1. A prospective phase II study of pre-operative chemotherapy then short-course radiotherapy for high risk rectal cancer: COPERNICUS.
- Author
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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, and Hurt C
- Subjects
- Adult, Aged, Chemotherapy, Adjuvant, Combined Modality Therapy, Drug Administration Schedule, Feasibility Studies, Female, Fluorouracil adverse effects, Humans, Male, Middle Aged, Neoplasm Staging, Oxaliplatin adverse effects, Patient Compliance statistics & numerical data, Prospective Studies, Radiotherapy Dosage, Radiotherapy, Adjuvant adverse effects, Rectal Neoplasms pathology, Survival Analysis, Treatment Outcome, Fluorouracil administration & dosage, Neoadjuvant Therapy methods, Oxaliplatin administration & dosage, Rectal Neoplasms therapy
- 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.
- Published
- 2018
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