Randomized Controlled Trial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2017; 9(8): 333-340
Published online Aug 15, 2017. doi: 10.4251/wjgo.v9.i8.333
Impact of tumour histological subtype on chemotherapy outcome in advanced oesophageal cancer
Michael Davidson, Ian Chau, David Cunningham, Komel Khabra, Timothy Iveson, Tamas Hickish, Matthew Seymour, Naureen Starling
Michael Davidson, Ian Chau, David Cunningham, Komel Khabra, Naureen Starling, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, London SM25PT, United Kingdom
Timothy Iveson, Southampton University Hospital NHS Trust and Salisbury Hospital NHS Foundation Trust, Southampton SO16 6YD, United Kingdom
Tamas Hickish, Department of Haematology and Oncology, Bournemouth University and Poole Hospital NHS Trust, Dorset BH15 2JB, United Kingdom
Matthew Seymour, St James’s Institute of Oncology, St James’s Hospital, Leeds LS9 7TF, United Kingdom
Author contributions: Davidson M prepared manuscript; Khabra K performed statistical analysis; Chau I, Cunningham D, Iveson T, Hickish T, Seymour M and Starling N critically reviewed manuscript.
Institutional review board statement: All three studies included in the following analysis were reviewed by approved research and ethics committees in accordance with UK Medical Research Council regulations and results have previously been published in peer-reviewed journals.
Informed consent statement: All study participants in the three studies included in the following analysis provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
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: Dr. Naureen Starling, Royal Marsden Hospital NHS Foundation Trust, London and Surrey, Fulham Road, London SM25PT, United Kingdom. naureen.starling@rmh.nhs.uk
Fax: +44-208-6439414
Received: January 31, 2017
Peer-review started: February 7, 2017
First decision: March 28, 2017
Revised: May 10, 2017
Accepted: May 18, 2017
Article in press: May 19, 2017
Published online: August 15, 2017
Processing time: 191 Days and 1.6 Hours
Abstract
AIM

To investigate the impact of histology on outcome in advanced oesophageal cancer treated with first-line fluoropyrimidine-based chemotherapy.

METHODS

Individual patient data were pooled from three randomised phase III trials of fluoropyrimidine-based chemotherapy ± platinum/anthracycline in patients with advanced, untreated gastroesophageal adenocarcinoma or squamous cell carcinoma (SCC) randomised between 1994 and 2005. The primary endpoint was overall survival of oesophageal cancer patients according to histology. Secondary endpoints were response rates and a toxicity composite endpoint.

RESULTS

Of the total 1836 randomised patients, 973 patients (53%) were eligible (707 patients with gastric cancer were excluded), 841 (86%) had adenocarcinoma and 132 (14%) had SCC. There was no significant difference in survival between patients with adenocarcinoma and SCC, with median overall survivals of 9.5 mo vs 7.6 mo (HR = 0.85, 95%CI: 0.70-1.03, P = 0.09) and one-year survivals of 38.8% vs 28.2% respectively. The overall response rate to chemotherapy was 44% for adenocarcinoma vs 33% for SCC (P = 0.01). There was no difference in the frequency of the toxicity composite endpoint between the two groups.

CONCLUSION

There was no significant difference in survival between adenocarcinoma and SCC in patients with advanced oesophageal cancer treated with fluoropyrimidine-based chemotherapy despite a trend for worse survival and less chemo-sensitivity in SCC. Tolerance to treatment was similar in both groups. This analysis highlights the unmet need for SCC-specific studies in advanced oesophageal cancer and will aid in the design of future trials of targeted agents.

Keywords: Oesophageal cancer; Adenocarcinoma; Chemotherapy; Squamous; Pooled analysis

Core tip: There is a lack of published data on differential treatment response according to histology in oesophageal cancer. This paper shows improved response rates with first-line chemotherapy and a trend towards improved survival in adenocarcinoma compared to squamous cell carcinoma (SCC). It is increasingly recognised that these histological subtypes represent discrete disease entities with divergent treatment pathways in both the early stage and advanced settings. Novel treatments in SCC remain sparse and there are few dedicated trials in this subtype. This data highlights the poor outcomes seen with chemotherapy alone and the need for further research, particularly for SCC.