Cargando…

A prospective phase II study of pre-operative chemotherapy then short-course radiotherapy for high risk rectal cancer: COPERNICUS

BACKGROUND: Neoadjuvant chemotherapy (NAC) allows earlier treatment of rectal cancer micro-metastases but is not standard of care. There are currently no biomarkers predicting long-term progression-free survival (PFS) benefit from NAC. PATIENTS AND METHODS: In this single arm phase II trial, patient...

Descripción completa

Detalles Bibliográficos
Autores principales: Gollins, Simon, West, Nicholas, Sebag-Montefiore, David, Susnerwala, Shabbir, Falk, Stephen, Brown, Nick, Saunders, Mark, Quirke, Philip, Ray, Ruby, Parsons, Philip, Griffiths, Gareth, Maughan, Tim, Adams, Richard, Hurt, Chris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173784/
https://www.ncbi.nlm.nih.gov/pubmed/30116024
http://dx.doi.org/10.1038/s41416-018-0209-4
_version_ 1783361182541807616
author Gollins, Simon
West, Nicholas
Sebag-Montefiore, David
Susnerwala, Shabbir
Falk, Stephen
Brown, Nick
Saunders, Mark
Quirke, Philip
Ray, Ruby
Parsons, Philip
Griffiths, Gareth
Maughan, Tim
Adams, Richard
Hurt, Chris
author_facet Gollins, Simon
West, Nicholas
Sebag-Montefiore, David
Susnerwala, Shabbir
Falk, Stephen
Brown, Nick
Saunders, Mark
Quirke, Philip
Ray, Ruby
Parsons, Philip
Griffiths, Gareth
Maughan, Tim
Adams, Richard
Hurt, Chris
author_sort Gollins, Simon
collection PubMed
description BACKGROUND: Neoadjuvant chemotherapy (NAC) allows earlier treatment of rectal cancer micro-metastases but is not standard of care. There are currently no biomarkers predicting long-term progression-free survival (PFS) benefit from NAC. PATIENTS AND METHODS: In this single arm phase II trial, patients with non-metastatic magnetic resonance imaging (MRI)-defined operable rectal adenocarcinoma at high risk of post-operative metastatic recurrence, received 8 weeks of oxaliplatin/fluorouracil NAC then short-course preoperative radiotherapy (SCPRT) before immediate surgery. Sixteen weeks of post-operative adjuvant chemotherapy (AC) was planned. A pelvic MRI was performed at week 9 immediately post-NAC, before SCPRT. The primary end point was feasibility assessed by completion of protocol treatment up to and including surgery. Secondary endpoints included compliance, toxicity, downstaging efficacy, and PFS. RESULTS: In total 60 patients were recruited May 2012–June 2014. In total 57 patients completed protocol treatment, meeting the primary endpoint. Compliance with NAC was much better than AC: Comparing NAC vs. AC, the median percentage dose intensity for fluoropyrimidine was 100% vs. 63% and for oxaliplatin 100% vs. 45%. Treatment-related toxicity was acceptable with no treatment-related deaths. Post-NAC MRI showed 44 tumours (73%) were T-downstaged and 22 (37%) had excellent MRI tumour regression grade (mrTRG 1–2). Median follow-up was 27 months with 2-year PFS of 86.2% (10 events). On exploratory analysis, post-NAC mrTRG predicted PFS with no event among those with excellent regression. CONCLUSION: The regimen was well tolerated with effective downstaging and encouraging PFS. mrTRG response to NAC may be a new prognostic factor for long-term PFS, but needs validation in larger studies.
format Online
Article
Text
id pubmed-6173784
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-61737842019-09-04 A prospective phase II study of pre-operative chemotherapy then short-course radiotherapy for high risk rectal cancer: COPERNICUS Gollins, Simon West, Nicholas Sebag-Montefiore, David Susnerwala, Shabbir Falk, Stephen Brown, Nick Saunders, Mark Quirke, Philip Ray, Ruby Parsons, Philip Griffiths, Gareth Maughan, Tim Adams, Richard Hurt, Chris Br J Cancer Article BACKGROUND: Neoadjuvant chemotherapy (NAC) allows earlier treatment of rectal cancer micro-metastases but is not standard of care. There are currently no biomarkers predicting long-term progression-free survival (PFS) benefit from NAC. PATIENTS AND METHODS: In this single arm phase II trial, patients with non-metastatic magnetic resonance imaging (MRI)-defined operable rectal adenocarcinoma at high risk of post-operative metastatic recurrence, received 8 weeks of oxaliplatin/fluorouracil NAC then short-course preoperative radiotherapy (SCPRT) before immediate surgery. Sixteen weeks of post-operative adjuvant chemotherapy (AC) was planned. A pelvic MRI was performed at week 9 immediately post-NAC, before SCPRT. The primary end point was feasibility assessed by completion of protocol treatment up to and including surgery. Secondary