Preparation of Long-acting Somatostatin and GnRH Analogues and their Applications in Tumor Therapy

2021 ◽  
Vol 19 ◽  
Author(s):  
Fang Yu ◽  
Tingting Zhang ◽  
Fenghua Fu ◽  
Aiping Wang ◽  
Xinyong Liu
Keyword(s):  
Patient Compliance ◽  
Treatment Options ◽  
Tumor Therapy ◽  
Somatostatin Analogues ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Preparation Methods ◽  
Gnrh Analogues ◽  
Long Course ◽  
Long Acting ◽  
New Research

Abstract: Hormonal drugs are essential treatment options for some hormone-dependent or hormone-sensitive tumors. The common dosage forms of hormonal drugs have a short half-life. Hence, frequent administration is needed, which results in poor patient compliance. Nevertheless, using drug delivery technology, somatostatin analogues (SSAs) and gonadotropin-releasing hormone (GnRH) analogues are prepared into long-acting formulations that can significantly prolong the action time of these drugs, reducing medication frequency and increasing patient compliance. Such drugs are advantageous when treating acromegaly, gastroenteropancreatic neuroendocrine tumors (GEP-NETs), breast cancer, prostate cancer, and other diseases having a relatively long course. SSAs and GnRH analogues are two typical hormonal drugs, the long-acting formulations of which are essential in clinical practice. This review summarized the preparation methods and clinical application of long-acting formulations in cancer. Further, the action mechanism and new research of SSAs and GnRH analogues were discussed, and suggestions related to the development of long-acting SSAs and GnRH analogues were provided.

Metastatic gastroenteropancreatic neuroendocrine tumors treated with somatostatin analogues: Ten years experience in a third level hospital in Mexico City.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 514-514
Author(s):  
Alberto Pimentel ◽  
Abdel Karim Dip Borunda ◽  
Luis Jonathan Bueno Rosario ◽  
Gloria Martinez Martinez ◽  
Miguel Angel Pluma ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Symptom Control ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Low Grade ◽  
Common Symptom ◽  
First Line ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Long Acting

514 Background: Gastroenteropancreatic neuroendocrine tumors (GEP NET´s) are infrequent tumors, with a variety of symptoms depending of the kind of peptide they secrete as well as the affected organs. Long acting somatostatin analogues have shown an adequate rate of symptom control in functional tumors, they also have demonstrated antiproliferative effect, which is translated in a significant improvement of progression free and overall survival Methods: In this retrospective analysis of patients with metastatic GEP NET treated with long acting somatostatin analogues as first line, treated between 2005 and 2015, we evaluated clinical and pathological features, symptoms, disease control and survival adjusted with OMS classification Results: Our cohort included 95 patients with a mean age of 53 years. Primary affected sites were midgut (29.4%), followed by pNET (17.%), stomach (14.7%), and primary unknown in 14%. 20% of cases were functional tumors with diarrhea as the most common symptom in 70% and flushing in 50%. Considering the whole cohort the most prevalent symptom was abdominal pain in the 50% of cases. The OMS classification showed low grade tumors in 65% and 35% intermediate grade. Most common metastatic organ sites were; liver only 35%, liver and other 30%, peritoneum 10% and lymph nodes in 6%, non-specified sites in 19%. Somatostatine analogues used in first line were octreotide in 80% and lanreotide in 20%. Survival results demonstrated a progression free survival for the whole cohort of 84months. No differences between lanreotide and octreotide were observed. Conclusions: This study represents the first Mexican cohort of patients with GEP NET’s treated with somatostatin analogues with a long follow up.

scholarly journals Efficасу of long-acting somatostatin analogues (SA) in patients (pts) with highly differentiated gastroenteropancreatic neuroendocrine tumors (GEP NETs)

2017 ◽  
Vol 28 ◽  
pp. iii66
Author(s):  
Markovich Alla ◽  
Nadezhda Orel ◽  
Armen Margaryan ◽  
Alexander Kuzminov ◽  
Galina Emelyanova ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Somatostatin Analogues ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Long Acting

scholarly journals Efficacy of Long-Acting Somatostatin Analogues (SA) in Patients (PTS) with Highly Differentiated Gastroenteropancreatic Neuroendocrine Tumors (GEP NETs)

2014 ◽  
Vol 25 ◽  
pp. ii60
Author(s):  
Alla Markovich ◽  
Emelyanova Galina ◽  
Gorbunova Vera ◽  
Orel Nadezhda ◽  
Kuzminov Alexander ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Somatostatin Analogues ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Long Acting

