Cargando…

Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT‐ROC feasibility study

BACKGROUND: Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phas...

Descripción completa

Detalles Bibliográficos
Autores principales: Alexandre, L., Clark, A. B., Walton, S., Lewis, M. P., Kumar, B., Cheong, E. C., Warren, H., Kadirkamanathan, S. S., Parsons, S. L., Dresner, S. M., Sims, E., Jones, M., Hammond, M., Flather, M., Loke, Y. K., Swart, A. M., Hart, A. R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996637/
https://www.ncbi.nlm.nih.gov/pubmed/32011825
http://dx.doi.org/10.1002/bjs5.50239
_version_ 1783493544375222272
author Alexandre, L.
Clark, A. B.
Walton, S.
Lewis, M. P.
Kumar, B.
Cheong, E. C.
Warren, H.
Kadirkamanathan, S. S.
Parsons, S. L.
Dresner, S. M.
Sims, E.
Jones, M.
Hammond, M.
Flather, M.
Loke, Y. K.
Swart, A. M.
Hart, A. R.
author_facet Alexandre, L.
Clark, A. B.
Walton, S.
Lewis, M. P.
Kumar, B.
Cheong, E. C.
Warren, H.
Kadirkamanathan, S. S.
Parsons, S. L.
Dresner, S. M.
Sims, E.
Jones, M.
Hammond, M.
Flather, M.
Loke, Y. K.
Swart, A. M.
Hart, A. R.
author_sort Alexandre, L.
collection PubMed
description BACKGROUND: Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT. METHODS: For this multicentre, double‐blind, parallel‐group, randomized, placebo‐controlled feasibility trial, adults with OAC (including Siewert I–II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival. RESULTS: A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26·7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low‐density lipoprotein cholesterol levels by 3 months (adjusted mean difference −0·83 (95 per cent c.i. −1·4 to −0·22) mmol/l; P = 0·009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow‐up. Adverse events were similar between the groups. Quality‐of‐life data were complete for 98·3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non‐randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise. CONCLUSION: This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (http://www.isrctn/com).
format Online
Article
Text
id pubmed-6996637
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley & Sons, Ltd
record_format MEDLINE/PubMed
spelling pubmed-69966372020-02-05 Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT‐ROC feasibility study Alexandre, L. Clark, A. B. Walton, S. Lewis, M. P. Kumar, B. Cheong, E. C. Warren, H. Kadirkamanathan, S. S. Parsons, S. L. Dresner, S. M. Sims, E. Jones, M. Hammond, M. Flather, M. Loke, Y. K. Swart, A. M. Hart, A. R. BJS Open Randomized Clinical Trials BACKGROUND: Statins inhibit proliferative signalling in oesophageal adenocarcinoma (OAC) and their use is associated with better survival in observational studies. The present study was undertaken to examine the feasibility of assessing adjuvant statin therapy in patients with operable OAC in a phase III RCT. METHODS: For this multicentre, double‐blind, parallel‐group, randomized, placebo‐controlled feasibility trial, adults with OAC (including Siewert I–II lesions) who had undergone oesophagectomy were centrally allocated (1 : 1) to simvastatin 40 mg or matching placebo by block randomization, stratified by centre. Participants, clinicians and investigators were blinded to treatment allocation. Patients received treatment for up to 1 year. Feasibility outcomes were recruitment, retention, drug absorption, adherence, safety, quality of life, generalizability and survival. RESULTS: A total of 120 patients were assessed for eligibility at four centres, of whom 32 (26·7 per cent) were randomized, 16 in each group. Seven patients withdrew. Participants allocated to simvastatin had lower low‐density lipoprotein cholesterol levels by 3 months (adjusted mean difference −0·83 (95 per cent c.i. −1·4 to −0·22) mmol/l; P = 0·009). Median adherence to medication was greater than 90 per cent between 3 and 12 months' follow‐up. Adverse events were similar between the groups. Quality‐of‐life data were complete for 98·3 per cent of questionnaire items. Cardiovascular disease, diabetes and aspirin use were more prevalent in the non‐randomized group, whereas tumour site, stage and grade were similar between groups. Survival estimates were imprecise. CONCLUSION: This RCT supports the conduct and informs the design considerations for a future phase III trial of adjuvant statin therapy in patients with OAC. Registration number: ISRCTN98060456 (http://www.isrctn/com). John Wiley & Sons, Ltd 2019-12-14 /pmc/articles/PMC6996637/ /pubmed/32011825 http://dx.doi.org/10.1002/bjs5.50239 Text en © 2019 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of BJS Society Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Randomized Clinical Trials
Alexandre, L.
Clark, A. B.
Walton, S.
Lewis, M. P.
Kumar, B.
Cheong, E. C.
Warren, H.
Kadirkamanathan, S. S.
Parsons, S. L.
Dresner, S. M.
Sims, E.
Jones, M.
Hammond, M.
Flather, M.
Loke, Y. K.
Swart, A. M.
Hart, A. R.
Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT‐ROC feasibility study
title Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT‐ROC feasibility study
title_full Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT‐ROC feasibility study
title_fullStr Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT‐ROC feasibility study
title_full_unstemmed Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT‐ROC feasibility study
title_short Adjuvant statin therapy for oesophageal adenocarcinoma: the STAT‐ROC feasibility study
title_sort adjuvant statin therapy for oesophageal adenocarcinoma: the stat‐roc feasibility study
topic Randomized Clinical Trials
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996637/
https://www.ncbi.nlm.nih.gov/pubmed/32011825
http://dx.doi.org/10.1002/bjs5.50239
work_keys_str_mv AT alexandrel adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT clarkab adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT waltons adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT lewismp adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT kumarb adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT cheongec adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT warrenh adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT kadirkamanathanss adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT parsonssl adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT dresnersm adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT simse adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT jonesm adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT hammondm adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT flatherm adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT lokeyk adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT swartam adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy
AT hartar adjuvantstatintherapyforoesophagealadenocarcinomathestatrocfeasibilitystudy