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Br J Cancer. 2018 Sep;119(6):697-706. doi: 10.1038/s41416-018-0209-4. Epub 2018 Aug 17.

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

Author information

1
North Wales Cancer Treatment Centre, Bodelwyddan, Denbighshire, LL18 5UJ, UK. simon.gollins@wales.nhs.uk.
2
Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, LS9 7TF, UK.
3
Leeds Institute of Cancer and Pathology, University of Leeds and Leeds Cancer Centre, Leeds, LS9 7TF, UK.
4
Royal Preston Hospital, Fulwood, Preston, PR2 9HT, UK.
5
Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, BS2 8ED, UK.
6
Calderdale Royal Hospital, Salterhebble, Halifax, HX3 0PW, UK.
7
The Christie NHS Foundation Trust, Withington, Manchester, M20 4BX, UK.
8
Centre for Trials Research, Cardiff University, Room 409, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK.
9
NCRI RTTQA, Velindre Cancer Centre, Velindre NHS Trust, Velindre Road, Cardiff, CF14 2TL, UK.
10
Southampton Clinical Trials Unit, Faculty of Medicine, Univeristy of Southampton, Tremona Road, Southampton, SO16 6YD, UK.
11
CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.

Abstract

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.

PMID:
30116024
DOI:
10.1038/s41416-018-0209-4
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