinity for SSTR-2 and SSTR-5 and demonstrate, in vitro and in vivo, antisecretory and antiproliferative effects but no postadministration hypersecretion rebound. 8,10 Both and have a longer duration of action compared with SST and can be administered subcutaneously or intramuscularly every 8 hours. Prolonged-release formulations now allow drug administration every 2 to 4 weeks. Both and have been shown to be efficacious in managing symptoms and tumor progression compared with standard doses of short-acting SST analogues. 11,12 Only is available in the United States. During the past 30 years, several studies have been performed to assess the tolerability and efficacy of different types and doses of SST analogues in GEPNETs, including pancreatic neuroendocrine tumors and carcinoid tumors. 7,11,13-31 The results of these studies are summarized in Table 2. All studies have assessed treatment by radiological objective response, hormonal response, or both. In most of the trials performed to date, symptomatic improvement has also been evaluated. No major difference has been observed among the various agents and modes of administration. In general, SST analogues are safe, easy to use, and generally well tolerated, with most patients experiencing at most mild adverse effects. Flatulence, diarrhea, and abdominal pain are seen in less than 10% of patients. Steatorrhea, nausea, vomiting, hyperglycemia or hypoglycemia, leg cramps, blurred vision, night sweats, or pain at injection site is experienced less often. With long-term use of SST analogues, cholelithiasis has been reported in 20% or more of patients. Treatment discontinuation related to adverse effects is rare. Objective tumor responses occur in 5% to 15% of patients and appear to be more frequent in those with carcinoid tumors. Stable disease is observed in approximately 40% of treated patients. Biological response and symptomatic improvement are seen in a large proportion of patients (Tables 2 and 3), with a median duration of response between 6 and 17 months. On the basis of these studies, SST analogues appear to be useful in the management of symptomatic disease related to either hormonal secretion or tumor burden. TABLE 2. Octreotide Studies in Gastroenteropancreatic Neuroendocrine Tumors* No. of Response (%) Reference patients Agent Dosage OR SD BR SR Arnold et al, Octreotide 200 µg 3 times daily NR Maton et al, Octreotide Various doses Kvols et al, Octreotide µg 3 times daily NR NR Ruszniewski et al, Octreotide 200 µg twice daily NR NR Eriksson et al, Octreotide 100 µg twice to 3 times daily NR Eriksson & Oberg, Octreotide 100 µg twice daily NR NR di Bartolomeo et al, Octreotide µg 3 times daily Saltz et al, Octreotide 250 µg 3 times daily Ricci et al, Long-acting 20 mg/mo Shojamanesh et al, Long-acting mg/mo 6 47 NR NR Tomassetti et al, Long-acting 20 mg/mo Rubin et al, vs Octreotide vs µg/d (total dose) vs NR NR NR 58 vs 22/20/25 long-acting 10/20/30 mg/mo 67/71/62 *BR = biochemical response; NR = not reported; OR = objective response; SD = stable disease; SR = symptomatic response. Combined end point. 503

3 TABLE 3. Lanreotide Studies in Gastroenteropancreatic Neuroendocrine Tumors* No. of Response (%) Reference patients Agent Dosage OR SD BR SR Eriksson et al, Lanreotide 4 mg 3 times daily NR Imam et al, Lanreotide 4 mg 3 times daily Faiss et al, Lanreotide 5 mg 3 times daily NR NR Ricci et al, Prolonged-release 30 mg every 14 d Scherubl et al, Prolonged-release 30 mg every d NR 39 NR 86/42/50, F/D/A Tomassetti et al, Prolonged-release 30 mg every 10 d NR 100 Ruszniewski et al, Prolonged-release 30 mg every 14 d 0 NR 18 39/30, F/D Wymenga et al, Prolonged-release 30 mg every 14 d *A = abdominal pain; BR = biochemical response; D = diarrhea; F = flushing; NR = not reported; OR = objective response; SD = stable disease; SR = symptomatic response. Several authors have suggested a dose-dependent antiproliferative effect of or on GEPNET growth. Imam et al 7 evaluated apoptotic effects of on neuroendocrine tumors using BON-1, a human serotonin-secreting pancreatic endocrine tumor cell line xenografted into nude mice. They showed a 3-fold increase in apoptotic cells in mice receiving treatment with highdose (600 mg/kg daily) compared with a placebo group (P<.001). Standard doses of ( µg/d) or (30 mg every 14 days) seemed slightly less effective than high doses of both drugs. In parallel to their preclinical study, Imam et al also studied apoptosis of tissue samples in 8 patients with neuroendocrine tumors treated with high doses of (12 mg/d) and 8 patients treated with interferon (4 patients), standard-dose SST analogues (3 patients), or both (1 patient). The percentage of apoptotic cells was correlated with clinical outcome. After 6 and 12 months of treatment, 5 patients treated with high-dose showed a biochemical response, 4 of whom also showed an increase in apoptotic index. No objective response was seen. None of the 8 patients treated in the other cohort showed any increase in apoptotic cells. 7 Of 19 patients with progressive GEPNETs treated with high-dose (12 mg/d), Eriksson et al 16 reported 1 patient with partial response (PR) and 12 with stable disease. Induction of apoptosis, determined by posttreatment tumor biopsies, was observed in patients with biochemical and radiological responses as well as those with stable disease. This induction of apoptosis suggests potential activation of SSTR-3, which mediates apoptosis, when high doses of SST analogues are used. Faiss et al 24 reported an overall response rate of 6.7% and 11 patients with stable disease in a trial that used a high dose of (15 mg/d) in 30 patients with advanced and progressive GEPNETs. The clinical outcomes in these small phase 2 studies are not clearly superior to those observed in the literature with regular doses. On the basis of these observations, further studies are needed to assess the exact role of high doses of SST analogues and the SST/ SSTR-3 pathway in induction of apoptosis and control of growth in GEPNETs. Currently, no convincing evidence exists to support the use of SST analogues at high doses. The tumor growth rate before treatment seems to have a significant predictive value for tumor response to SST analogues. Aparicio et al 32 showed 76% disease stabilization in a group defined as having slowly progressing disease compared with only 33% in patients classified as having rapidly progressing disease. More recently, another study, which included 15 patients with gastrinomas, showed that none of the patients responding to therapy belonged to the group defined as having rapidly progressing disease. 26 Therefore, tumor growth rate before treatment must be taken into account when SST analogues are considered as therapy for disease progression. Some authors have suggested that there is incomplete cross-resistance between the SST analogues and. Ricci et al 31 studied 15 patients previously treated with long-acting and showed that 1 and 6 patients experienced radiological PR and stable disease, respectively, when treated with long-acting. The same group administered long-acting to 5 patients previously treated with subcutaneous. 29 Objective, symptomatic, and biochemical responses were observed in 1, 2, and 1 patients, respectively. These results, although interesting, were achieved in small numbers of patients and therefore allow no firm conclusions. Few data are available regarding any benefit of SST analogues on survival of patients with GEPNETs. To date, no prospective randomized trial has been performed in patients with GEPNETs treated with SST analogues compared with observation. Additional studies are necessary to determine any convincing effect of SST analogues on survival. 504