Pancreatic exocrine insufficiency (PI) secondary to chronic use of long-acting (LA) somatostatin analogues (SA) in patients (pts) with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 454-454 ◽  
Author(s):  
Wasif M. Saif ◽  
Melissa H Smith ◽  
Alicia Romano ◽  
Rachna Patel ◽  
Valerie Relias
Keyword(s):  
Early Recognition ◽  
Pancreatic Enzyme ◽  
Somatostatin Analogues ◽  
Exocrine Insufficiency ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Short Acting ◽  
Enzyme Replacement ◽  
Low Fat Diet ◽  
Long Acting ◽  
Chronic Use

454 Background: SA are used in GEP-NETs and acromegaly. Side effects of SAs include biliary disorders, gastrointestinal disorders, injection-site pain and hyperglycemia. PI is often misdiagnosed as disease progression or failure to SA or diagnosed after a delay in pts receiving SA. We present our experience with PI developing in pts following chronic use of SA. Methods: Retrospective chart and pharmacy review of GEP-NETs pts (6/2009 - 6/2017) was completed. Data including demographics, dose/duration of long and short-acting SA, antidiarrheal, pancreatic enzyme replacement (PER), proton pump inhibitors (PPI), chromogranin A (CgA), urine 5-HIAA and quantitative fecal fat test (QFFT) was collected. Results: 110 GEP-NETs pts (Med. age: 56 yr) were identified. 104 pts received LA Octreotide acetate and 6 Somatuline Depot Injection. Of these, 23 received SA octreotide for worsening diarrhea, 96 had intensification of antidiarrheal and 1 got telotristat ethyl. 79 pts were evaluated by nutritionist and/or gastroenterology. QFFT was performed in 47 pts with worsening diarrhea despite stable or improved CgA/urine 5-HIAA. 19 had evidence of steattorrhea and received PER at a dose of 72,000 lipase units per meal. 13 received PPI concomitantly while 6 started when symptoms did not improve with PER. In addition, low fat diet was recommended. 14 of 19 had improvement in diarrhea within 4-8 weeks. 2 pts were non-compliant and 3 were found to have motility disorders. Deficiency of vitamins and trace elements was found in 11 of 19 pts, who received supplementation. Conclusions: Our experience constitutes first study addressing PI as a rare but serious complication of chronic use of SA. Although SA are used to treat diarrhea, paradoxically they can worsen diarrhea secondary to PI. It is believed that SA may inhibit secretion and release of hormones (amylase, trypsin, lipase, secretin, CCK, motilin, bile acid) leading to PI. Early recognition and diagnosis of this under-diagnosed and under-reported side effect of SA can improve not only diarrhea and weight in these pts but also can reduce cost of using short-acting SA and antidiarrheal.

scholarly journals The Dose of Somatostatin Analogues during Pre-Surgical Treatment Is a Key Factor to Achieve Surgical Remission in Acromegaly

Endocrines ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 241-250
Author(s):  
Marta Araujo-Castro ◽  
Eider Pascual-Corrales ◽  
Héctor Pian ◽  
Ignacio Ruz-Caracuel ◽  
Alberto Acitores Cancela ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Surgical Treatment ◽  
Surgical Outcomes ◽  
Pituitary Adenomas ◽  
Somatostatin Analogues ◽  
Beneficial Effects ◽  
Key Factor ◽  
Long Acting ◽  
First Time ◽  
Endocrine Complications

Purpose: to determine whether pre-surgical treatment using long-acting somatostatin analogues (SSAs) may improve surgical outcomes in acromegaly. Methods: retrospective study of 48 patients with acromegaly operated by endoscopic transsphenoidal approach and for first time. Surgical remission was evaluated based on the 2010 criteria. Results: most patients, 83.3% (n = 40), harbored macroadenomas and 31.3% (n = 15) invasive pituitary adenomas. In this case, 14 patients were treated with lanreotide LAR and 6 with octreotide LAR, median monthly doses of 97.5 [range 60–120] and 20 [range 20–30] mg, respectively, for at least 3 months preoperatively. Presurgical variables were comparable between pre-treated and untreated patients (p > 0.05). Surgical remission was more frequent in those pre-treated with monthly doses ≥90 mg of lanreotide or ≥30 mg of octreotide than in untreated or pre-treated with lower doses (OR = 4.64, p = 0.025). However, no differences were found between pre-treated and untreated patients when lower doses were included or between those treated for longer than 6 months compared to those untreated or pre-treated for shorter than 6 months. Similarly, no differences were found either in terms of surgical or endocrine complications (OR = 0.65, p = 0.570), independently of the doses and the duration of SSA treatment (p > 0.05). Conclusions: the dose of SSAs is a key factor during pre-surgical treatment, since the beneficial effects in surgical remission were observed with monthly doses equal or higher than 90 mg of lanreotide and 30 mg of octreotide, but not with lower doses.

