Treatment escape reduces the effectiveness of cabergoline during long-term treatment of acromegaly in monotherapy or in association with first-generation somatostatin receptor ligands

2018 ◽  
Vol 88 (6) ◽  
pp. 889-895 ◽  
Author(s):  
Leandro Kasuki ◽  
Marilia Duarte Dalmolin ◽  
Luiz Eduardo Wildemberg ◽  
Mônica R. Gadelha
Keyword(s):  
First Generation ◽  
Somatostatin Receptor ◽  
Term Treatment ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Long Term Treatment

scholarly journals gsp Mutation Is Not a Molecular Biomarker of Long-Term Response to First-Generation Somatostatin Receptor Ligands in Acromegaly

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4857
Author(s):  
Luiz Eduardo Wildemberg ◽  
Daniel Henriques ◽  
Paula C. L. Elias ◽  
Carlos Henrique de A. Lima ◽  
Nina R. de Castro Musolino ◽  
...  
Keyword(s):  
First Generation ◽  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Biochemical Control ◽  
Molecular Biomarker ◽  
Α Subunit ◽  
Cavernous Sinus Invasion ◽  
Somatostatin Receptor Ligands ◽  
Term Response

Background: It is still controversial if activating mutations in the stimulatory G-protein α subunit (gsp mutation) are a biomarker of response to first generation somatostatin receptor ligands (fg-SRL) treatment in acromegaly. Thus, we aimed to evaluate whether gsp mutation predicts long-term response to fg-SRL treatment and to characterize the phenotype of patients harboring gsp mutations. Methods: GNAS1 sequencing was performed by Sanger. SST2 and SST5 were analyzed by immunohistochemistry (IHC) and real-time RT-PCR. The cytokeratin granulation pattern was evaluated by IHC. Biochemical control was defined as GH < 1.0 ng/mL and normal age-adjusted IGF-I levels. Results: gsp mutation was found in 54 out of 136 patients evaluated. Biochemical control with fg-SRL treatment was similar in gsp+ and gsp- patients (37% vs. 25%, p = 0.219). Tumors harboring gsp mutation were smaller (p = 0.035) and had a lower chance of invading cavernous sinuses (p = 0.001). SST5 protein (p = 0.047) and mRNA (p = 0.013) expression levels were higher in wild-type tumors. Conclusions: In this largest series available in the literature, we concluded that gsp is not a molecular biomarker of response to fg-SRL treatment in acromegaly. However, the importance of its negative association with cavernous sinus invasion and SST5 expression needs to be further investigated.

Do antiserotonergic antipsychotics induce OCD more frequently than first-generation antipsychotics in the long-term treatment of schizophrenia?

2005 ◽  
Vol 38 (05) ◽  
Author(s):  
X Schlenzig ◽  
J Rentzsch ◽  
SBD Bahri ◽  
H Danker-Hopfe ◽  
MC Jockers-Scherübl
Keyword(s):  
First Generation ◽  
Term Treatment ◽  
Long Term Treatment

MRI follow‐up of patients with acromegaly treated after surgery with first‐generation somatostatin receptor ligands

2021 ◽  
Author(s):  
Naia Grandgeorge ◽  
Giovanni Barchetti ◽  
Solange Grunenwald ◽  
Fabrice Bonneville ◽  
Philippe Caron
Keyword(s):  
First Generation ◽  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands

scholarly journals Treatment of Aggressive Pituitary Adenomas: A Case-Based Narrative Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Odelia Cooper ◽  
Vivien Bonert ◽  
Ning-Ai Liu ◽  
Adam N. Mamelak
Keyword(s):  
Radiation Therapy ◽  
Pituitary Adenomas ◽  
Somatostatin Receptor ◽  
Mtor Inhibitors ◽  
Disease Recurrence ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Individualized Approach ◽  
Evidence Based Guidelines

Management of aggressive pituitary adenomas is challenging due to a paucity of rigorous evidence supporting available treatment approaches. Recent guidelines emphasize the need to maximize standard therapies as well as the use of temozolomide and radiation therapy to treat disease recurrence. However, often these adenomas continue to progress over time, necessitating the use of additional targeted therapies which also impact quality of life and long-term outcomes. In this review, we present 9 cases of aggressive pituitary adenomas to illustrate the importance of a multidisciplinary, individualized approach. The timing and rationale for surgery, radiation therapy, temozolomide, somatostatin receptor ligands, and EGFR, VEGF, and mTOR inhibitors in each case are discussed within the context of evidence-based guidelines and clarify strategies for implementing an individualized approach in the management of these difficult-to-treat-adenomas.

