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Everolimus and peptide receptor radionuclide therapy (PRRT, 177 Lu-DOTATATE) are 2 treatments recommended in guidelines for gastroenteropancreatic metastatic neuroendocrine tumors. However, the best treatment sequence remains unknown. Methods: We designed a retrospective multicenter study that included patients from the national prospective database of the Groupe d'Étude des Tumeurs Endocrines who had been treated using everolimus and PRRT between April 2004 and October 2022. The primary aim was to compare the 2 treatments (everolimus and PRRT) in terms of efficacy and safety, and the secondary aim was to evaluate the sequences (PRRT followed by everolimus or everolimus followed by PRRT) based on overall progression-free survival (PFS) (PFS during first treatment + PFS during second treatment) in patients with metastatic neuroendocrine tumors. Results: Both treatments were used for 84 patients. The objective response rate and median PFS were 5 (6.0%) and 16.1 mo (95% CI, 11.5-20.7 mo), respectively, under everolimus and 19 (22.6%) and 24.5 mo (95% CI, 17.7-31.3 mo), respectively, for PRRT. The safety profile was also better for PRRT. Median overall PFS was 43.2 mo (95% CI, 33.7-52.7 mo) for the everolimus-PRRT sequence and 30.6 mo (95% CI, 17.8-43.4 mo) for the PRRT-everolimus sequence (hazard ratio, 0.69; 95% CI, 0.39-1.24; P = 0.22). Conclusion: PRRT was more effective and less toxic than everolimus. Overall PFS was similar between the 2 sequences, suggesting case-by-case discussion if the patient is eligible for both treatments, but PRRT should be used first when an objective response is needed or in frail populations., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objective: Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF rates in patients randomized between somatostatin versus octreotide as prophylactic treatment., Methods: Multicentric randomized controlled open study in patient's candidate for pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) comparing somatostatin continuous intravenous infusion for 7 days versus octreotid 100 μg, every 8 hours subcutaneous injection for 7 days, stratified by procedure (PD vs DP) and size of the main pancreatic duct (>4 mm) on grade B/C POPF rates at 90 days based on an intention-to-treat analysis., Results: Of 763 eligible patients, 651 were randomized: 327 in the octreotide arm and 324 in the somatostatin arm, with comparable the stratification criteria - type of surgery and main pancreatic duct dilatation. Most patients had PD (n=480; 73.8%), on soft/normal pancreas (n=367; 63.2%) with a nondilated main pancreatic duct (n=472; 72.5%), most often for pancreatic adenocarcinoma (n=311; 47.8%). Almost all patients had abdominal drainage (n=621; 96.1%) and 121 (19.5%) left the hospital with the drain in place (median length of stay=16 days). A total of 153 patients (23.5%) developed a grade B/C POPF with no difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ 2 test, P =0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis., Conclusion: Continuous intravenous somatostatin is not statistically different from subcutaneous octreotide in the prevention of grade B/C POPF after pancreatectomy., Findings: In the PREFIPS Randomized Clinical Trial including 651 patients, a total of 153 patients (23.5%) developed a grade B/C POPF with no significant difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ 2 test, P =0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis., Competing Interests: S.G. reported grants, personal fees, and nonfinancial support fomr IPSEN, Mylan, Mayoli, Novartis. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The first long-acting release (LAR) formulation of octreotide was marketed in France in the late 1990s. An injectable formulation of Sandostatin LAR ® (Novartis SAS) with a new diluent has been developed to facilitate its preparation and administration and to improve its use in practice., Methods: We conducted an observational, cross-sectional and multicenter study in France whose main outcome was to compare nurses' satisfaction with the preparation and administration of both previous and new formulations of octreotide LAR. Secondary outcomes included assessment of patient satisfaction (quality of life and pain felt during the injection) and product tolerance. Data were collected at two time points (one for the first formulation group and one for the second formulation group) through paper questionnaires administered to physicians, patients and nurses including a visual analog scale (VAS) from 0 (unsatisfied) to 10 (very satisfied)., Results: Results showed that overall nurse satisfaction improved from 5.3 (95% CI 4.9-5.8) with the previous formulation to 7.5 (95% CI 7-7.9) with the new formulation (p < 0.0001). Regarding secondary outcomes, the simplicity of the injection increased (84% for the previous formulation and 94% for the new formulation) and the purge problem disappeared (36% for the previous formulation and 4% for the new formulation)., Conclusion: The improvement due to the new formulation of Sandostatin LAR ® was reported in terms of handling, ease of use and overall nurse satisfaction. The new formulation greatly reduced treatment administration problems associated with the previous formulation, while maintaining low injection site pain and an equivalent safety profile in both indications.

Neuroendocrine tumors (NET) represent a heterogeneous group of tumors originating from cells of neuroendocrine origin, which express somatostatin receptors (SSTR). This property allowed the successful development of radionuclides for diagnostic and peptide radionuclide radiation therapy (PRRT). This is the paradigm for the theragnostic concept in NET personalized medicine. The only phase III study to date (NETTER-1) clearly demonstrated the ability of 177 Lutetium-based PRRT to improve progression-free survival in advanced intestinal NETs. In clinical practice, the indications are limited to G1-G2 well-differentiated NETs with high expression of SSTR. NETs with a low tumor burden and slow progression are probably the optimal indication. This treatment is now available in France. However, its precise position in the treatment algorithm remains to be explored. We provide an overview of receptor radionuclide utilization and mechanism in diagnostic and pretherapeutic imaging and we focus on PRRT for endocrine tumors., (Copyright © 2019. Published by Elsevier Masson SAS.)

