Systematic Reviews
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Jun 28, 2018; 6(2): 9-20
Published online Jun 28, 2018. doi: 10.13105/wjma.v6.i2.9
Systematic literature review of the antitumor effect of octreotide in neuroendocrine tumors
Stephanie M Barrows, Beilei Cai, Catherine Copley-Merriman, Kelly R Wright, Colleen V Castro, Raoudha Soufi-Mahjoubi
Stephanie M Barrows, Catherine Copley-Merriman, Kelly R Wright, RTI Health Solutions, Ann Arbor, MI 48108, United States
Beilei Cai, Raoudha Soufi-Mahjoubi, Novartis Pharmaceuticals, East Hanover, NJ 07936, United States
Colleen V Castro, RTI Health Solutions, Research Triangle Park, NC 27709, United States
Author contributions: Barrows SM did the data curation, project administration and writing (original draft, review and editing); Cai B did the conceptualization, funding acquisition and supervision; Copley-Merriman C did the data curation, supervision and writing (review and editing); Wright KR and Castro CV contributed to the data curation and methodology; Soufi-Mahjoubi R did the conceptualization and supervision; all authors provided review and approval of the final version.
Conflict-of-interest statement: Beilei Cai and Raoudha Soufi-Mahjoubi are employees of Novartis Pharmaceuticals. RTI-HS received funding from Novartis Pharmaceuticals to conduct this work.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Stephanie M Barrows, MA, MPH, Research Scientist, Senior Director, RTI Health Solutions, 3005 Boardwalk St., Suite 105, Ann Arbor, MI 48108, United States. sbarrows@rti.org
Telephone: +1-734-2135419 Fax: +1-734-2136169
Received: March 23, 2018
Peer-review started: March 23, 2018
First decision: April 18, 2018
Revised: April 26, 2018
Accepted: May 15, 2018
Article in press: May 15, 2018
Published online: June 28, 2018
Processing time: 97 Days and 14.7 Hours
ARTICLE HIGHLIGHTS
Research background

Neuroendocrine tumors (NETs) are rare, slow-growing neoplasms that most commonly arise in the gastrointestinal tract, lung, and pancreas. Although approved in the United States only for carcinoid symptom (severe diarrhea/flushing episodes) control and not for tumor control, octreotide has been a mainstay of NET therapy for nearly 3 decades.

Research motivation

Previous literature reviews focused on escalated doses of somatostatin analogs (SSAs) and clinical trials of the antitumor effect of SSAs. At the time of the current review, no systematic reviews summarizing both clinical trial and observational data had been published.

Research objective

The objective of this literature review was to provide a systematic and comprehensive examination of the existing evidence of the antitumor effect of long-acting octreotide in NETs regardless of dosing and to broaden the search to include real-world evidence and clinical trials.

Research methods

A systematic literature review of clinical trials and observational studies was conducted in PubMed, EMBASE, and Cochrane through January 18, 2017. Conference abstracts for 2015 and 2016 from 5 scientific meetings were also searched. To supplement the search, the bibliographic reference lists of relevant systematic review articles were also reviewed. Two independent reviewers screened the titles and abstracts according to predefined inclusion and exclusion criteria. Full-text articles of selected records were obtained, and the 2 independent reviewers further screened each article according to the same predefined inclusion and exclusion criteria.

Research results

Of 41 articles/abstracts identified, 13 unique studies compared octreotide with active or no treatment. Two of the 13 studies were clinical trials; the remaining were observational studies. The phase 3 Placebo-Controlled, Double-Blind, Prospective, Randomized Study of the Effect of Octreotide long-acting repeatable (LAR) in the Control of Tumor Growth in Patients with Metastatic Neuroendocrine Midgut Tumors clinical trial showed that long-acting octreotide significantly prolonged time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs; no statistically significant difference in overall survival (OS) was observed, possibly due to the crossover of placebo patients to octreotide. Retrospective observational studies found that long-acting octreotide use was associated with significantly longer OS than no octreotide use for patients with distant metastases although not for those with local/regional disease.

Research conclusion

The clinical trial and observational studies with informative evidence support long-acting octreotide’s antitumor effect on time to tumor progression and OS. This review showed the rarity of existing studies assessing octreotide’s antitumor effect and recommends that future research is warranted.