scholarly journals The future of somatostatin receptor ligands in acromegaly

2021 ◽  
Author(s):  
Monica R Gadelha ◽  
Luiz Eduardo Wildemberg ◽  
Leandro Kasuki
Keyword(s):  
Precision Medicine ◽  
First Generation ◽  
Somatostatin Receptor ◽  
New Drugs ◽  
Response To Treatment ◽  
Tumor Shrinkage ◽  
Receptor Ligands ◽  
Biochemical Control ◽  
Somatostatin Receptor Ligands ◽  
The Future

Abstract Currently, first-generation somatostatin receptor ligands (fg-SRLs), octreotide LAR and lanreotide autogel, are the mainstays of acromegaly treatment and achieve biochemical control in approximately 40% of patients and tumor shrinkage in over 60% of patients. Pasireotide, a second-generation SRL, shows higher efficacy with respect to both biochemical control and tumor shrinkage but has a worse safety profile. In this review, we discuss the future perspectives of currently available SRLs, focusing on the use of biomarkers of response and precision medicine, new formulations of these SRLs and new drugs, which are under development. Precision medicine, which is based on biomarkers of response to treatment, will help guide the decision-making process by allowing physicians to choose the appropriate drug for each patient and improving response rates. New formulations of available SRLs, such as oral, subcutaneous depot and nasal octreotide, may improve patients’ adherence to treatment and quality of life since there will be more options available that better suit each patient. Finally, new drugs, such as paltusotine, somatropin, ONO-5788 and ONO-ST-468, may improve treatment adherence and present higher efficacy than currently available drugs.

Pharmacotherapy of Bipolar Disorder

2016 ◽  
pp. 384-397
Author(s):  
Jay D. Amsterdam ◽  
Janusz K. Rybakowski
Keyword(s):  
Bipolar Disorder ◽  
First Generation ◽  
Psychiatric Comorbidity ◽  
Antidepressant Drugs ◽  
Term Treatment ◽  
Affective States ◽  
Pharmacological Interventions ◽  
Long Term Treatment ◽  
Depressive Episodes

Bipolar disorder (BD) is a recurrent and often chronic condition that is characterized by episodes of mania, hypomania, depression, and mixed affective states. BD affects up to 5% of the population, ranks sixth as a cause of worldwide disability among persons 15 to 44 years old, and has an estimated lifetime suicide rate of 10–20%. Pharmacotherapy remains one of the most important interventions for initial and long-term treatment of BD. In this chapter, pharmacological interventions for acute manic episodes, for acute depressive episodes, and for the prevention of recurrent affective episodes of either type are systematically presented, with special emphasis on the use of first-generation and second-generation mood-stabilizing drugs and antidepressant drugs. Special issues related to pharmacotherapy of BD are also discussed such as rapid cycling BD, mixed affective states, psychiatric comorbidity, and pregnancy and the postpartum period.

Machine Learning-based Prediction Model for Treatment of Acromegaly With First-generation Somatostatin Receptor Ligands

2021 ◽  
Author(s):  
Luiz Eduardo Wildemberg ◽  
Aline Helen da Silva Camacho ◽  
Renan Lyra Miranda ◽  
Paula C L Elias ◽  
Nina R de Castro Musolino ◽  
...  
Keyword(s):  
Machine Learning ◽  
Support Vector Machine ◽  
Prediction Model ◽  
Predictive Value ◽  
First Generation ◽  
Somatostatin Receptor ◽  
Support Vector ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Igf I

Abstract Context Artificial intelligence (AI), in particular machine learning (ML), may be used to deeply analyze biomarkers of response to first-generation somatostatin receptor ligands (fg-SRLs) in the treatment of acromegaly. Objective To develop a prediction model of therapeutic response of acromegaly to fg-SRL. Methods Patients with acromegaly not cured by primary surgical treatment and who had adjuvant therapy with fg-SRL for at least 6 months after surgery were included. Patients were considered controlled if they presented growth hormone (GH) &lt;1.0 ng/mL and normal age-adjusted insulin-like growth factor (IGF)-I levels. Six AI models were evaluated: logistic regression, k-nearest neighbor classifier, support vector machine, gradient-boosted classifier, random forest, and multilayer perceptron. The features included in the analysis were age at diagnosis, sex, GH, and IGF-I levels at diagnosis and at pretreatment, somatostatin receptor subtype 2 and 5 (SST2 and SST5) protein expression and cytokeratin granulation pattern (GP). Results A total of 153 patients were analyzed. Controlled patients were older (P = .002), had lower GH at diagnosis (P = .01), had lower pretreatment GH and IGF-I (P &lt; .001), and more frequently harbored tumors that were densely granulated (P = .014) or highly expressed SST2 (P &lt; .001). The model that performed best was the support vector machine with the features SST2, SST5, GP, sex, age, and pretreatment GH and IGF-I levels. It had an accuracy of 86.3%, positive predictive value of 83.3% and negative predictive value of 87.5%. Conclusion We developed a ML-based prediction model with high accuracy that has the potential to improve medical management of acromegaly, optimize biochemical control, decrease long-term morbidities and mortality, and reduce health services costs.

