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| 2. |
- Bushnell, David L., et al.
(författare)
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90Y-edotreotide for metastatic carcinoid refractory to octreotide
- 2010
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 28:10, s. 1652-1659
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Metastatic carcinoid is an incurable malignancy whose symptoms, such as diarrhea and flushing, can be debilitating and occasionally life-threatening. Although symptom relief is available with octreotide, the disease eventually becomes refractory to octreotide, leaving no proven treatment options. The goal of this study was to evaluate the clinical effect of using (90)Y-edotreotide to treat symptomatic patients with carcinoid tumors. PATIENTS AND METHODS: Patients enrolled had metastatic carcinoid, at least one sign/symptom refractory to octreotide, and at least one measurable lesion. Study treatment consisted of three cycles of 4.4 GBq (120 mCi) (90)Y-edotreotide each, once every 6 weeks. RESULTS: Ninety patients were enrolled in the study. Using Southwest Oncology Group tumor response criteria, 67 (74.%) of 90 patients (95% CI, 65.4% to 83.4%) were objectively stable or responded. A statistically significant linear trend toward improvement was demonstrated across all 12 symptoms assessed. Median progression-free survival was significantly greater (P = .03) for the 38 patients who had durable diarrhea improvement than the 18 patients who did not (18.2 v 7.9 months, respectively). Adverse events (AEs) were reported in 96.7% (87 of 90) of patients. These AEs consisted primarily of reversible GI events (76 of 90), which could be caused in part by concomitant administration of amino acid solution given to reduce radiation exposure to the kidneys. There was one case each of grade 3 oliguria and grade 4 renal failure, each lasting 6 days. CONCLUSION: (90)Y-edotreotide treatment improved symptoms associated with malignant carcinoid among subjects with no treatment alternatives. Treatment was well-tolerated and had an acceptable expected AE profile.
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| 3. |
- Grama, D, et al.
(författare)
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Clinical characteristics, treatment and survival of pancreatic tumors causing hormonal syndromes
- 1992
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Ingår i: World Journal of Surgery. - 0364-2313 .- 1432-2323. ; 16:4, s. 632-639
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Tidskriftsartikel (refereegranskat)abstract
- Eighty-five patients with endocrine pancreatic tumors associated with clinical syndromes of hormone excess were retrospectively analyzed regarding symptomatology, means of diagnosis, and results of surgical and medical treatment during follow-up of 3-18 years (median 8 years). The combination of angiography and computed tomography was most successful in pre-operative localization of both primary tumors and metastases. Surgery provided long term cure in 39 of 44 patients with benign islet cell lesions, the majority having insulinomas. Forty-one patients had malignant tumors, which at the time of diagnosis or operation were associated with liver and/or regional lymph gland metastases in 56% and 24%, respectively. Sixteen patients with metastatic disease and/or very large tumors were considered inoperable, 5 patients underwent palliative resection of their malignant tumors, while grossly radical tumor removal was accomplished in 20 patients. Long-term cure was achieved in 5 patients by excision of primary tumors and localized liver or lymph gland metastases. Half of the patients, particularly those with insulinoma, gastrinoma, or vipoma, showed response to streptozotocin, in combination with other cytostatics, for a median of 24 months or a response to interferon for a median of 10 months. The overall 5-year and 10-year survival among the patients with malignant islet cells tumors was 54% and 28%, respectively. Absence of liver metastases at time of operation/diagnosis, smaller size of the primary tumor, grossly radical tumor resection as well as response to medical therapy predicted the more favorable survival.
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| 4. |
- Grama, D, et al.
(författare)
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Pancreatic tumors in multiple endocrine neoplasia type 1 : clinical presentation and surgical treatment
- 1992
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Ingår i: World Journal of Surgery. - 0364-2313 .- 1432-2323. ; 16:4, s. 611-618
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Tidskriftsartikel (refereegranskat)abstract
- Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-term outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors.
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| 6. |
- Anthony, Lowell B., et al.
(författare)
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Impact of Previous Somatostatin Analogue Use on the Activity of Everolimus in Patients with Advanced Neuroendocrine Tumors : Analysis from the Phase III RADIANT-2 Trial
- 2015
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 102:1-2, s. 18-25
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: The phase III placebo-controlled RADI-ANT-2 trial investigated the efficacy of everolimus plus octreotide long-acting repeatable (LAR) in patients with advanced neuroendocrine tumors (NET) associated with carcinoid syndrome. Here we report a secondary analysis based on the previous somatostatin analogue (SSA) exposure status of patients enrolled in RADIANT-2. Methods: Patients were randomly assigned to receive oral everolimus 10 mg/day plus octreotide LAR 30 mg intramuscularly (i.m.) or to receive matching placebo plus octreotide LAR 30 mg i.m. every 28 days. SSA treatment before study enrollment was permitted. Patient characteristics and progression-free survival (PFS) were analyzed by treatment arm and previous SSA exposure status. Results: Of the 429 patients enrolled in RADI-ANT-2, 339 were previously exposed to SSA (95% received octreotide); 173 of 339 patients were in the everolimus plus octreotide LAR arm. All patients had a protocol-specified history of secretory symptoms, but analysis by type showed that more patients who previously received SSA therapy had a history of flushing symptoms (77%), diarrhea (86%), or both (63%) compared with SSA-naive patients (62, 62, and 24%, respectively). Patients who received everolimus plus octreotide LAR had longer median PFS regardless of previous SSA exposure (with: PFS 14.3 months, 95% confidence interval, CI, 12.0-20.1; without: 25.2 months, 95% CI, 12.0-not reached) compared with patients who received placebo plus octreotide LAR (with: 11.1 months, 95% CI, 8.4-14.6; without: 13.6 months, 95% CI, 8.2-22.7). Conclusion: Everolimus in combination with octreotide improves PFS in patients with advanced NET associated with carcinoid syndrome, regardless of previous SSA exposure.