4 SST ANALOGUES IN COMBINATION WITH INTERFERON ALFA Somatostatin analogues and interferon alfa, used as single agents, are safe and have some activity for progressive GEPNETs. Combination therapies have been evaluated in clinical trials. Adding interferon alfa ( IU 3 times a week) to the regimen of patients previously treated with alone was shown to produce biochemical responses in 77% of the patients enrolled in the study of Tiensuu Janson et al 33 without objective tumor response. Frank et al 34 described their experience with interferon alfa, IU twice a week, in 21 patients with progressive GEPNETs, 16 of whom were previously treated with. They observed 1 patient with a complete response and 13 with stable disease, 11 of whom were previously treated with. Biochemical response, with more than 50% reduction of hormone secretion, was achieved in 69% of patients. More recently, Fjallskog et al 35 published their results in 16 patients with progressive pancreatic neuroendocrine tumors treated with various doses of interferon alfa ( IU 3-7 d/wk, titrated to toxicity); 3 had PR and 11 had stable disease. Median duration of response was 23 months, whereas it was 13 months for stable disease. Interestingly, all patients previously treated with SST analogues experienced stable disease, whereas 1 and 5 patients previously treated with interferon alfa monotherapy had PR and stable disease, respectively. Biochemical responses were observed in 10 patients, with a median duration of 22 months. In contrast to these studies, Faiss et al 36 showed, in a prospective, randomized, multicenter trial, that the combination of and interferon alfa ( IU 3 times a week) had no higher antiproliferative effect than that of monotherapy with or interferon alfa in 80 therapynaive patients with progressive and metastatic GEPNETs. However, hormone-related symptoms were significantly better controlled with the combination. The toxic effects reported in these studies were described as moderate and were predominantly related to interferon alfa (fever, anorexia, depression, confusion, arthralgia, and pain at injection site). Two patients experienced grade 3 confusion responsible for treatment cessation (considered a cortical neurologic toxic effect) in the study by Fjallskog et al. 35 The randomized trial by Faiss et al reported that toxic effects that led to treatment cessation were more frequent with combination therapy (7/28) than with each agent taken separately (4/27 with interferon alfa and 3/25 with ). However, these differences were not statistically significant. Hormonal control and objective response have been observed with the combination of interferon alfa and SST analogues in patients previously treated with one of the agents. However, the combination of both agents in therapy-naive patients does not seem to be superior to monotherapy with either interferon alfa or SST analogue for objective response. RADIOLABELED SST ANALOGUES The high-level expression of SSTRs on various tumor cells has provided the molecular basis for successful use of radiolabeled SST analogues as either tumor tracers or therapeutic agents. Several radionuclide agents have been combined with SST analogues, allowing successful detection of tumors that express SSTR. Pairing SST analogues with therapeutic high-energy emitting radionuclides therefore represents a clear opportunity to treat GEPNETs. Several preclinical and clinical studies have assessed the feasibility, efficacy, and tolerability of different radiolabeled peptides in the treatment of tumor-expressing SSTRs, most commonly with 90 Y-DOTA-, an yttrium-90 labeled analogue. 37 Neuroendocrine tumors are not only characterized by a usually high level of SSTR but also are well vascularized, an important condition for proper diffusion of radiolabeled peptides into the tumor mass. A phase 2 study published by Waldherr et al 38 evaluated 90 Y-DOTA- in the treatment of 39 patients with gastroenteropancreatic and bronchial carcinoid tumors. Overall, clinical symptoms were reduced significantly in 63% of the patients, whereas the objective response rate was 23%. Approximately one fourth of the patients experienced grade 3 or higher lymphocytopenia. Nausea and vomiting were the most common nonhematologic toxic effects, encountered in approximately one third of the cohort. Paganelli et al 39 studied the efficacy of 90 Y-DOTA in 87 patients with neuroendocrine tumors that expressed SSTR-2, 50 of whom had GEPNETs. Interestingly, among 66 patients who were responding to therapy before 90 Y-DOTA- treatment, 28% achieved an objective response, including a 5% complete response and 23% PR. The median duration of response was 24 months. Gastrointestinal adverse effects were mild and included nausea and vomiting, which occurred in approximately 50% of patients. Overall, radiolabeled SST analogues have shown some activity in controlling tumor growth of GEPNETs. Also, clinical symptoms have been reduced significantly. Toxic effects encountered have been manageable with adequate supportive care. Therefore, radiolabeled SST analogues constitute a promising alternative for treating patients with progressive and symptomatic disease. The results of larger ongoing studies are eagerly awaited. 505

5 CONCLUSION Somatostatin analogues are clearly safe and effective in controlling symptoms and hormonal secretions in GEPNETs but have limited ability to induce responses. Combination therapy with interferon alfa offers another approach to controlling disease symptoms in patients responding to treatment with SST analogues, although at the cost of increased toxic effects and little evidence of objective responses. Also, radiolabeled SST analogues may be helpful in controlling tumor growth and symptoms related to hormonal secretions and/or bulky disease. More knowledge about the SSTR subtypes, particularly SSTR-3, and their interrelation with intracellular pathways involved in proliferation and apoptosis may eventually lead to new palliative treatments for patients with GEPNETs. Combinations with novel targeted therapies that inhibit angiogenic and growth factor receptor pathways hold promise for improved outcome for these patients. REFERENCES 1. Moertel CG. Karnofsky memorial lecture: an odyssey in the land of small tumors. J Clin Oncol. 1987;5: Oberg K. Neuroendocrine gastrointestinal tumors a condensed overview of diagnosis and treatment. Ann Oncol. 1999;10(suppl 2):S3-S8. 3. Hejna M, Schmidinger M, Raderer M. The clinical role of somatostatin analogues as antineoplastic agents: much ado about nothing? Ann Oncol. 2002;13: Buscail L, Delesque N, Esteve JP, et al. Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subtypes SSTR1 and SSTR2. Proc Natl Acad Sci U S A. 1994;91: Buscail L, Esteve JP, Saint-Laurent N, et al. Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms. Proc Natl Acad Sci U S A. 1995;92: Sharma K, Patel YC, Srikant CB. Subtype-selective induction of wildtype p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol Endocrinol. 1996;10: Imam H, Eriksson B, Lukinius A, et al. Induction of apoptosis in neuroendocrine tumors of the digestive system during treatment with somatostatin analogs. Acta Oncol. 1997;36: Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ. Octreotide. N Engl J Med. 1996;334: Wulbrand U, Wied M, Zofel P, Goke B, Arnold R, Fehmann H. Growth factor receptor expression in human gastroenteropancreatic neuroendocrine tumours. Eur J Clin Invest. 1998;28: Kvols LK, Reubi JC, Horisberger U, Moertel CG, Rubin J, Charboneau JW. The presence of somatostatin receptors in malignant neuroendocrine tumor tissue predicts responsiveness to. Yale J Biol Med. 1992;65: Rubin J, Ajani J, Schirmer W, et al. Octreotide acetate long-acting formulation versus open-label subcutaneous acetate in malignant carcinoid syndrome. J Clin Oncol. 1999;17: Dogliotti L, Tampellini M, Stivanello M, Gorzegno G, Fabiani L. The clinical management of neuroendocrine tumors with long-acting repeatable (LAR) : comparison with standard subcutaneous therapy. Ann Oncol. 2001;12(suppl 2):S105-S Saltz L, Kemeny N, Schwartz G, Kelsen D. A phase II trial of alphainterferon and 5-fluorouracil in patients with advanced carcinoid and islet cell tumors. Cancer. 1994;74: Arnold R, Trautmann ME, Creutzfeldt W, et al. Somatostatin analogue and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours. Gut. 1996;38: di Bartolomeo M, Bajetta E, Buzzoni R, et al. Clinical efficacy of in the treatment of metastatic neuroendocrine tumors: a study by the Italian Trials in Medical Oncology Group. Cancer. 1996;77: Eriksson B, Renstrup J, Imam H, Oberg K. High-dose treatment with of patients with advanced neuroendocrine gastrointestinal tumors: clinical and biological effects. Ann Oncol. 1997;8: Wymenga AN, Eriksson B, Salmela PI, et al. Efficacy and safety of prolonged-release in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms. J Clin Oncol. 1999;17: Eriksson B, Janson ET, Bax ND, et al. The use of new somatostatin analogues, and octastatin, in neuroendocrine gastro-intestinal tumours. Digestion. 1996;57(suppl 1): Long RG, Barnes AJ, Adrian TE, et al. Suppression of pancreatic endocrine tumour secretion by long-acting somatostatin analogue. Lancet. 1979; 2: Maton PN, Gardner JD, Jensen RT. Use of long-acting somatostatin analog SMS in patients with pancreatic islet cell tumors. Dig Dis Sci. 1989;34(3, suppl):28s-39s. 21. Scherubl H, Wiedenmann B, Riecken EO, Thomas F, Bohme E, Rath U. Treatment of the carcinoid syndrome with a depot formulation of the somatostatin analogue [letter]. Eur J Cancer. 1994;30A: Ruszniewski P, Ramdani A, Cadiot G, Lehy T, Mignon M, Bonfils S. Long-term treatment with in patients with the Zollinger-Ellison syndrome. Eur J Clin Invest. 1993;23: Kvols LK, Buck M, Moertel CG, et al. Treatment of metastatic islet cell carcinoma with a somatostatin analogue (SMS ). Ann Intern Med. 1987;107: Faiss S, Rath U, Mansmann U, et al. Ultra-high-dose treatment in patients with metastatic neuroendocrine gastroenteropancreatic tumors. Digestion. 1999;60: Tomassetti P, Migliori M, Gullo L. Slow-release treatment in endocrine gastrointestinal tumors. Am J Gastroenterol. 1998;93: Shojamanesh H, Gibril F, Louie A, et al. Prospective study of the antitumor efficacy of long-term treatment in patients with progressive metastatic gastrinoma. Cancer. 2002;94: Eriksson B, Oberg K. An update of the medical treatment of malignant endocrine pancreatic tumors. Acta Oncol. 1993;32: Eriksson B, Skogseid B, Lundqvist G, Wide L, Wilander E, Oberg K. Medical treatment and long-term survival in a prospective study of 84 patients with endocrine pancreatic tumors. Cancer. 1990;65: Ricci S, Antonuzzo A, Galli L, et al. Long-acting depot in the treatment of patients with advanced neuroendocrine tumors. Am J Clin Oncol. 2000;23: Ruszniewski P, Ducreux M, Chayvialle JA, et al. Treatment of the carcinoid syndrome with the longacting somatostatin analogue : a prospective study in 39 patients. Gut. 1996;39: Ricci S, Antonuzzo A, Galli L, et al. Octreotide acetate long-acting release in patients with metastatic neuroendocrine tumors pretreated with. Ann Oncol. 2000;11: Aparicio T, Ducreux M, Baudin E, et al. Antitumour activity of somatostatin analogues in progressive metastatic neuroendocrine tumours. Eur J Cancer. 2001;37: Tiensuu Janson EM, Ahlstrom H, Andersson T, Oberg KE. Octreotide and interferon alfa: a new combination for the treatment of malignant carcinoid tumours. Eur J Cancer. 1992;28A: Frank M, Klose KJ, Wied M, Ishaque N, Schade-Brittinger C, Arnold R. Combination therapy with and alpha-interferon: effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors. Am J Gastroenterol. 1999;94: Fjallskog ML, Sundin A, Westlin JE, Oberg K, Janson ET, Eriksson B. Treatment of malignant endocrine pancreatic tumors with a combination of alpha-interferon and somatostatin analogs. Med Oncol. 2002;19: Faiss S, Pape UF, Bohmig M, et al. Prospective, randomized, multicenter trial on the antiproliferative effect of, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol. 2003;21: De Jong M, Valkema R, Jamar F, et al. Somatostatin receptor-targeted radionuclide therapy of tumors: preclinical and clinical findings. Semin Nucl Med. 2002;32: Waldherr C, Pless M, Maecke HR, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med. 2002;43: Paganelli G, Bodei L, Handkiewicz Junak D, et al. 90Y-DOTA-D-Phe1- Try3- in therapy of neuroendocrine malignancies. Biopolymers. 2002;66:

Octreotide LAR in neuroendocrine tumours a summary of the experience

Octreotide LAR in neuroendocrine tumours a summary of the experience Endocrinology in oncology Review article Octreotide LAR in neuroendocrine tumours a summary of the experience Agnieszka Kolasińska-Ćwikła, MD, PhD Department of Chemotherapy, Oncology Clinic, Maria Sklodowska-Curie

More information

Gastrinoma: Medical Management. Haley Gallup

Gastrinoma: Medical Management. Haley Gallup Gastrinoma: Medical Management Haley Gallup Also known as When to put your knife down Gastrinoma Definition and History Diagnosis Historic Management Sporadic vs MEN-1 Defining surgical candidates Nonsurgical

More information

Targeted Radionuclide Therapy with 90 Y-DOTATOC in Patients with Neuroendocrine Tumors

Targeted Radionuclide Therapy with 90 Y-DOTATOC in Patients with Neuroendocrine Tumors Targeted Radionuclide Therapy with 90 Y-DOTATOC in Patients with Neuroendocrine Tumors FLAVIO FORRER 1, CHRISTIAN WALDHERR 1, HELMUT R. MAECKE 2 and JAN MUELLER-BRAND 1 1 Institute of Nuclear Medicine

More information

LONG-TERM MANAGEMENT OF THE CARCINOID SYNDROME

LONG-TERM MANAGEMENT OF THE CARCINOID SYNDROME Acta Oncologica Vol. 32, No. 2, pp. 225-229, 1993 LONG-TERM MANAGEMENT OF THE CARCINOID SYNDROME Treatment with octreotide alone and in combination with alpha-interferon EVA TIENSUU JANSON and KJELL OBERG

More information

TRACTAMENT ONCOLÒGIC DELS TUMORS NEUROENDOCRINS METASTÀSICS

TRACTAMENT ONCOLÒGIC DELS TUMORS NEUROENDOCRINS METASTÀSICS TRACTAMENT ONCOLÒGIC DELS TUMORS NEUROENDOCRINS METASTÀSICS Jaume Capdevila Unitat de Tumors GI i Endocrins Hospital Universitari Vall d Hebron Barcelona Experts, acollidors i solidaris OUTLINE BACKGROUND

More information

MEDICAL MANAGEMENT OF METASTATIC GEP-NET

MEDICAL MANAGEMENT OF METASTATIC GEP-NET MEDICAL MANAGEMENT OF METASTATIC GEP-NET Jeremy Kortmansky, MD Associate Professor of Clinical Medicine Yale Cancer Center DISCLOSURES: NONE Introduction Gastrointestinal and pancreatic neuroendocrine

More information

Systemic Therapy for Gastroenteropancreatic (GEP) Neuroendocrine Tumors and Lung Carcinoid

Systemic Therapy for Gastroenteropancreatic (GEP) Neuroendocrine Tumors and Lung Carcinoid Systemic Therapy for Gastroenteropancreatic (GEP) Neuroendocrine Tumors and Lung Carcinoid The Medical Oncology Perspective Nevena Damjanov, MD Associate professor Abramson Cancer Center of the University

More information

Corporate Medical Policy

Corporate Medical Policy Corporate Medical Policy File Name: Origination: Last CAP Review: Next CAP Review: Last Review: somatostatin_analogs 7/2016 7/2017 7/2018 7/2017 Description of Procedure or Service Somatostatin, a hypothalamic

More information

Neuroendocrine Tumors

Neuroendocrine Tumors Neuroendocrine Tumors Neuroendocrine tumors arise from cells that release a hormone in response to a signal from the nervous system. Neuro refers to the nervous system. Endocrine refers to the hormones.

