Editorial
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Apr 10, 2016; 7(2): 149-154
Published online Apr 10, 2016. doi: 10.5306/wjco.v7.i2.149
Sequential treatment in disseminated well- and intermediate-differentiated pancreatic neuroendocrine tumors: Common sense or low rationale?
Enrique Grande
Enrique Grande, Department of Medical Oncology, Ramón y Cajal University Hospital, 28034 Madrid, Spain
Author contributions: Grande E wrote the article and approved the final wording and editing; no medical writer assistance was needed.
Conflict-of-interest statement: Grande E has served as advisor for GSK, Pfizer, and Lexicon and has delivered lectures for Pfizer, Novartis, IPSEN, and Lexicon.
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: Enrique Grande, MD, Department of Medical Oncology, Ramón y Cajal University Hospital, Carretera de Colmenar Km 9, 1, 28034 Madrid, Spain. egrande@oncologiahrc.com
Telephone: +34-91-3368263
Received: June 14, 2015
Peer-review started: June 16, 2015
First decision: September 22, 2015
Revised: September 24, 2015
Accepted: December 17, 2015
Article in press: December 18, 2015
Published online: April 10, 2016
Abstract

Fortunately, the landscape of the systemic treatment for grade 1 and 2 pancreatic neuroendocrine tumors has changed in the last decade with at least four different alternatives approved in the field. Chemotherapy, somatostatin analogues, sunitinib and everolimus remind valid options according to the most referenced international guidelines. However, and although this is something done in the routine practice, there is a lack of evidence for the use of any of these strategies after failure to the others. Moreover, further sequential alternatives in third or fourth line have never been tested prospectively. The need for a better understanding of the rationale to sequence different systemic options is even greater in non-pancreatic neuroendocrine tumors since available therapies are scarce. Sequential strategies in other solid tumors have led to a clear improvement in overall survival. This is also believed to occur in neuroendocrine tumors but no clear data on it has been delivered yet. We postulate that the different mode of action of the systemic options available for the treatment of neuroendocrine tumors may avoid the complete resistance of one option after the other and that sequential use of these agents will be translated into a longer overall survival of patients. Prospective and randomized trials that seek for the activity of drugs after failure to another systemic alternatives are highly needed in this field of neuroendocrine tumors.

Keywords: Carcinoids, Everolimus, Neuroendocrine tumors, Pancreas, Overcoming resistance, Sequential-treatment, Sunitinib

Core tip: There is a need to improve the rationale we use when approaching to a sequential systemic treatment strategy in disseminated neuroendocrine tumors. Up to now, we do not have level 1 evidence to use any systemic alternative after failure to a prior one. Widely heterogeneous populations have been recruited in larger phase III pivotal trials in neuroendocrine tumors. Therefore, it is difficult to find final conclusions from the registration trials. In this article we aim to summarize the available evidence behind the use of different alternatives after failure to standard somatostatin analogs.