scholarly journals Phase I study of pasireotide (SOM 230) and everolimus (RAD001) in advanced neuroendocrine tumors

2012 ◽  
Vol 19 (5) ◽  
pp. 615-623 ◽  
Author(s):  
Jennifer A Chan ◽  
David P Ryan ◽  
Andrew X Zhu ◽  
Thomas A Abrams ◽  
Brian M Wolpin ◽  
...  
Keyword(s):  
Phase I ◽  
Neuroendocrine Tumors ◽  
Phase I Study ◽  
Tumor Regression ◽  
Somatostatin Receptor ◽  
Preliminary Evidence ◽  
Response To Therapy ◽  
Receptor Subtypes ◽  
Somatostatin Receptor Subtypes ◽  
Grade 3

Octreotide and everolimus have demonstrated efficacy in neuroendocrine tumors. Pasireotide is a somatostatin analog with binding affinity to a broader range of somatostatin receptor subtypes than octreotide. We performed a phase I study to evaluate the safety and feasibility of combining pasireotide with everolimus in patients with advanced neuroendocrine tumors. Cohorts of patients with advanced neuroendocrine tumors were treated with escalating doses of pasireotide (600–1200 μg s.c. b.i.d., followed by pasireotide LAR 40–60 mg i.m. monthly) and everolimus (5–10 mg daily). Twenty-one patients were treated. Dose-limiting toxicities consisting of grade 3 rash and grade 3 diarrhea were observed. Twelve patients were safely treated at the maximum protocol-defined dose level of pasireotide LAR 60 mg i.m. monthly and everolimus 10 mg daily. Hyperglycemia was common; other observed toxicities were consistent with the known toxicities of either agent alone. Partial tumor response was observed in one patient; 17 (81%) patients experienced at least some tumor regression as their best response to therapy. In conclusion, pasireotide LAR 60 mg i.m. monthly in combination with everolimus 10 mg daily is feasible and associated with preliminary evidence of antitumor activity in patients with advanced neuroendocrine tumors. Further studies evaluating this combination are warranted.

Prognostic Value of Somatostatin Receptor Subtypes in Pancreatic Neuroendocrine Tumors

Pancreas ◽  
2016 ◽  
Vol 45 (2) ◽  
pp. 187-192 ◽  
Author(s):  
Ki Byung Song ◽  
Song Cheol Kim ◽  
Ji Hun Kim ◽  
Dong-Wan Seo ◽  
Seung-Mo Hong ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Prognostic Value ◽  
Somatostatin Receptor ◽  
Receptor Subtypes ◽  
Pancreatic Neuroendocrine Tumors ◽  
Somatostatin Receptor Subtypes

Monoclonal Antibodies against the Human Somatostatin Receptor Subtypes 1–5: Development and Immunohistochemical Application in Neuroendocrine Tumors

2011 ◽  
Vol 95 (3) ◽  
pp. 232-247 ◽  
Author(s):  
Herbert A. Schmid ◽  
Chiara Lambertini ◽  
Harmke H. van Vugt ◽  
Patrizia Barzaghi-Rinaudo ◽  
Judith Schäfer ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Neuroendocrine Tumors ◽  
Somatostatin Receptor ◽  
Receptor Subtypes ◽  
Somatostatin Receptor Subtypes

scholarly journals Phase I study of the 177Lu-DOTA0-Tyr3-Octreotate (lutathera) in combination with nivolumab in patients with neuroendocrine tumors of the lung

2020 ◽  
Vol 8 (2) ◽  
pp. e000980
Author(s):  
Chul Kim ◽  
Stephen V Liu ◽  
Deepa S Subramaniam ◽  
Tisdrey Torres ◽  
Massimo Loda ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Neuroendocrine Tumors ◽  
Phase I Study ◽  
Somatostatin Receptors ◽  
Atypical Carcinoid ◽  
Platinum Based Chemotherapy ◽  
Level 1 ◽  
Grade 3 ◽  
Level 2

