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, patients...
| প্রধান লেখক: | , , , , , , , , , , , , , |
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| অন্যান্য লেখক: | |
| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
Springer Nature
2019
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| _version_ | 1826291697098686464 |
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| author | Gollins, S West, N Sebag-Montefiore, D Susnerwala, S Falk, S Brown, N Saunders, M Quirke, P Ray, R Parsons, P Griffiths, G Maughan, T Adams, R Hurt, C |
| author2 | McIntyre, A |
| author_facet | McIntyre, A Gollins, S West, N Sebag-Montefiore, D Susnerwala, S Falk, S Brown, N Saunders, M Quirke, P Ray, R Parsons, P Griffiths, G Maughan, T Adams, R Hurt, C |
| author_sort | Gollins, S |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-07T03:03:18Z |
| format | Journal article |
| id | oxford-uuid:b1ac353b-f883-495d-a0ba-5aece3e6a079 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:03:18Z |
| publishDate | 2019 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:b1ac353b-f883-495d-a0ba-5aece3e6a0792022-03-27T04:05:55ZA prospective phase II study of pre-operative chemotherapy then short-course radiotherapy for high risk rectal cancer: COPERNICUSJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b1ac353b-f883-495d-a0ba-5aece3e6a079EnglishSymplectic Elements at OxfordSpringer Nature2019Gollins, SWest, NSebag-Montefiore, DSusnerwala, SFalk, SBrown, NSaunders, MQuirke, PRay, RParsons, PGriffiths, GMaughan, TAdams, RHurt, CMcIntyre, ABACKGROUND: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. |
| spellingShingle | Gollins, S West, N Sebag-Montefiore, D Susnerwala, S Falk, S Brown, N Saunders, M Quirke, P Ray, R Parsons, P Griffiths, G Maughan, T Adams, R Hurt, C 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 |
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