More information

Gastrointestinal Neuroendocrine Tumors: A Closer Look at the Characteristics of These Diverse Tumors

Gastrointestinal Neuroendocrine Tumors: A Closer Look at the Characteristics of These Diverse Tumors Gastrointestinal Neuroendocrine Tumors: A Closer Look at the Characteristics of These Diverse Tumors Jaume Capdevila, MD, PhD Vall d'hebron University Hospital Vall d'hebron Institute of Oncology (VHIO)

More information

SOMATOSTATIN RECEPTORS IN HEPATOCELLULAR CARCINOMA. Marie LEQUOY Saint-Antoine Hospital, Department of Hepatology, Paris, France

SOMATOSTATIN RECEPTORS IN HEPATOCELLULAR CARCINOMA. Marie LEQUOY Saint-Antoine Hospital, Department of Hepatology, Paris, France SOMATOSTATIN RECEPTORS IN HEPATOCELLULAR CARCINOMA Marie LEQUOY Saint-Antoine Hospital, Department of Hepatology, Paris, France Somatostatin : SST Somatostatin (SST) protein : 2 active forms (alternative

More information

Case Report. Ameya D. Puranik, MD, FEBNM; Harshad R. Kulkarni, MD; Aviral Singh, MD; Richard P. Baum, MD, PhD ABSTRACT

Case Report. Ameya D. Puranik, MD, FEBNM; Harshad R. Kulkarni, MD; Aviral Singh, MD; Richard P. Baum, MD, PhD ABSTRACT Case Report 8-YEAR SURVIVAL WITH A METASTATIC THYMIC NEUROENDOCRINE TUMOR: EMPHASIS ON REDEFINING TREATMENT OBJECTIVES USING PERSONALIZED PEPTIDE RECEPTOR RADIONUCLIDE THERAPY WITH 177 Lu- AND 90 Y-LABELED

More information

Patient information file

Patient information file Internal irradiation of neuroendocrine tumors with Yttrium-90-DOTATOC, a radiolabeled somatostatin analogue Patient information file Ladies and Gentlemen You are diagnosed with a neuroendocrine tumor and

More information

Pasireotide Long-Acting Repeatable (Signifor) for acromegaly first and second line

Pasireotide Long-Acting Repeatable (Signifor) for acromegaly first and second line Pasireotide Long-Acting Repeatable (Signifor) for acromegaly first and second line December 2010 This technology summary is based on information available at the time of research and a limited literature

More information

Carcinoid tumors are rare, slowly progressive tumors principally of

Carcinoid tumors are rare, slowly progressive tumors principally of 770 Treatment of Carcinoid Syndrome A Prospective Crossover Evaluation of Lanreotide versus Octreotide in Terms of Efficacy, Patient Acceptability, and Tolerance Dermot O Toole, M.D. 1 Michel Ducreux,

More information

PRINCESS MARGARET CANCER CENTRE CLINICAL PRACTICE GUIDELINES

PRINCESS MARGARET CANCER CENTRE CLINICAL PRACTICE GUIDELINES PRINCESS MARGARET CANCER CENTRE CLINICAL PRACTICE GUIDELINES GASTROINTESTINAL NEUROENDOCRINE GASTRO-ENTERO-PANCREATIC TUMOURS GI Site Group Neuroendocrine gastro-entero-pancreatic tumours Authors: Dr.

More information

Review of Gastrointestinal Carcinoid Tumors: Latest Therapies

Review of Gastrointestinal Carcinoid Tumors: Latest Therapies Review of Gastrointestinal Carcinoid Tumors: Latest Therapies Arvind Dasari, MD, MS Department of Gastrointestinal Medical Oncology The University of Texas MD Anderson Cancer Center Houston, TX, USA Neuroendocrine

More information

MEDICAL POLICY EFFECTIVE DATE: 06/21/07 REVISED DATE: 05/14/08, 04/16/09, 03/18/10, 03/17/11, 03/15/12, 02/21/13, 02/20/14, 02/19/15

MEDICAL POLICY EFFECTIVE DATE: 06/21/07 REVISED DATE: 05/14/08, 04/16/09, 03/18/10, 03/17/11, 03/15/12, 02/21/13, 02/20/14, 02/19/15 MEDICAL POLICY PAGE: 1 OF: 6 If the member's subscriber contract excludes coverage for a specific service it is not covered under that contract. In such cases, medical policy criteria are not applied.

More information

SOMATULINE DEPOT (lanreotide acetate)

SOMATULINE DEPOT (lanreotide acetate) SOMATULINE DEPOT (lanreotide acetate) Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical

More information

In patients with. gastroenteropancreatic. neuroendocrine neoplasms, SSTR subtyping may help to. predict the clinical outcome. following somatostatin

In patients with. gastroenteropancreatic. neuroendocrine neoplasms, SSTR subtyping may help to. predict the clinical outcome. following somatostatin In patients with gastroenteropancreatic neuroendocrine neoplasms, SSTR subtyping may help to predict the clinical outcome following somatostatin analog therapy. Annie Toja. Mediterranean Fishing Boats.

More information

Background. Capdevila J, et al. Ann Oncol. 2018;29(Suppl 8): Abstract 1307O. 1. Dasari A, et al. JAMA Oncol. 2017;3(10):

Background. Capdevila J, et al. Ann Oncol. 2018;29(Suppl 8): Abstract 1307O. 1. Dasari A, et al. JAMA Oncol. 2017;3(10): Efficacy of Lenvatinib in Patients With Advanced Pancreatic (pannets) and Gastrointestinal (ginets) WHO Grade 1/2 (G1/G2) Neuroendocrine Tumors: Results of the International Phase II TALENT Trial (GETNE

More information

Somatostatin receptor mediated diagnosis and treatment in gastrointestinal neuroendocrine

Somatostatin receptor mediated diagnosis and treatment in gastrointestinal neuroendocrine 62 Öberg K Roczniki Akademii Medycznej w Białymstoku Vol. 50, 2005 Annales Academiae Medicae Bialostocensis Somatostatin receptor mediated diagnosis and treatment in gastrointestinal neuroendocrine tumours

More information

Treatment of endocrine pancreatic tumors

Treatment of endocrine pancreatic tumors Acta Oncologica, 2005; 44: 329 /338 REVIEW ARTICLE Treatment of endocrine pancreatic tumors MARIE-LOUISE FJÄLLSKOG 1 & EVA TIENSUU JANSON 2 1 Departments of Oncology, Radiology and Clinical Immunology,

More information

Sandostatin LAR. Sandostatin LAR (octreotide acetate) Description

Sandostatin LAR. Sandostatin LAR (octreotide acetate) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.09 Subject: Sandostatin LAR Page: 1 of 5 Last Review Date: March 16, 2018 Sandostatin LAR Description

More information

Neuroendocrine Tumors: Just the Basics. George Fisher, MD PhD

Neuroendocrine Tumors: Just the Basics. George Fisher, MD PhD Neuroendocrine Tumors: Just the Basics George Fisher, MD PhD Topics that we will not discuss Some types of lung cancer: Small cell neuroendocrine lung cancer Large cell neuroendocrine lung cancer Some

More information

Teresa Alonso Gordoa Servicio Oncología Médica Hospital Universitario Ramón y Cajal

Teresa Alonso Gordoa Servicio Oncología Médica Hospital Universitario Ramón y Cajal Teresa Alonso Gordoa Servicio Oncología Médica Hospital Universitario Ramón y Cajal Incidence per 100,000 EPIDEMIOLOGY Incidence rates of neuroendocrine tumors by primary tumor site 1.4 1.2 1.0 0.8 0.6

More information

Peptide Receptor Radionuclide Therapy using 177 Lu octreotate

Peptide Receptor Radionuclide Therapy using 177 Lu octreotate Peptide Receptor Radionuclide Therapy using 177 Lu octreotate BLR Kam, Erasmus Medical Centre, Rotterdam DJ Kwekkeboom, Erasmus Medical Centre, Rotterdam Legal aspects As 177 Lu-[DOTA 0 -Tyr 3 ]octreotate

More information

WHAT TO EXPECT IN 2015? - Renuka Iyer, MD Associate Professor of Medicine, University at Buffalo Associate Professor of Oncology, Roswell Park Cancer

WHAT TO EXPECT IN 2015? - Renuka Iyer, MD Associate Professor of Medicine, University at Buffalo Associate Professor of Oncology, Roswell Park Cancer WHAT TO EXPECT IN 2015? - Renuka Iyer, MD Associate Professor of Medicine, University at Buffalo Associate Professor of Oncology, Roswell Park Cancer Institute Overview Diagnosis: Gallium scan Biomarkers

