Indium-111-pentetreotide prolongs survival in gastroenteropancreatic malignancies

Lowell B. Anthony, Eugene A. Woltering, Gregory D. Espenan, Michele D. Cronin, Tom J. Maloney, Kevin E. McCarthy

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242 Scopus citations

Abstract

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 111In-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 111Inpentetreotide scan (OctreoScan; Mallinckrodt Medical, Inc, St. Louis, MO), were treated with at least 2 monthly 180-mCi intravenous injections of 111In-pentetreotide. Baseline clinical assessments, serum chemistries, and plasma pancreastatin levels were measured and repeated before each 111Inpentetreotide 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 111In-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 111In-pentetreotide and the optimal dosing schedules remain under investigation.

Original languageEnglish
Pages (from-to)123-132
Number of pages10
JournalSeminars in Nuclear Medicine
Volume32
Issue number2
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
From the Louisiana State University Medical Center, Departments of Medicine, Surgery, and Radiology, the Louisiana State University Health Sciences Center (LSUHSC). Stanley S. Scott Cancer Center, New Orleans, LA; and lso-tex Diagnostics, Inc., Friendswood, TX. Supported in part by NIH-GCRC-RR05096-07 and the LSUHSC Foundation. Address reprint requests to Lowell B. Anthony, MD, Department of Medicine, Division of Hematology and Oncology, Louisiana State University Health Sciences Center, 1542 Tulane Ave, New Orleans, LA 70112. Copyright 2002, Elsevier Science (USA). All rights reserved. 0001-2998/02/3202-0006535.00/0 doi :10.105 3/snuc.2002.317 69

Funding Information:
The authors thank Drs. Thomas O'Dorisio for his assistance in measuring pancreastatin levels; Catherine Anthony, Brian Geb-hardt, and Conrad Hornick for their assistance in developing the basic science background for this clinical investigation. The authors also thank, Judy Norton, LPN, Virginia Garrison, RN, and the Tulane/LSUHSC GCRC staff, the Medical Center of Louisiana Nuclear Medicine technical staff. This project was supported in part by NIH-General Clinical Research Center-RR05096-07 and by the LSUHSC New Orleans Foundation.

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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