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| 7. |
- Anthony, Lowell B., et al.
(författare)
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Long-Term Safety Experience with Telotristat Ethyl Across Five Clinical Studies in Patients with Carcinoid Syndrome
- 2019
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Ingår i: The Oncologist. - : WILEY. - 1083-7159 .- 1549-490X. ; 24:8, s. E662-E670
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience considerable morbidity and mortality; carcinoid syndrome may be associated with shorter survival. Carcinoid syndrome is linked to tumoral secretion of serotonin and other bioactive substances. The subsequent debilitating diarrhea and urgency to defecate pose significant health risks. In previous studies, telotristat ethyl, a tryptophan hydroxylase inhibitor, was effective and well tolerated in treating carcinoid syndrome diarrhea. We present pooled safety data from five clinical trials with telotristat ethyl in patients with carcinoid syndrome. Subjects, Materials, and Methods Adverse events reported during telotristat ethyl treatment were pooled from two phase II and three phase III clinical trials in 239 patients with carcinoid syndrome. Long-term safety of telotristat ethyl and causes of hospitalization and death were reviewed; overall survival was estimated. Results Mean (median; range) duration of exposure and follow-up was 1.3 years (1.1 years; 1 week to 5.7 years), with 309 total patient-years of exposure. Leading causes of hospitalization were gastrointestinal disorders or were related to the underlying tumor and related treatment. Survival estimates at 1, 2, and 3 years were 93%, 88%, and 77%. Nearly all deaths were due to progression or complication of the underlying disease; none were attributable to telotristat ethyl. There was one death in year 4. Conclusion Based on long-term safety data, telotristat ethyl is well tolerated and has a favorable long-term safety profile in patients with carcinoid syndrome. Implications for Practice Carcinoid syndrome can cause persistent diarrhea, even in patients treated with somatostatin analogs. Across five clinical trials in patients with carcinoid syndrome, telotristat ethyl has been well tolerated and efficacious, providing clinicians with a new approach to help control carcinoid syndrome diarrhea, in addition to somatostatin analog therapy. By reducing the stool frequency in patients with carcinoid syndrome whose diarrhea is refractory to anticholinergics, such as loperamide and atropine/diphenoxylate, and somatostatin analog dose escalation, improvement in quality of life becomes an achievable goal.
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| 8. |
- Anthony, Lowell, et al.
(författare)
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Understanding the Patient Experience with Carcinoid Syndrome : Exit Interviews from a Randomized, Placebo-controlled Study of Telotristat Ethyl
- 2017
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Ingår i: Clinical Therapeutics. - : Elsevier. - 0149-2918 .- 1879-114X. ; 39:11, s. 2158-2168
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Telotristat ethyl, an oral tryptophan hydroxylase inhibitor, is intended to treat carcinoid syndrome by reducing serotonin production. Telotristat ethyl was evaluated in FELESTAR, a Phase HI study for patients who had carcinoid syndrome with at least 4 bowel movements (BMs) per day and who were receiving somatostatin analogue therapy. This interview sub study was conducted to provide insight into the patient experience in ILLESTAR and to help understand whether reductions in BM frequency (the primary end point) and other symptoms were clinically meaningful. Methods: Participating sites were asked to invite (before randomization) all eligible patients to telephone interviews scheduled at the end of the double-blind treatment period. Patients and interviewers were blinded to treatment. Findings: All 35 interviewed participants reported diarrhea and/or excessive BMs at baseline. Patients reported that these symptoms negatively affected emotional, social, physical, and occupational well-being. Prespecified criteria for treatment response (achieving >= 30% reduction in BM frequency for at least 50% of the days) were met by 8 of 26 patients taking telotristat ethyl and 1 of 9 patients taking placebo. All 8 patients taking telotristat ethyl described clinically meaningful reductions in BM frequency and were very satisfied with the ability of the study drug to control their carcinoidsyndrome symptoms. Overall, reports of being very satisfied were observed in 12 patients taking telotristat ethyl and 0 taking placebo. Implications: Patient interviews revealed that I ELESTAR patients, at baseline, were significantly affected by their high BM frequency. Patient reports of their clinical trial experience supported the significance of the primary end point and clinical responder analysis in TELESTAR, helping identify and understand clinically meaningful change produced by telotristat ethyl. (C) 2017 The Authors. Published by Elsevier HS Journals, Inc.
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| 10. |
- Eriksson, B, et al.
(författare)
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[PET in neuroendocrine tumors].
- 1998
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Ingår i: Nordisk Medicin. - 0029-1420. ; 113:9, s. 308-312
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Tidskriftsartikel (refereegranskat)abstract
- With the radionuclide tracers available today, 50-90 per cent of neuroendocrine tumours of the gastro-intestinal tract can be visualised with PET (positron-emission tomography). PET also enables the effect of tumour treatment to be monitored in terms of biochemical and functional variables, which is not possible with other radiological techniques. Owing to the very good tumour resolution possible with PET, it serves as a complement to other routine methods such as computed tomography and ultrasonography, and can be used to screen the chest and abdomen for small primary tumours that can not be detected with other methods. In several pre-operative trials PET has been shown to demonstrate more changes in the pancreas and liver than was possible with other methods. In the near future it will be possible to demonstrate the presence of and quantify growth factor receptors, hormones, enzymes, DNA synthesis, mRNA synthesis and protein synthesis. Access to these tumour biological data will be of crucial importance to the individualisation of treatment.
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