More information

Contemporary methods of therapy and follow-up of neuroendocrine tumours of the gastrointestinal tract and the pancreas

Contemporary methods of therapy and follow-up of neuroendocrine tumours of the gastrointestinal tract and the pancreas Wspolczesna Onkol 2012; 16 (5): 371 375 DOI: 10.5114/wo.2012.31764 Review The growing interest in neuroendocrine tumours is due to the dynamic growth of detection of this type of cancer. Neuroendocrine

More information

Peptide Receptor Radionuclide Therapy (PRRT) of NET

Peptide Receptor Radionuclide Therapy (PRRT) of NET Peptide Receptor Radionuclide Therapy (PRRT) of NET Dr. Tuba Kendi Associate Prof of Radiology, Mayo Clinic, Rochester, MN 2014 MFMER slide-1 Relevant Financial Relationship(s) None Off Label Usage None

More information

Neuroendocrine Tumors Positron Emission Tomography (PET) Imaging and Peptide Receptor Radionuclide Therapy

Neuroendocrine Tumors Positron Emission Tomography (PET) Imaging and Peptide Receptor Radionuclide Therapy Neuroendocrine Tumors Positron Emission Tomography (PET) Imaging and Peptide Receptor Radionuclide Therapy Lawrence Saperstein, M.D. Assistant Professor of Radiology and Biomedical Imaging Chief, Nuclear

More information

Pharmacy Prior Authorization Somatostatin Analogs Clinical Guideline

Pharmacy Prior Authorization Somatostatin Analogs Clinical Guideline Sandostatin LAR (octreotide) Signifor (pasireotide) Signifor LAR (pasireotide) Somatuline Depot (lanreotide) octreotide FDA Approved Indications: Acromegaly: Octreotide Injection is indicated to reduce

More information

9. Pharmacological therapy of neuroendocrine tumors

9. Pharmacological therapy of neuroendocrine tumors Tumori, 96: 847-857, 2010 9. Pharmacological therapy of neuroendocrine tumors Anja Rinke, Sergio Ricci, Emilio Bajetta, and Svetislav Jelic Evolving perspectives on antiproliferative effects of octreotide

More information

Neuroendocrine Tumors: Treatment Updates Highlights from the 2013 ASCO Annual Meeting. Chicago, IL, USA; May 30 - June 4, 2013

Neuroendocrine Tumors: Treatment Updates Highlights from the 2013 ASCO Annual Meeting. Chicago, IL, USA; May 30 - June 4, 2013 HIGHLIGHT ARTICLE Neuroendocrine Tumors: Treatment Updates Highlights from the 2013 ASCO Annual Meeting. Chicago, IL, USA; May 30 - June 4, 2013 Simon Khagi, Muhammad Wasif Saif Tufts Medical Center, Tufts

More information

Role of Somatostatin Analogues in the Treatment of Neuroendocrine Tumors

Role of Somatostatin Analogues in the Treatment of Neuroendocrine Tumors 109 Role of Somatostatin Analogues in the Treatment of Neuroendocrine Tumors Sujata Narayanan, MD, MS, and Pamela L. Kunz, MD Abstract Neuroendocrine tumors (NETs) are rare epithelial neoplasms with neuroendocrine

More information

Jaume Capdevila, MD GI and Endocrine Tumor Unit Vall d Hebron University Hospital Developmental Therapeutics Unit Vall d Hebron Institute of Oncology

Jaume Capdevila, MD GI and Endocrine Tumor Unit Vall d Hebron University Hospital Developmental Therapeutics Unit Vall d Hebron Institute of Oncology Jaume Capdevila, MD GI and Endocrine Tumor Unit Vall d Hebron University Hospital Developmental Therapeutics Unit Vall d Hebron Institute of Oncology OUTLINE Molecular Rationale for the use of SSAs in

More information

THERAPEUTIC RADIOPHARMACEUTICALS

THERAPEUTIC RADIOPHARMACEUTICALS UnitedHealthcare of California (HMO) UnitedHealthcare Benefits Plan of California (EPO/POS) UnitedHealthcare of Oklahoma, Inc. UnitedHealthcare of Oregon, Inc. UnitedHealthcare Benefits of Texas, Inc.

More information

EXOCRINE: 93% Acinar Cells Duct Cells. ENDOCRINE: 5% Alpha Cells Beta Cells Delta Cells Others

EXOCRINE: 93% Acinar Cells Duct Cells. ENDOCRINE: 5% Alpha Cells Beta Cells Delta Cells Others EXOCRINE: 93% Acinar Cells Duct Cells Digestive Enzymes Trypsin: Digests Proteins Lipases: Digests Fats Amylase: Digest Carbohydrates ENDOCRINE: 5% Alpha Cells Beta Cells Delta Cells Others Hormones Glucagon

More information

Recent developments of oncology in neuroendocrine tumors (NETs)

Recent developments of oncology in neuroendocrine tumors (NETs) Recent developments of oncology in neuroendocrine tumors (NETs) Marc Peeters MD, PhD Coordinator Multidisciplinary Oncological Center Antwerpen (MOCA) Head of the Oncology Department UZA, Professor in

More information

A New Proposal for Metabolic Classification of NENs Stefano Severi IRST Meldola Italy

A New Proposal for Metabolic Classification of NENs Stefano Severi IRST Meldola Italy RADIONUCLIDE THERAPY AND ALLIED SCIENCE President: Giovanni Paganelli Chairman: Maria Salvato Baltimore USA Domenico Barone Meldola Italy A New Proposal for Metabolic Classification of NENs Stefano Severi

More information

MEDICAL POLICY SUBJECT: PEPTIDE RECEPTOR RADIONUCLIDE THERAPY (PRRT)

MEDICAL POLICY SUBJECT: PEPTIDE RECEPTOR RADIONUCLIDE THERAPY (PRRT) MEDICAL POLICY SUBJECT: PEPTIDE RECEPTOR PAGE: 1 OF: 6 If a product excludes coverage for a service, it is not covered, and medical policy criteria do not apply. If a commercial product (including an Essential

More information

GI CARCINOID Dr Mussawar Iqbal Consultant Oncologist Hull and East Yorkshire Hospitals NHS Trust

GI CARCINOID Dr Mussawar Iqbal Consultant Oncologist Hull and East Yorkshire Hospitals NHS Trust GI CARCINOID Dr Mussawar Iqbal Consultant Oncologist Hull and East Yorkshire Hospitals NHS Trust Introduction Carcinoid was old term, introduced in 1906 by German pathologist Cancinoma like More recent

More information

MEDICAL POLICY SUBJECT: PEPTIDE RECEPTOR RADIONUCLIDE THERAPY (PRRT)

MEDICAL POLICY SUBJECT: PEPTIDE RECEPTOR RADIONUCLIDE THERAPY (PRRT) MEDICAL POLICY SUBJECT: PEPTIDE RECEPTOR RADIONUCLIDE THERAPY (PRRT) POLICY NUMBER: 7.01.78 CATEGORY: Technology Assessment EFFECTIVE DATE: 06/21/07 REVISED DATE: 05/14/08, 04/16/09, 03/18/10, 03/17/11,

More information

Peptide receptor radionuclide therapy of neuroendocrine tumors: Case series

Peptide receptor radionuclide therapy of neuroendocrine tumors: Case series Peptide receptor radionuclide therapy of neuroendocrine tumors: Case series Milovan Matović Summary Background: Peptide Receptor Radionuclide Therapy (PRRT) is novel and efficacious treatment of neuroendocrine

More information

Medical Policy An independent licensee of the Blue Cross Blue Shield Association

Medical Policy An independent licensee of the Blue Cross Blue Shield Association Xermelo (telotristat) Page 1 of 5 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Xermelo (telotristat) Prime Therapeutics will review Prior Authorization requests

