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Background Treatment recommendations for patients with neuroendocrine tumors (NETs) include the use of octreotide long-acting release (LAR) for long-term therapy and immediate-release (IR) as rescue therapy to control the breakthrough symptoms of carcinoid syndrome (CS). High doses of LAR are commonly used in clinical practice. This study aimed to evaluate the real-world utilization of LAR and preceding IR use at the prescription and patient levels. Methods We used an administrative claims database (2009-2018) containing privately insured enrollees. We calculated the normalized LAR dose from pharmacy claims and the initial mean IR daily dose at the prescription level. At the patient level, we conducted a retrospective cohort study that included patients continuously enrolled with ≥1 pharmacy claim of LAR and evaluated the frequency and the clinical reason for dose escalation of LAR. The definition of the above-label maximum dose of LAR was ≥30 mg/4 weeks. Results Nineteen percent of LAR prescriptions had an above-label maximum dose. Only 7% of LAR prescriptions had preceding IR use. There were 386 patients with NETs or CS vs. 570 with an unknown diagnosis. Comparing patients with NETs or CS to those with an unknown diagnosis, 22.3% vs. 11.0 % experienced dose escalations and 29.0% vs. 26.6% had IR use before dose escalation, respectively. LAR dose escalation occurred in 50.9% vs. 39.2% for symptom control, 12.3% vs. 7.1% for tumor progression control, and 16.6% vs. 6.0% for both reasons in NETs/CS and unknown groups, respectively. Conclusion Octreotide LAR dosing above the label-maximum dose is common and IR rescue dosing appears to be underutilized. [ABSTRACT FROM AUTHOR]

Background: Somatostatin analogs (SSAs) are the frontline antitumor therapy in advanced well‐differentiated gastroenteropancreatic neuroendocrine tumors (GEP‐NETs). A subset of patients demonstrate early disease progression on SSA therapy, yet the currently known predictors for treatment failure lack specificity to affect therapeutic decision. SSAs target tumor somatostatin receptors, the level of which can be quantitatively assessed with 68Ga‐DOTATATE positron emission tomography‐computed tomography (PET/CT). We investigated the ability of 68Ga‐DOTATATE PET/CT to predict response to SSA therapy. Materials and Methods: The records of 108 consecutive patients with well‐differentiated grade 1–2 GEP‐NETs on SSA monotherapy who received 68Ga‐DOTATATE PET/CT scans were retrospectively reviewed to obtain baseline characteristics, 68Ga‐DOTATATE maximum standardized uptake value (SUVmax), and progression‐free survival (PFS) data. The optimal SUVmax cutoff for patient stratification was obtained with receiver operating characteristic curve analysis. PFS in the high versus low SUVmax groups was compared with Kaplan‐Meier survival analysis. The effects of baseline characteristics and SUVmax on PFS were examined with univariate and multivariate Cox regression. Results: 68Ga‐DOTATATE SUVmax predicted therapeutic failure with sensitivity and specificity of 39% and 98%, respectively. SUVmax of <18.35 was associated with shorter PFS, which was reproduced in the subgroup analysis of SSA‐naïve patients. Low SUVmax was the only predictor of early treatment failure (hazard ratio, 6.85) in multivariate analysis, as well as in the subgroup analysis of grade 2 GEP‐NETs. Conclusion: Low SUVmax on 68Ga‐DOTATATE PET/CT independently predicts early failure on SSA monotherapy in patients with well‐differentiated grade 1–2 GEP‐NET. Patients with lack of expected benefit from SSA therapy can be readily identified using routine 68Ga‐DOTATATE PET/CT with very high specificity. Implications for Practice: Based on 68Ga‐DOTATATE positron emission tomography‐computed tomography imaging, clinicians can better inform patients on the expected benefit of somatostatin analog therapy for gastroenteropancreatic neuroendocrine tumors, especially when access to the therapy is difficult, and offer proactive discussion on alternative management options. Somatostatin analogs (SSAs) are the frontline antitumor therapy for patients with advanced well‐differentiated gastroenteropancreatic neuroendocrine tumors. This study investigated the ability of 68Ga‐DOTATATE PET/CT to predict response to SSA therapy. [ABSTRACT FROM AUTHOR]

Spinal and bulbar muscular atrophy, also known as Kennedy’s disease, is an adult-onset hereditary neurodegenerative disorder caused by an expansion of the polyglutamine repeat in the first exon in the androgen receptor gene. Pathologically, the disease is defined by selective loss of spinal and bulbar motor neurons causing bulbar, facial and limb weakness. Although the precise disease pathophysiology is largely unknown, it appears to be related to abnormal accumulation of the pathogenic androgen receptor protein within the nucleus, leading to disruption of cellular processes. Using a mouse model of spinal and bulbar muscular atrophy that exhibits many of the characteristic features of the human disease, in vivo physiological assessment of muscle function revealed that mice with the pathogenic expansion of the androgen receptor develop a motor deficit characterized by a reduction in muscle force, abnormal muscle contractile characteristics, loss of functional motor units and motor neuron degeneration. We have previously shown that treatment with arimoclomol, a co-inducer of the heat shock stress response, delays disease progression in the mutant superoxide dismutase 1 mouse model of amyotrophic lateral sclerosis, a fatal motor neuron disease. We therefore evaluated the therapeutic potential of arimoclomol in mice with spinal and bulbar muscular atrophy. Arimoclomol was administered orally, in drinking water, from symptom onset and the effects established at 18 months of age, a late stage of disease. Arimoclomol significantly improved hindlimb muscle force and contractile characteristics, rescued motor units and, importantly, improved motor neuron survival and upregulated the expression of the vascular endothelial growth factor which possess neurotrophic activity. These results provide evidence that upregulation of the heat shock response by treatment with arimoclomol may have therapeutic potential in the treatment of spinal and bulbar muscular atrophy and may also be a possible approach for the treatment of other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]