Systematic Reviews
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2015; 21(6): 1945-1955
Published online Feb 14, 2015. doi: 10.3748/wjg.v21.i6.1945
Gastrointestinal neuroendocrine tumors treated with high dose octreotide-LAR: A systematic literature review
Michael S Broder, David Beenhouwer, Jonathan R Strosberg, Maureen P Neary, Dasha Cherepanov
Michael S Broder, David Beenhouwer, Dasha Cherepanov, Partnership for Health Analytic Research, LLC, Beverly Hills, CA 90212, United States
Jonathan R Strosberg, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, United States
Maureen P Neary, Novartis Pharmaceuticals Corporation, East Hanover, NJ 07936, United States
Author contributions: Broder MS and Cherepanov D contributed substantially to conception, design, management of the study, interpretation of data, drafting of the manuscript, revising the manuscript critically for significant intellectual content; Beenhouwer D contributed substantially to conception, design, interpretation of data, drafting of the manuscript or revising it critically for significant intellectual content, performed the search and abstraction of studies; Strosberg JR contributed substantially to interpretation of data, revising the manuscript critically for significant intellectual content; Neary MP contributed substantially to conception, interpretation of data, revision of the manuscript; all authors approved the final manuscript.
Supported by Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080, United States.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Michael S Broder, MD, MSHS, Partnership for Health Analytic Research, LLC, 280 South Beverly Drive, Suite 404, Beverly Hills, CA 90212, United States.
Telephone: +1-310-8589555 Fax: +1-310-8589552
Received: March 26, 2014
Peer-review started: March 26, 2014
First decision: April 28, 2014
Revised: July 31, 2014
Accepted: September 18, 2014
Article in press: September 19, 2014
Published online: February 14, 2015

AIM: To review literature on efficacy and safety of octreotide-long-acting repeatable (LAR) used at doses higher than the Food and Drug Administration (FDA)-approved 30 mg/mo for treatment of neuroendocrine tumors (NETs).

METHODS: We searched PubMed and Cochrane Library from 1998-2012, 5 conferences (American Society of Clinical Oncology, Endocrine Society, European Neuroendocrine Tumor Society, European Society for Medical Oncology, North American Neuroendocrine Tumor Society) from 2000-2013 using MeSH and keyterms including neuroendocrine tumors, carcinoid tumor, carcinoma, neuroendocrine, and octreotide. Bibliographies of accepted articles were also searched. Two reviewers reviewed titles, abstracts, and full-length articles. Studies that reported data on efficacy and safety of ≥ 30 mg/mo octreotide-LAR for NETs in human subjects, published in any language were included in the review.

RESULTS: The search identified 1086 publications, of which 238 underwent full-text review (20 were translated into English); 17 were included in the review. Studies varied in designs, subjects, octreotide-LAR regimens, and definition of outcomes. Eleven studies reported use of higher doses to control symptoms and tumor progression, although symptom severity and formal quality-of-life analysis were not quantitatively measured. Ten studies reported efficacy, describing 260 subjects with doses ranging from 40 mg/mo or 30 mg/3 wk up to 120 mg/mo. Eight studies reported expert clinical opinion that supported dose escalation of octreotide-LAR up to 60 mg/mo for symptom control and suggested increased doses may be effective at preventing tumor progression. Eight studies reported safety; there was no evidence of increased toxicity associated with doses of octreotide-LAR > 30 mg/mo.

CONCLUSION: As reported in this review, octreotide-LAR at doses > 30 mg/mo is being prescribed for symptom and tumor control in NET patients. Furthermore, expert clinical opinion provided support for escalation of somatostatin analogs for refractory hormonal symptoms.

Keywords: Carcinoma, Neuroendocrine, Carcinoid syndrome, Carcinoid tumor, Gastrointestinal neoplasms, Neuroendocrine tumor, Antineoplastic agents, Hormonal, Dose-Response relationship, Drug, Octreotide, Literature review, Efficacy, Effectiveness, Symptom control, Tumor progression control, Diarrhea, Abdominal pain, Flushing

Core tip: Although octreotide-long-acting repeatable (LAR) is Food and Drug Administration approved for alleviating severe diarrhea/flushing associated with metastatic carcinoid tumors at doses ≤ 30 mg every 4 wk, our review found that several studies within the published literature described the use of above-label doses of octreotide-LAR for symptom and tumor control of neuroendocrine tumors. Expert clinical opinion, as reported in this review, supports escalation of somatostatin analogs for patients with refractory hormonal symptoms.