BackgroundLutathera is a 177Lutetium-labeled somatostatin analog approved for the treatment of gastroenteropancreatic neuroendocrine tumors (NETs). Somatostatin receptors are expressed in small cell lung cancer (SCLC). Nivolumab, an anti-PD-1 antibody, may act synergistically with lutathera to generate antitumor immunity. We conducted a phase I study of lutathera plus nivolumab in patients with advanced NETs of the lung.MethodsPatients with relapsed/refractory extensive-stage SCLC (ES-SCLC), non-progressing ES-SCLC after first-line platinum-based chemotherapy, or advanced grade I-II pulmonary NETs were eligible. The primary objective was to determine the recommended phase 2 dose (RP2D). The phase I portion followed a standard 3+3 design, assessing two dose levels (dose level 1: lutathera 3.7 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks; dose level 2: lutathera 7.4 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks).ResultsNine patients were enrolled (six ES-SCLC, two pulmonary atypical carcinoid, one high-grade pulmonary neuroendocrine carcinoma). No dose-limiting toxicities (DLTs) were observed at dose level 1. At dose level 2, one patient with refractory ES-SCLC developed a DLT (grade 3 rash). The most common treatment-related adverse events (TRAEs) were lymphopenia (n=7), thrombocytopenia (n=4), anemia (n=3), and nausea (n=3). The most common grade 3 TRAE was lymphopenia (n=4). Among the seven patients with measurable disease, one patient with ES-SCLC had a partial response. Two patients with pulmonary atypical carcinoid had stable disease lasting 6 months. The RP2D was dose level 2.ConclusionsLutathera plus nivolumab was well tolerated and showed signs of antitumor activity. This combination warrants further exploration.Trial registration numberNCT03325816

Could somatostatin receptor subtypes (sst) expression be considered as positive prognostic factor in patients with digestive neuroendocrine tumors (dNETs)?

2001 ◽  
Vol 120 (5) ◽  
pp. A762-A763
Author(s):  
Vito D. Corleto ◽  
Sara Ciardi ◽  
Ottavia De Luca ◽  
Alessandra Moretti ◽  
Francesco Panzuto ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Neuroendocrine Tumors ◽  
Somatostatin Receptor ◽  
Receptor Subtypes ◽  
Somatostatin Receptor Subtypes

scholarly journals Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors

2014 ◽  
Vol 22 (1) ◽  
pp. 1-9 ◽  
Author(s):  
M Cives ◽  
P L Kunz ◽  
B Morse ◽  
D Coppola ◽  
M J Schell ◽  
...  
Keyword(s):  
Phase Ii ◽  
Somatostatin Receptor ◽  
Favorable Effect ◽  
Clinical Activity ◽  
Receptor Subtypes ◽  
Open Label ◽  
Radiographic Response ◽  
Somatostatin Receptor Subtypes ◽  
Grade 3 ◽  
Long Acting

Pasireotide long-acting repeatable (LAR) is a novel somatostatin analog (SSA) with avid binding affinity to somatostatin receptor subtypes 1, 2, 3 (SSTR1,2,3) and 5 (SSTR5). Results from preclinical studies indicate that pasireotide can inhibit neuroendocrine tumor (NET) growth more robustly than octreotidein vitro. This open-label, phase II study assessed the clinical activity of pasireotide in treatment-naïve patients with metastatic grade 1 or 2 NETs. Patients with metastatic pancreatic and extra-pancreatic NETs were treated with pasireotide LAR (60 mg every 4 weeks). Previous systemic therapy, including octreotide and lanreotide, was not permitted. Tumor assessments were performed every 3 months using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), overall radiographic response rate (ORR), and safety. Twenty-nine patients were treated with pasireotide LAR (60 mg every 4 weeks) and 28 were evaluable for response. The median PFS was 11 months. The most favorable effect was observed in patients with low hepatic tumor burden, normal baseline chromogranin A, and high tumoral SSTR5expression. Median OS has not been reached; the 30-month OS rate was 70%. The best radiographic response was partial response in one patient (4%), stable disease in 17 patients (60%), and progressive disease in ten patients (36%). Although grade 3/4 toxicities were rare, pasireotide LAR treatment was associated with a 79% rate of hyperglycemia including 14% grade 3 hyperglycemia. Although pasireotide appears to be an effective antiproliferative agent in the treatment of advanced NETs, the high incidence of hyperglycemia raises concerns regarding its suitability as a first-line systemic agent in unselected patients. SSTR5expression is a potentially predictive biomarker for response.

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