endpoints included compliance, toxicity, downstaging efficacy, and PFS. RESULTS: In total 60 patients were recruited May 2012–June 2014. In total 57 patients completed protocol treatment, meeting the primary endpoint. Compliance with NAC was much better than AC: Comparing NAC vs. AC, the median percentage dose intensity for fluoropyrimidine was 100% vs. 63% and for oxaliplatin 100% vs. 45%. Treatment-related toxicity was acceptable with no treatment-related deaths. Post-NAC MRI showed 44 tumours (73%) were T-downstaged and 22 (37%) had excellent MRI tumour regression grade (mrTRG 1–2). Median follow-up was 27 months with 2-year PFS of 86.2% (10 events). On exploratory analysis, post-NAC mrTRG predicted PFS with no event among those with excellent regression. CONCLUSION: The regimen was well tolerated with effective downstaging and encouraging PFS. mrTRG response to NAC may be a new prognostic factor for long-term PFS, but needs validation in larger studies. Nature Publishing Group UK 2018-08-17 2018-09-11 /pmc/articles/PMC6173784/ /pubmed/30116024 http://dx.doi.org/10.1038/s41416-018-0209-4 Text en © The Author(s) 2018 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Gollins, Simon
West, Nicholas
Sebag-Montefiore, David
Susnerwala, Shabbir
Falk, Stephen
Brown, Nick
Saunders, Mark
Quirke, Philip
Ray, Ruby
Parsons, Philip
Griffiths, Gareth
Maughan, Tim
Adams, Richard
Hurt, Chris
A prospective phase II study of pre-operative chemotherapy then short-course radiotherapy for high risk rectal cancer: COPERNICUS
title A prospective phase II study of pre-operative chemotherapy then short-course radiotherapy for high risk rectal cancer: COPERNICUS
title_full A prospective phase II study of pre-operative chemotherapy then short-course radiotherapy for high risk rectal cancer: COPERNICUS
title_fullStr A prospective phase II study of pre-operative chemotherapy then short-course radiotherapy for high risk rectal cancer: COPERNICUS
title_full_unstemmed A prospective phase II study of pre-operative chemotherapy then short-course radiotherapy for high risk rectal cancer: COPERNICUS
title_short A prospective phase II study of pre-operative chemotherapy then short-course radiotherapy for high risk rectal cancer: COPERNICUS
title_sort prospective phase ii study of pre-operative chemotherapy then short-course radiotherapy for high risk rectal cancer: copernicus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173784/
https://www.ncbi.nlm.nih.gov/pubmed/30116024
http://dx.doi.org/10.1038/s41416-018-0209-4
work_keys_str_mv AT gollinssimon aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT westnicholas aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT sebagmontefioredavid aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT susnerwalashabbir aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT falkstephen aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT brownnick aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT saundersmark aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT quirkephilip aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT rayruby aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT parsonsphilip aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT griffithsgareth aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT maughantim aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT adamsrichard aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT hurtchris aprospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT gollinssimon prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT westnicholas prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT sebagmontefioredavid prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT susnerwalashabbir prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT falkstephen prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT brownnick prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT saundersmark prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT quirkephilip prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT rayruby prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT parsonsphilip prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT griffithsgareth prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT maughantim prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT adamsrichard prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus
AT hurtchris prospectivephaseiistudyofpreoperativechemotherapythenshortcourseradiotherapyforhighriskrectalcancercopernicus