More information

original article introduction original article

original article introduction original article Annals of Oncology 21: 787 794, 2010 doi:10.1093/annonc/mdp372 Published online 15 October 2009 Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic

More information

Endocrine pancreatic tumors: factors correlated with survival

Endocrine pancreatic tumors: factors correlated with survival Original article Annals of Oncology 6: 86 8, 25 doi:.93/annonc/mdi358 Published online 5 August 25 Endocrine pancreatic tumors: factors correlated with survival P. Tomassetti *, D. Campana, L. Piscitelli,

More information

Medical Policy An independent licensee of the Blue Cross Blue Shield Association

Medical Policy An independent licensee of the Blue Cross Blue Shield Association Xermelo (telotristat) Page 1 of 5 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Xermelo (telotristat) Prime Therapeutics will review Prior Authorization requests

More information

Diabetes mellitus and its effects on all cause mortality after radiopeptide therapy for neuroendocrine tumors

Diabetes mellitus and its effects on all cause mortality after radiopeptide therapy for neuroendocrine tumors Journal of Nuclear Medicine, published on September 15, 2016 as doi:10.2967/jnumed.116.180687 Diabetes mellitus and its effects on all cause mortality after radiopeptide therapy for neuroendocrine tumors

More information

Somatostatin receptor agonists and antagonists Melpomeni Fani

Somatostatin receptor agonists and antagonists Melpomeni Fani Somatostatin receptor agonists and antagonists Melpomeni Fani Clinic of Radiology and Nuclear Medicine University of Basel Hospital, Switzerland Somatostatin and somatostatin receptors Human Somatostatin

More information

Surgical treatment and prognosis of gastrinoma

Surgical treatment and prognosis of gastrinoma Best Practice & Research Clinical Gastroenterology Vol. 19, No. 5, pp. 799 805, 2005 doi:10.1016/j.bpg.2005.05.003 available online at http://www.sciencedirect.com 10 Surgical treatment and prognosis of

More information

Use of Lanreotide (long acting Somatostatin analogue) in Congenital Hyperinsulinism (CHI)

Use of Lanreotide (long acting Somatostatin analogue) in Congenital Hyperinsulinism (CHI) Use of Lanreotide (long acting Somatostatin analogue) in Congenital Hyperinsulinism (CHI) Dr Pratik Shah Clinical Research fellow in Hyperinsulinism Clinical Molecular Genetics Unit Institute of Child

More information

Pembrolizumab for Patients With PD-L1 Positive Advanced Carcinoid or Pancreatic Neuroendocrine Tumors: Results From the KEYNOTE-028 Study

Pembrolizumab for Patients With PD-L1 Positive Advanced Carcinoid or Pancreatic Neuroendocrine Tumors: Results From the KEYNOTE-028 Study Pembrolizumab for Patients With PD-L1 Positive Advanced Carcinoid or Pancreatic Neuroendocrine Tumors: Results From the KEYNOTE-28 Study Abstract 427O Mehnert JM, Bergsland E, O Neil BH, Santoro A, Schellens

More information

Specialised Services Policy CP66: 68-gallium DOTA- peptide scanning for the Management of Neuroendocrine Tumours (NETs)

Specialised Services Policy CP66: 68-gallium DOTA- peptide scanning for the Management of Neuroendocrine Tumours (NETs) Specialised Services Policy CP66: Management of Neuroendocrine Tumours (NETs) Document Author: Assistant Planner for Cancer and Blood Executive Lead: Director of Quality and Nursing Approved by: Management

More information

Endocrine Tumors of the Gastrointestinal System. F. V. Nowak Ohio University March 22, 2005

Endocrine Tumors of the Gastrointestinal System. F. V. Nowak Ohio University March 22, 2005 Endocrine Tumors of the Gastrointestinal System F. V. Nowak Ohio University March 22, 2005 Gastroenteropancreatic Endocrine System Clear cells of endodermal origin found in the pancreas, stomach, small

More information

Somatuline Depot. Somatuline Depot (lanreotide) Description

Somatuline Depot. Somatuline Depot (lanreotide) Description Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.27 Subject: Somatuline Depot Page: 1 of 5 Last Review Date: December 8, 2017 Somatuline Depot Description

More information

The Antiproliferative Role of Lanreotide in Controlling Growth of Neuroendocrine Tumors: A Systematic Review

The Antiproliferative Role of Lanreotide in Controlling Growth of Neuroendocrine Tumors: A Systematic Review Gastrointestinal Cancer The Antiproliferative Role of Lanreotide in Controlling Growth of Neuroendocrine Tumors: A Systematic Review MICHAEL MICHAEL, a ROCIO GARCIA-CARBONERO, b MATTHIAS M. WEBER, c CATHERINE

More information

symposium article Gastrointestinal neuroendocrine tumors K. E. Öberg* introduction and epidemiology diagnosis symposium article biochemical markers

symposium article Gastrointestinal neuroendocrine tumors K. E. Öberg* introduction and epidemiology diagnosis symposium article biochemical markers 21 (Supplement 7): vii72 vii80, 2010 doi:10.1093/annonc/mdq290 Gastrointestinal neuroendocrine tumors K. E. Öberg* Department of Endocrine Oncology, University Hospital, SE-751 85 Uppsala, Sweden Gastrointestinal

More information

Management of Pancreatic Islet Cell Tumors

Management of Pancreatic Islet Cell Tumors Management of Pancreatic Islet Cell Tumors Ravi Dhanisetty, MD November 5, 2009 Morbidity and Mortality Conference Case Presentation 42 yr female with chronic abdominal pain. PMHx: Uterine fibroids Medications:

More information

NICaN Pancreatic Neuroendocrine Tumour SACT protocols. 1.0 Dr M Eatock Final version issued

NICaN Pancreatic Neuroendocrine Tumour SACT protocols. 1.0 Dr M Eatock Final version issued Reference No: Title: Author(s) Systemic Anti-Cancer Therapy (SACT) Guidelines for Pancreatic Neuro-endocrine Tumours Dr Martin Eatock, Consultant Medical Oncologist & on behalf of the GI Oncologists Group,

More information

Lu 177-Dotatate (Lutathera) Therapy Information

Lu 177-Dotatate (Lutathera) Therapy Information Lu 177-Dotatate (Lutathera) Therapy Information Information for Lu 177-dotatate therapy also known as Lutathera, for the treatment of metastatic midgut neuroendocrine tumor and other metastatic neuroendocrine

More information

NET εντέρου Τι νεότερο/ Νέες μελέτες. Μαντώ Νικολαΐδη παθολόγος-ογκολόγος ΜΗΤΕΡΑ

NET εντέρου Τι νεότερο/ Νέες μελέτες. Μαντώ Νικολαΐδη παθολόγος-ογκολόγος ΜΗΤΕΡΑ NET εντέρου Τι νεότερο/ Νέες μελέτες Μαντώ Νικολαΐδη παθολόγος-ογκολόγος ΜΗΤΕΡΑ NET: A Diverse Group of Malignancies 1-3 Wide spectrum of malignancies arising in neuroendocrine cells throughout the body

More information

Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors

Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors REVIEW Endocrine-Related Cancer (2010) 17 R53 R73 Somatostatin receptor-based imaging and therapy of gastroenteropancreatic neuroendocrine tumors Dik J Kwekkeboom 1, Boen L Kam 1, Martijn van Essen 1,

More information

Original article. M. Cimitan 1 *, A. Buonadonna 2, R. Cannizzaro 3, V. Canzonieri 4, E. Borsatti 1, R. Ruffo 1 & L. De Apollonia 5.