scholarly journals Clinical guideline recommendations for antipsychotic long-acting injections

2009 ◽  
Vol 195 (S52) ◽  
pp. s63-s67 ◽  
Author(s):  
John M. Kane ◽  
Carlos Garcia-Ribera
Keyword(s):  
First Generation ◽  
Term Treatment ◽  
First Episode ◽  
Patterns Of Use ◽  
Episode Psychosis ◽  
Long Term Treatment ◽  
Long Acting ◽  
Over 40 Years ◽  
Subsequent Relapse

BackgroundLong-acting injections (LAIs) of antipsychotic drugs were developed over 40 years ago in an attempt to improve the long-term treatment of schizophrenia.AimsTo review existing guidelines concerning antipsychotic use generally, and LAIs in particular, and how patients might be identified as potential candidates for LAI treatment.MethodLiterature review.ResultsCurrently several first-generation and one second-generation antipsychotic LAIs are available, with others under development. Although the use of LAIs is widespread around the world, patterns of use vary widely. Important considerations regarding the use of LAIs include the indications for long-term pharmacotherapy in schizophrenia in general, the indications for LAIs, the risks associated with LAIs, the need to update guidelines and the issue of cost.ConclusionsThe use of these injections in first-episode psychosis and treatment-refractory schizophrenia is not currently a focus of recommendations, but should be considered. Long-acting injections remain an underutilised option in many countries despite frequent non-adherence with oral medication and subsequent relapse.

scholarly journals Pasireotide in the Personalized Treatment of Acromegaly

2021 ◽  
Vol 12 ◽  
Author(s):  
Manel Puig-Domingo ◽  
Ignacio Bernabéu ◽  
Antonio Picó ◽  
Betina Biagetti ◽  
Joan Gil ◽  
...  
Keyword(s):  
First Generation ◽  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
First Line ◽  
First Line Therapy ◽  
Somatostatin Receptor Ligands ◽  
Therapeutic Algorithm ◽  
Surgical Failure ◽  
Positive Effect ◽  
T2 Mri

The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low SST2 and high expression of SST5, low or mutated AIP condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.

Role of somatostatin receptor ligands in the treatment of acromegaly – review of literature

2011 ◽  
Vol 152 (18) ◽  
pp. 715-721 ◽  
Author(s):  
Orsolya Nemes ◽  
Emese Mezősi
Keyword(s):  
Medical Therapy ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Clinical Manifestations ◽  
Oral Glucose ◽  
Receptor Ligands ◽  
Long Term Outcome ◽  
Somatostatin Receptor Ligands

Acromegaly is a rare disease with typical clinical manifestations. Untreated acromegaly carries a 2-4-fold increase in mortality in long-term outcome. The goal of treatment is double, including biochemical control of the disease (normalization of serum IGF1 levels compared to age and gender matched controls, GH levels below 1 ng/ml after oral glucose load, or random GH below 2.5 ng/ml) and control of the tumor mass. The therapeutic modalities currently available for the treatment of acromegaly are: surgery, medical therapy, radiation therapy and their combinations. The cornerstones of medical therapy in acromegaly are the somatostatin receptor ligands due to their effectiveness in controlling GH excess in 60-70 % of patients and their beneficial effects on tumor volume. Somatostatin analogues have an established role as adjuvant therapy after non-curative surgery, and evidence suggests their use as primary treatment for selected patients. The long-term use of somatostatin receptor ligands is safe and they are well tolerated. Future medical therapy consists of pasireotide, a novel, universal somatostatin receptor agonist, and a new class of drugs named dopastatins. The latter so-called chimeric molecules have strong affinity for somatostatin receptors and dopamine-2 receptors, resulting in a more effective blocking of GH secretion, according to preliminary data. The authors of this paper review the current medical therapy of acromegaly, focusing on the role of somatostatin receptor ligands. Orv. Hetil., 2011, 152, 715–721.

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