TY - JOUR
T1 - Safety, tolerability, pharmacokinetics, and pharmacodynamics of a long-acting release (LAR) formulation of pasireotide (SOM230) in patients with gastroenteropancreatic neuroendocrine tumors
T2 - Results from a randomized, multicenter, open-label, phase i study
AU - Wolin, Edward M.
AU - Hu, Ke
AU - Hughes, Gareth
AU - Bouillaud, Emmanuel
AU - Giannone, Vanessa
AU - Resendiz, Karina Hermosillo
N1 - Funding Information:
Acknowledgments We thank Guoxiang Shen, PhD, of Novartis Oncology (East Hanover, New Jersey), for his contributions to this study and David Gibson, PhD, CMPP, of ApotheCom, for assistance with the preparation of this manuscript. This assistance was funded by Novartis Oncology.
PY - 2013/8
Y1 - 2013/8
N2 - Purpose: Pasireotide (SOM230), a novel multireceptor ligand somatostatin analog (SSA), binds with high affinity to four of the five somatostatin receptor subtypes (sst1-3, 5). This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics profiles of pasireotide long-acting release (LAR) formulation in patients with advanced gastroenteropancreatic neuroendocrine tumor (GEP NET) refractory to other SSAs. Methods: In this randomized, multicenter, open-label, phase II study, patients with biopsy-proven primary or metastatic GEP NET refractory to available SSAs were randomly assigned 1:1:1 to receive pasireotide LAR by deep intragluteal injection at a dose of 20, 40, or 60 mg once every 28 days for 3 months. Results: Forty-two patients received pasireotide LAR. Adverse events were reported by 34 (81 %) patients, with the most frequently reported including diarrhea, fatigue, abdominal pain, and nausea. Mean fasting glucose levels were increased compared with baseline at all points throughout the study. After the third injection of pasireotide LAR, the median trough plasma concentrations on day 84 were 4.82, 12.0, and 19.7 ng/mL in the 20-, 40-, and 60-mg treatment groups, respectively. Drug accumulation was limited for each dose based on the increase in trough concentrations after the first to third injections (accumulation ratios were approximately 1 from all dose levels). Conclusions: This study demonstrated that a new, once-monthly, intramuscular LAR formulation of pasireotide was well tolerated in patients with advanced GEP NET. Steady state levels of plasma pasireotide were achieved after three injections.
AB - Purpose: Pasireotide (SOM230), a novel multireceptor ligand somatostatin analog (SSA), binds with high affinity to four of the five somatostatin receptor subtypes (sst1-3, 5). This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics profiles of pasireotide long-acting release (LAR) formulation in patients with advanced gastroenteropancreatic neuroendocrine tumor (GEP NET) refractory to other SSAs. Methods: In this randomized, multicenter, open-label, phase II study, patients with biopsy-proven primary or metastatic GEP NET refractory to available SSAs were randomly assigned 1:1:1 to receive pasireotide LAR by deep intragluteal injection at a dose of 20, 40, or 60 mg once every 28 days for 3 months. Results: Forty-two patients received pasireotide LAR. Adverse events were reported by 34 (81 %) patients, with the most frequently reported including diarrhea, fatigue, abdominal pain, and nausea. Mean fasting glucose levels were increased compared with baseline at all points throughout the study. After the third injection of pasireotide LAR, the median trough plasma concentrations on day 84 were 4.82, 12.0, and 19.7 ng/mL in the 20-, 40-, and 60-mg treatment groups, respectively. Drug accumulation was limited for each dose based on the increase in trough concentrations after the first to third injections (accumulation ratios were approximately 1 from all dose levels). Conclusions: This study demonstrated that a new, once-monthly, intramuscular LAR formulation of pasireotide was well tolerated in patients with advanced GEP NET. Steady state levels of plasma pasireotide were achieved after three injections.
KW - Gastroenteropancreatic neuroendocrine tumor (GEP NET)
KW - Pasireotide (SOM230)
KW - Pharmacodynamics
KW - Pharmacokinetics
KW - Safety
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U2 - 10.1007/s00280-013-2202-1
DO - 10.1007/s00280-013-2202-1
M3 - Article
C2 - 23765178
AN - SCOPUS:84880918004
SN - 0344-5704
VL - 72
SP - 387
EP - 395
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 2
ER -