This phase II, multicenter, randomized, double-blind, non-comparative study assessed the efficacy and safety of immediate-release octreotide and octreotide LAR, in combination with corticosteroids and standard medical care, on the symptoms of inoperable malignant bowel obstruction (MBO) due to peritoneal carcinomatosis. The primary efficacy endpoint was "success" at day 14 defined as a composite endpoint including the absence of a nasogastric tube, and vomiting less than twice per day and no use of anticholinergic agents. Patients in the octreotide arm received octreotide LAR 30 mg intramuscular (im) on days 1, 29 and 57, as well as daily immediate-release octreotide 600 μg per day plus methylprednisolone on days 1 to 6. Placebo-treated patients received methylprednisolone and matched placebo instead of octreotide. Difficulties associated with enrolling patients at palliative-care stage meant only 64 patients (instead of the planned 102 patients) were randomized, 32 to octreotide and 32 to placebo. Despite randomization, more patients in the octreotide arm (46.4%) than in the placebo arm (21.9%) had a baseline Karnofsky score less than 50. An intention-to-treat analysis showed that in the octreotide and placebo arms, 12 (38%) and nine (28%), respectively, patients were successfully treated at day 14, which increased to 9/15 (60%) and 7/25 (28%), respectively, among patients with a baseline Karnofsky score greater or equal to 50. Octreotide-treated patients reported three drug-related adverse events (AEs), and no drug-related serious AEs or deaths. Octreotide LAR may have a key role in treating patients with a MBO due to peritoneal carcinomatosis, particularly in those with moderately severe disease.

Morbidity and mortality in endocrine gastro-enteropancreatic (GEP) tumours are mainly related to the clinical consequences of tumoral peptide hypersecretion. Surgical resection at an early stage is the only curative treatment. However, most tumours are detected only when the hypersecretory state reflects the presence of metastases; surgery and chemotherapy then give only palliative results counterbalanced by serious side-effects. Somatostatin inhibits most endocrine secretions of the GEP tract and thus can alleviate invalidating symptoms. Its use is limited by its short half-life (2 min), the necessity of i.v. infusion and the possibility of a rebound phenomenon. Octreotide, a synthetic somatostatin analogue with a long duration of action, is administered subcutaneously and allows ambulatory treatment. In our series of 78 patients we observed about 80 percent of excellent or good clinical results, enabling the patients to resume normal life. Only minor and transient side-effects were noted. The overall tolerance of the drug was considered excellent or good. Prolonged administration of octreotide is a safe and effective symptomatic treatment in patients without any restriction of anti-tumoral procedures. Furthermore, it prevents the severe carcinoid crises that occur during surgery or embolization in patients with carcinoid syndromes.

Twenty-two patients with moderate to severe carcinoid syndrome received Sandostatin in doses ranging from 50 to 500 micrograms b.i.d. subcutaneously in addition to their usual drug therapies. Symptoms were reported improved in 60% of patients following a test period of Sandostatin. Lack of effect was observed in 5 patients and a lethal complication (obstructing intestinal tumour) occurred in 1. Of 13 patients who received Sandostatin for 3-36 months, 9 remain under control; 3 patients died - 1 from carcinoid spread and the other 2 from unrelated causes. Side effects have been few and mild. In summary, Sandostatin is a valuable agent in the management of carcinoid syndrome.

The French Sandostatin/Acromegaly Study Group performed a multicentric, prospective, open-label trial of incremental doses with the aim of obtaining the best antisecretory effect. Forty-two patients (24 women, 18 men) aged 22-71 years were involved, either after unsuccessful surgery and/or radiotherapy (30 patients), or as primary treatment (12 patients). Doses were increased from 3 x 100 to 3 x 500 micrograms/day, according to the results of hormonal investigations (GH profiles and Sm-C) performed each month and for each dose, and tolerability. Four patients dropped out because of major digestive troubles. Recurrent pain at the injection site and minor gastrointestinal disorders were noted in some patients. Asymptomatic gallstones appeared in 4 patients. Carbohydrate tolerance and insulin secretion (determined by diurnal plasma glucose and insulin profiles) were not significantly altered by the various SMS doses. Clinical improvement was determined by the scoring of the symptoms. Mean plasma GH concentrations were significantly reduced for each SMS dose, compared to pretreatment values. Fifteen patients obtained 75% of GH values less than or equal to 2 micrograms/l. In 9 patients the highest dose failed to bring GH below 10 micrograms/l. Sm-C normalized in 17/31 patients. After 6 months of treatment a tumor reduction of 20-50% was found in 7 patients and greater than 50% in 5 patients. We conclude that (1) the tolerability of SMS is compatible with long-term treatments; (2) clinical improvement and biological criteria of efficacy are obtained in 3/4 acromegalic patients treated by SMS, and that (3) some patients are resistant to SMS and the increase in the dose does not improve the result.