Original article. M. Cimitan 1 *, A. Buonadonna 2, R. Cannizzaro 3, V. Canzonieri 4, E. Borsatti 1, R. Ruffo 1 & L. De Apollonia 5. Original article Annals of Oncology 14: 1135 1141, 2003 DOI: 10.1093/annonc/mdg279 Somatostatin receptor scintigraphy versus chromogranin A assay in the management of patients with neuroendocrine tumors

More information

Surgical treatment of neuroendocrine metastases

Surgical treatment of neuroendocrine metastases Best Practice & Research Clinical Gastroenterology Vol. 19, No. 4, pp. 577 583, 2005 doi:10.1016/j.bpg.2005.04.003 available online at http://www.sciencedirect.com 6 Surgical treatment of neuroendocrine

More information

AN ARGUMENT FOR SURGERY FOR GASTRINOMA. Lauren Wilson R1 General Surgery

AN ARGUMENT FOR SURGERY FOR GASTRINOMA. Lauren Wilson R1 General Surgery AN ARGUMENT FOR SURGERY FOR GASTRINOMA Lauren Wilson R1 General Surgery WHAT IS A GASTRINOMA? Gastrin secreting cells derived from multipotential stem cells of endodermal origin or enteroendocrine cells

More information

UnitedHealthcare Pharmacy Clinical Pharmacy Programs

UnitedHealthcare Pharmacy Clinical Pharmacy Programs UnitedHealthcare Pharmacy Clinical Pharmacy Programs Program Number 2018 P 1091-7 Program Prior Authorization/Notification Medication Sandostatin (octreotide acetate) Note: Only the subcutaneous formulation

More information

NIH Public Access Author Manuscript Pancreas. Author manuscript; available in PMC 2009 July 1.

NIH Public Access Author Manuscript Pancreas. Author manuscript; available in PMC 2009 July 1. NIH Public Access Author Manuscript Published in final edited form as: Pancreas. 2008 July ; 37(1): 94 100. doi:10.1097/mpa.0b013e31816907ab. Clinical Value of Monitoring Plasma Octreotide Levels During

More information

Managing Acromegaly: Biochemical Control with SIGNIFOR LAR (pasireotide)

Managing Acromegaly: Biochemical Control with SIGNIFOR LAR (pasireotide) Managing Acromegaly: Biochemical Control with SIGNIFOR LAR (pasireotide) INDICATION AND USAGE SIGNIFOR LAR (pasireotide) for injectable suspension is a somatostatin analog indicated for the treatment of

More information

PACKAGE LEAFLET TEXT ZOLADEX LA 10.8MG. (goserelin)

PACKAGE LEAFLET TEXT ZOLADEX LA 10.8MG. (goserelin) ONC.000-092-861.10.0 PACKAGE LEAFLET TEXT ZOLADEX LA 10.8MG (goserelin) Name of the medicinal product Zoladex LA 10.8mg depot Qualitative and quantitative composition Goserelin acetate (equivalent to 10.8

More information

Nuclear oncology using SPECT and PET is able to show

Nuclear oncology using SPECT and PET is able to show Molecular Imaging as In Vivo Molecular Pathology for Gastroenteropancreatic Neuroendocrine Tumors: Implications for Follow-Up After Therapy Eric P. Krenning, MD, PhD 1,2 ; Roelf Valkema, MD, PhD 1 ; Dik

More information

Strategies in the Management of Neuroendocrine Tumors. Dr. Jean Maroun Dr. Elena Tsvetkova

Strategies in the Management of Neuroendocrine Tumors. Dr. Jean Maroun Dr. Elena Tsvetkova Strategies in the Management of Neuroendocrine Tumors Dr. Jean Maroun Dr. Elena Tsvetkova 1 A ZORSE 2 Neuroendocrine Tumour Classification Neuroendocrine Tumours Carcinoid Tumours Pancreatic Neuroendocrine

More information

Cutting Edge Treatment of Neuroendocrine Tumors

Cutting Edge Treatment of Neuroendocrine Tumors Cutting Edge Treatment of Neuroendocrine Tumors Daneng Li, MD Assistant Clinical Professor Department of Medical Oncology & Therapeutics Research City of Hope Click to edit Master Presentation Date DISCLOSURE

More information

Cutting Edge Treatment of Neuroendocrine Tumors

Cutting Edge Treatment of Neuroendocrine Tumors Cutting Edge Treatment of Neuroendocrine Tumors Daneng Li, MD Assistant Clinical Professor Department of Medical Oncology & Therapeutics Research City of Hope Click to edit Master Presentation Date DISCLOSURE

More information

SSTR2A Protein Expression in Neuroendocrine Neoplasms of the Colorectum

SSTR2A Protein Expression in Neuroendocrine Neoplasms of the Colorectum The Korean Journal of Pathology 2011; 45: 276-280 DOI: 10.4132/KoreanJPathol.2011.45.3.276 SSTR2A Protein Expression in Neuroendocrine Neoplasms of the Colorectum Young Eun Kim Jeeyun Lee 1 Young Suk Park

More information

Practical Strategies for the Clinical Use of Incretin Mimetics CME/CE. CME/CE Released: 09/15/2009; Valid for credit through 09/15/2010

Practical Strategies for the Clinical Use of Incretin Mimetics CME/CE. CME/CE Released: 09/15/2009; Valid for credit through 09/15/2010 Practical Strategies for the Clinical Use of Incretin Mimetics CME/CE Robert R. Henry, MD Authors and Disclosures CME/CE Released: 09/15/2009; Valid for credit through 09/15/2010 Introduction Type 2 diabetes

More information

TUMORES NEUROENDOCRINOS. Miguel Navarro. Salamanca

TUMORES NEUROENDOCRINOS. Miguel Navarro. Salamanca TUMORES NEUROENDOCRINOS Miguel Navarro. Salamanca Introduction to Neuroendocrine Tumours (NETs) NETs are relatively RARE At least 40 different entities are described arising in different organs. Different

More information

A case of persistent diarrhoea. Dr. Miles Levy, Dr. Jenny Prouten, Priya Jalota

A case of persistent diarrhoea. Dr. Miles Levy, Dr. Jenny Prouten, Priya Jalota A case of persistent diarrhoea Dr. Miles Levy, Dr. Jenny Prouten, Priya Jalota Presentation 58 year old male with 3/12 history of persistent change in bowel habit following trip to India in January 2012

More information

NET ΠΝΕΥΜΟΝΑ: τι νεότερο / νέες μελέτες

NET ΠΝΕΥΜΟΝΑ: τι νεότερο / νέες μελέτες NETMASTERCLASS 2017: an interactive workshop NET ΠΝΕΥΜΟΝΑ: τι νεότερο / νέες μελέτες Νικόλαος Τσουκαλάς MD, MSc, PhD Ογκολόγος - Παθολόγος, MSc Βιοπληροφορική Επιμελητής Α, Ογκολογικό Τμήμα Νοσηλευτικό

More information

Systemic Therapy for Pheos/Paras: Somatostatin analogues, small molecules, immunotherapy and other novel approaches in the works.

Systemic Therapy for Pheos/Paras: Somatostatin analogues, small molecules, immunotherapy and other novel approaches in the works. Systemic Therapy for Pheos/Paras: Somatostatin analogues, small molecules, immunotherapy and other novel approaches in the works. Arturo Loaiza-Bonilla, MD, FACP Assistant Professor of Clinical Medicine

More information

Hypothalamic & Pituitary Hormones

Hypothalamic & Pituitary Hormones 1 Hypothalamic & Pituitary Hormones Pharmacologic Applications: Drugs that mimic or block the effects of hypothalamic or pituitary hormones have the following applications: 1. Replacement therapy for hormone

More information

Updates in Pancreatic Neuroendocrine Carcinoma Highlights from the 2010 ASCO Annual Meeting. Chicago, IL, USA. June 4-8, 2010

Updates in Pancreatic Neuroendocrine Carcinoma Highlights from the 2010 ASCO Annual Meeting. Chicago, IL, USA. June 4-8, 2010 HIGHLIGHT ARTICLE Updates in Pancreatic Neuroendocrine Carcinoma Highlights from the 2010 ASCO Annual Meeting. Chicago, IL, USA. June 4-8, 2010 Susan Alsamarai 1, Steven K Libutti 2, Muhammad Wasif Saif

More information

Prior Authorization Review Panel MCO Policy Submission

Prior Authorization Review Panel MCO Policy Submission Prior Authorization Review Panel MCO Policy Submission A separate copy of this form must accompany each policy submitted for review. Policies submitted without this form will not be considered for review.