scholarly journals The state of PRRT and its sequencing amongst current therapeutic options for gastroenteropancreatic neuroendocrine tumors

2021 ◽  
Author(s):  
Lauren M Raymond ◽  
Tetiana Korzun ◽  
Adel Kardosh ◽  
Kenneth J. Kolbeck ◽  
Rodney Pommier ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Standard Dose ◽  
Peptide Receptor Radionuclide Therapy ◽  
Somatostatin Analogues ◽  
Tumor Burden ◽  
Treatment Modalities ◽  
Its Sequencing ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Reduce Tumor Burden ◽  
Spectrum Of Patients

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common form of neuroendocrine neoplasia, but there is no current consensus for the sequencing of approved therapies, particularly with respect to peptide receptor radionuclide therapy (PRRT). This comprehensive review evaluates the data supporting approved therapies for GEP-NETs and recommendations for therapeutic sequencing with a focus on how PRRT currently fits within sequencing algorithms. The current recommendations for PRRT sequencing restrict its use to metastatic, inoperable, progressive midgut NETs, however, this may change with emerging data to suggest PRRT might be beneficial as neoadjuvant therapy for inoperable tumors, is more tolerable than other treatment modalities following first-line standard dose somatostatin analogues, and can be used as salvage therapy after disease relapse following prior successful cycles of PRRT. PRRT has also been shown to reduce tumor burden, improve quality of life, and prolong the time to disease progression in a broad spectrum of patients with GEP-NETs. As the various potential benefits of PRRT in GEP-NET therapy continues to expand, it is necessary to review and critically evaluate our treatment algorithms for GEP-NETs.

scholarly journals Efficiency of Conditionally Attenuated Salmonella enterica Serovar Typhimurium in Bacterium-Mediated Tumor Therapy

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Michael Frahm ◽  
Sebastian Felgner ◽  
Dino Kocijancic ◽  
Manfred Rohde ◽  
Michael Hensel ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Tumor Targeting ◽  
Antitumor Effect ◽  
Treatment Options ◽  
Tumor Therapy ◽  
Therapeutic Benefit ◽  
Industrialized Countries ◽  
Content Type ◽  
Serovar Typhimurium ◽  
Therapeutic Molecules

ABSTRACTIncreasing numbers of cancer cases generate a great urge for new treatment options. Applying bacteria likeSalmonella entericaserovar Typhimurium for cancer therapy represents an intensively explored option. These bacteria have been shown not only to colonize solid tumors but also to exhibit an intrinsic antitumor effect. In addition, they could serve as tumor-targeting vectors for therapeutic molecules. However, the pathogenicS. Typhimurium strains used for tumor therapy need to be attenuated for safe application. Here, lipopolysaccharide (LPS) deletion mutants (ΔrfaL, ΔrfaG, ΔrfaH, ΔrfaD, ΔrfaP, and ΔmsbBmutants) ofSalmonellawere investigated for efficiency in tumor therapy. Of such variants, the ΔrfaDand ΔrfaGdeep rough mutants exhibited the best tumor specificity and lowest pathogenicity. However, the intrinsic antitumor effect was found to be weak. To overcome this limitation, conditional attenuation was tested by complementing the mutants with an inducible arabinose promoter. The chromosomal integration of the respective LPS biosynthesis genes into thearaBADlocus exhibited the best balance of attenuation and therapeutic benefit. Thus, the present study establishes a basis for the development of an applicably cancer therapeutic bacterium.IMPORTANCECancer has become the second most frequent cause of death in industrialized countries. This and the drawbacks of routine therapies generate an urgent need for novel treatment options. Applying appropriately modifiedS. Typhimurium for therapy represents the major challenge of bacterium-mediated tumor therapy. In the present study, we demonstrated thatSalmonellabacteria conditionally modified in their LPS phenotype exhibit a safe tumor-targeting phenotype. Moreover, they could represent a suitable vehicle to shuttle therapeutic compounds directly into cancerous tissue without harming the host.

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