A. De Rosa2, W. Al-Khyatt1, C. Tufarelli3, R. Khan2, S. Iftikhar1 1Derby Hospitals NHS Foundation Trust,Derby, United Kingdom 2University of Nottingham,Faculty Of Medicine & Health Sciences,Nottingham, United Kingdom 3Leicester Cancer Research Centre, University of Leicester,Leicester Department Of Genetics And Genome Biology,Leicester, United Kingdom
Introduction:
Oesophageal cancer (OC) is a male dominant disease with a male: female ratio of 5:1 to 10:1. The gender bias is not attributable to differences in exposure to known risk factors alone. Recent in-vitro studies demonstrate oestrogen receptor expression, and the inhibitory effect of tamoxifen (a selective oestrogen receptor modulator) on OC cell growth. The aim of this pilot study is to determine the feasibility of a future randomised clinical trial by measuring the biological effect of short-term tamoxifen on OC growth in-vivo.
Methods:
In this single-arm, single-centre open study, patients with OC who were not candidates for surgical resection or further chemotherapy were included. Each patient received 80mg of tamoxifen for 4 days followed by 20mg thereafter until gastroscopy and biopsy of the tumour 4 weeks later. The biological response to treatment was assessed by immunohistochemistry using a monoclonal antibody to Ki67. The percentage change of Ki67 expression in pre-tamoxifen and paired post-tamoxifen biopsies was measured. The difference in percentage expression was analysed using the Student’s paired t-test.
Results:
Over a 6-month period, 13 patients consented to the study; median (range) age = 79 (60 – 94). Five patients failed to complete the study and were excluded. Eight patients (6 male with adenocarcinoma and 2 female with squamous cell carcinoma) were included in the final analysis. No adverse events were recorded. After a median (range) duration of 30 (28 – 45) days of tamoxifen treatment, there was no change in the mean±SDKi67 expression between paired pre-tamoxifen (65±29.2%) and post-tamoxifen biopsies (65.6±31.9%, P > 0.05). Of the two women included, there was a decrease in the mean±SD Ki67 expression between pre-tamoxifen (51.5±12.0%) and post-tamoxifen biopsies (22.5±3.5%, P > 0.05).
Conclusion:
This pilot study demonstrates the methodology employed is both feasible and safe, and therefore could be used in the design of a randomised, multicentre phase II study to evaluate the clinical outcomes of tamoxifen in OC. Although the study was underpowered and failed to demonstrate a reduction in OC cell growth with tamoxifen treatment, a reduction in Ki67 expression was observed in biopsies of the two women included in the study. Thus any future phase II study design should also incorporate gender-specific subgroup analysis.