Neoadjuvant capecitabine and oxaliplatin (CAPOX) followed by chemoradiation (CRT) in high-risk rectal cancer: A single-institution experience.

Abstract

e14100 Background: Total Mesorectal Excision (TME) is standard of care in early rectal cancer. Pre-operative CRT facilitates microscopic complete resection (R0), improving outcome in high risk disease. Recent Phase 2 studies investigated the role of neoadjuvant CAPOX chemotherapy pre-CRT with promising results. We have adopted this strategy in high risk cancers with threatened circumferential resection margin (CRM) on MRI, and report our institution’s early outcome data. Methods: Retrospective data was collected on 37 patients with high risk disease treated March 2007 to December 2011. Patients received 12 weeks oxaliplatin (130mg/m2) and capecitabine (1000mg/m2 BD for 14 days) every 3 weeks, followed by CRT (45 Gy/ 25 #) with concurrent capecitabine (800mg/m2 BD). 11/37 patients had a 5.4 Gy/ 3 # boost with CRT. 4 patients were in a clinical trial, 2 of whom had cetuximab in addition to CAPOX. Patients deemed operable on repeat MRI had TME and 4 cycles of adjuvant CAPOX. Results: Median age was 64 (33-78) and male: female ratio 2.1:1. Median follow-up was 22 months (1.9-53.7). 2 patients did not complete 4 cycles neoadjuvant CAPOX due to toxicity. Median time to surgery post CRT was 6.6 weeks (4.7-10 weeks). 1 patient had an embolic event and femoral embolectomy. 7/31 (23%) patients had no post-operative chemotherapy (4 wound; 2 previous toxicity; 1 comorbidity). Radiological response rates post CRT were 26/34 (76%). 2 patients progressed and were unable to have radical surgery. 1 further patient was found to have unsuspected metastatic disease (liver) at time of surgery. 28/35 (80%) patients had R0 resection and pathological complete response (pCR) was 6/37 (16%). 2 year DFS and OS was 89% and 91.3%. Conclusions: Our outcomes, within an unselected cohort, reflect outcomes consistent with published trial data and support routine use of pre-operative CAPOX and CRT in high risk rectal cancers. This strategy is feasible in a non-trial population, and offers the benefit of early sterilisation of micrometastases, better prediction of chemotherapy response and facilitates the incorporation of novel agents within neoadjuvant window studies.