More information

QOL Improvements in NETTER-1 Phase III Trial in Patients With Progressive Midgut Neuroendocrine Tumors

QOL Improvements in NETTER-1 Phase III Trial in Patients With Progressive Midgut Neuroendocrine Tumors QOL Improvements in NETTER-1 Phase III Trial in Patients With Progressive Midgut Neuroendocrine Tumors Abstract C-33 Strosberg J, Wolin E, Chasen B, Kulke M, Bushnell D, Caplin M, Baum RP, Kunz P, Hobday

More information

See Important Reminder at the end of this policy for important regulatory and legal information.

See Important Reminder at the end of this policy for important regulatory and legal information. Clinical Policy: (Sandostatin, Sandostatin LAR Depot) Reference Number: CP.PHAR.40 Effective Date: 03.01.10 Last Review Date: 02.18 Line of Business: Commercial, Medicaid Coding Implications Revision Log

More information

Effective treatment of bone metastases from a neuroendocrine tumour of the pancreas with high activities of Indium-111-pentetreotide

Effective treatment of bone metastases from a neuroendocrine tumour of the pancreas with high activities of Indium-111-pentetreotide European Journal of Endocrinology (2003) 149 479 483 ISSN 0804-4643 CASE REPORT Effective treatment of bone metastases from a neuroendocrine tumour of the pancreas with high activities of Indium-111-pentetreotide

More information

Systemic Therapy for Advanced Pancreatic Neuroendocrine Tumors: An Update

Systemic Therapy for Advanced Pancreatic Neuroendocrine Tumors: An Update Focused Review 777 Systemic Therapy for Advanced Pancreatic Neuroendocrine Tumors: An Update Diane L. Reidy-Lagunes, MD, MS Abstract Well-differentiated neuroendocrine tumors (NETs) can be subdivided into

More information

Comprehensive treatment of a functional pancreatic neuroendocrine tumor with multifocal liver metastases

Comprehensive treatment of a functional pancreatic neuroendocrine tumor with multifocal liver metastases Case Report Comprehensive treatment of a functional pancreatic neuroendocrine tumor with multifocal liver metastases Wei Wang 1,2,3 *, Sharvesh Raj Seeruttun 1,2,3 *, Cheng Fang 1,2,3, Zhiwei Zhou 1,2,3

More information

FRANKLY SPEAKING ABOUT CANCER: NEUROENDOCRINE & CARCINOID TUMORS (NETS)

FRANKLY SPEAKING ABOUT CANCER: NEUROENDOCRINE & CARCINOID TUMORS (NETS) FRANKLY SPEAKING ABOUT CANCER: NEUROENDOCRINE & CARCINOID TUMORS (NETS) Gilda s Club Quad Cities November 5 th, 2018 Joseph Dillon, MD Neuroendocrine Tumor Clinic University of Iowa Hospitals & Clinics

More information

Hypoglycemia in congenital hyperinsulinism

Hypoglycemia in congenital hyperinsulinism How a normal body works: Our body is constantly at work. Our cells need a source of energy, and this source of energy is called glucose. The process is quite simple; think of it like an assembly line.

More information

Pancreatic polypeptide secreting tumors an institutional experience and review of the literature

Pancreatic polypeptide secreting tumors an institutional experience and review of the literature ORIGINAL ARTICLE Pancreatic polypeptide secreting tumors an institutional experience and review of the literature Angela Tatiana Alistar 1, Michelle Kang Kim 2, Richard Warner 2, Erin Moshier 3, Randall

More information

Clinical Value of Monitoring Plasma Octreotide Levels During Chronic Octreotide Long-Acting Repeatable Therapy in Carcinoid Patients

Clinical Value of Monitoring Plasma Octreotide Levels During Chronic Octreotide Long-Acting Repeatable Therapy in Carcinoid Patients ORIGINAL ARTICLE Clinical Value of Monitoring Plasma Octreotide Levels During Chronic Octreotide Long-Acting Repeatable Therapy in Carcinoid Patients Eugene A. Woltering, MD, FACS,* Vergilio A. Salvo,

More information

Small-cell lung cancer (SCLC) accounts for 15% to 18% of

Small-cell lung cancer (SCLC) accounts for 15% to 18% of BRIEF REPORT Brief Report on the Use of Radiolabeled Somatostatin Analogs for the Diagnosis and Treatment of Metastatic Small-Cell Lung Cancer Patients Martina Sollini, MD,* Daniela Farioli, MS,* Armando

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION Supplementary Table 1. Therapies for non-men1 pancreatic neuroendocrine tumours (NETs) (published after 2011) Somatostatin analogues Tumour type a Intervention Number of participants/information available

More information

Color Codes Pathology and Genetics Medicine and Clinical Pathology Surgery Imaging

Color Codes Pathology and Genetics Medicine and Clinical Pathology Surgery Imaging Saturday, November 5, 2005 8:30-10:30 a. m. Poorly Differentiated Endocrine Carcinomas Chairman: E. Van Cutsem, Leuven, Belgium 9:00-9:30 a. m. Working Group Sessions Pathology and Genetics Group leaders:

More information

NEUROENDOCRINE CARCINOID TUMORS PANCREATIC NEUROENDOCRINE TUMORS

NEUROENDOCRINE CARCINOID TUMORS PANCREATIC NEUROENDOCRINE TUMORS University of Miami Jackson Memorial Hospital Role of the Surgeon in the Approach to Neuroendocrine tumors Dido Franceschi, MD Professor of Surgery University of Miami Karzinoide Siegfried Oberndorfer,

More information

Edward M. Wolin Ke Hu Gareth Hughes Emmanuel Bouillaud Vanessa Giannone Karina Hermosillo Resendiz

Edward M. Wolin Ke Hu Gareth Hughes Emmanuel Bouillaud Vanessa Giannone Karina Hermosillo Resendiz Cancer Chemother Pharmacol (2013) 72:387 395 DOI 10.1007/s00280-013-2202-1 ORIGINAL ARTICLE Safety, tolerability, pharmacokinetics, and pharmacodynamics of a long-acting release (LAR) formulation of pasireotide

More information

NET und NEC. Endoscopic and oncologic therapy

NET und NEC. Endoscopic and oncologic therapy NET und NEC Endoscopic and oncologic therapy Classification well-differentiated NET - G1 and G2 - carcinoid poorly-differentiated NEC - G3 - like SCLC well differentiated NET G3 -> elevated proliferation

More information

Case Report Long-Term Survival of a Patient with Jejunal Somatostatin-Producing Tumour and Liver Metastases

Case Report Long-Term Survival of a Patient with Jejunal Somatostatin-Producing Tumour and Liver Metastases IBIMA Publishing International Journal of Case Reports in Medicine http://www.ibimapublishing.com/journals/ijcrm/ijcrm.html Vol. 2014 (2014), Article ID 421263, 6 pages DOI: 10.5171/2014.421263 Case Report

More information

Peptide Receptor Radio-Nuclide Therapy (PRRNT) as a Novel, Rationale Option of Care for Metastatic NETs

Peptide Receptor Radio-Nuclide Therapy (PRRNT) as a Novel, Rationale Option of Care for Metastatic NETs Peptide Receptor Radio-Nuclide Therapy (PRRNT) as a Novel, Rationale Option of Care for Metastatic NETs Presented by Thomas M. O Dorisio, M.D. Professor of Medicine Director, Carcinoid & Neuroendocrine

More information