Document Detail


Indium-111-pentetreotide prolongs survival in gastroenteropancreatic malignancies.
MedLine Citation:
PMID:  11965607     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Somatostatin and its analogues bind to somatostatin receptors (sst) 1 through 5 that are overexpressed in neuroendocrine neoplasms such as gastroenteropancreatic (GEP) malignancies. After ligand-receptor binding, a fraction of the ligand-receptor complexes internalize. This internalization process is an effective means of delivering cytotoxic radiolabeled somatostatin analogues, especially those emitting short-range decay particles such as Auger electrons, to the neoplastic cell nucleus. Indium-111-pentetreotide, an sst 2 preferring somatostatin analogue with gamma and Auger electron decay characteristics, is commonly used for the scintigraphic evaluation and management of neuroendocrine cancer patients. This clinical trial was performed to determine the effectiveness and tolerability of therapeutic doses of (111)In-pentetreotide in patients with GEP tumors. GEP tumor patients who had failed all forms of conventional therapy, with worsening of tumor-related signs and symptoms and/or radiographically documented progressive disease, an expected survival less than 6 months, and sst positivity as determined by the uptake on a 6.0 mCi (111)In-pentetreotide scan (OctreoScan; Mallinckrodt Medical, Inc, St. Louis, MO), were treated with at least 2 monthly 180-mCi intravenous injections of (111)In-pentetreotide. Baseline clinical assessments, serum chemistries, and plasma pancreastatin levels were measured and repeated before each (111)In-pentetreotide treatment. From February 1997 to February 1998, 27 GEP (24 carcinoid neoplasms with carcinoid syndrome and 3 pancreatic islet cells) patients were accrued, with 26 patients evaluable for clinical and radiographic responses, 21 patients evaluable for biochemical assessments, and 27 patients evaluable for survival analysis and safety. Toxicity was evaluated by using standard National Cancer Institute (NCI) Common Toxicity Criteria guidelines. Clinical benefit occurred in 16 (62%) patients. Pancreastatin levels decreased by 50% or more in 81% of the patients. Objective partial radiographic responses occurred in 2 (8%) patients, and significant tumor necrosis (defined by 20 Hounsfield units or greater decrease from baseline) developed in 7 (27%) patients. The following transient Grades 3/4 NCI Common Toxicity Criteria side effects were observed, respectively: leukocyte: 1/1; platelets: 0/2; hemoglobin: 3/0; bilirubin: 1/3; creatinine: 1/0; neurologic: 1/0. Myeloproliferative disease and/or myelodysplastic syndrome have not been observed in the 6 patients followed-up for 48+ months. The median survival was 18 months (range, 3-54+ mo). Two doses (180 mCi) of (111)In-pentetreotide are safe, well-tolerated, and improve symptoms in 62% of patients, decrease hormonal markers in 81% of patients, decrease Hounsfield units on computed tomography (CT) scans in 27% of patients, with 8% partial radiographic responses and increased expected survival in GEP cancer patients with somatostatin receptor-expressing tumors. The maximal tolerated dose of (111)In-pentetreotide and the optimal dosing schedules remain under investigation.
Authors:
Lowell B Anthony; Eugene A Woltering; Gregory D Espenan; Michele D Cronin; Tom J Maloney; Kevin E McCarthy
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Publication Detail:
Type:  Clinical Trial; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Seminars in nuclear medicine     Volume:  32     ISSN:  0001-2998     ISO Abbreviation:  Semin Nucl Med     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-04-19     Completed Date:  2002-05-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1264464     Medline TA:  Semin Nucl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  123-32     Citation Subset:  IM    
Copyright Information:
Copyright 2002, Elsevier Science.
Affiliation:
Louisiana State University Medical Center, Department of Medicine, the Louisiana State University Health Sciences Center (LSUHSC), Stanley S. Scott Cancer Center, New Orleans, LA 70112, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Carcinoid Tumor / mortality,  radiotherapy*
Carcinoma, Islet Cell / mortality,  radiotherapy*
Female
Gastrointestinal Neoplasms / mortality,  radiotherapy*
Humans
Indium Radioisotopes / adverse effects,  therapeutic use*
Male
Middle Aged
Pancreatic Neoplasms / mortality,  radiotherapy*
Radiopharmaceuticals / adverse effects,  therapeutic use*
Somatostatin / adverse effects,  analogs & derivatives,  therapeutic use*
Survival Rate
Grant Support
ID/Acronym/Agency:
RR05096-07/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Indium Radioisotopes; 0/Radiopharmaceuticals; 138661-02-6/pentetreotide; 51110-01-1/Somatostatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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