Neoadjuvant chemotherapy for resectable oesophageal and junctional adenocarcinoma: Results from the UK Medical Research Council randomised OEO5 trial (ISRCTN 01852072).

Abstract

4002 Background: Neoadjuvant chemotherapy (2 cycles cisplatin/5 fluorouracil) (CF) followed by surgery is a standard of care for locally advanced oesophageal cancer. We investigated whether more chemotherapy (4 cycles epirubicin/cisplatin /capecitabine (ECX)) would improve outcomes. Methods: A multi-centre, randomised, phase III trial comparing 2 cycles of CF with 4 cycles of ECX followed by oesophagectomy with 2-field lymphadenectomy for lower oesophageal and junctional (Types I and II) adenocarcinoma. Primary outcome was overall survival (OS); 842 patients (677 deaths) would detect an increase in 3-year survival from 30% to 38% (or 37%) with 82% (or 70%) power with 2α = 5%. Deaths accrued more slowly than anticipated but the Independent Data Monitoring Committee considered the data sufficiently robust for release. Secondary outcomes include disease-free (DFS) and progression-free survival (PFS), pathological R0 resection rate, Mandard grade and quality of life. Results: From 2005-2011, 897 patients (451 CF, 446 ECX) from 72 UK centres were randomly allocated (1:1). Baseline characteristics were similar between the groups (overall, male 90%, median age 62 (IQR 56-67), staging included PET 60%, T3 N0 22%, T3 N1 65%). 96% CF received 2 cycles, 89% ECX > 3 cycles. Grade 3/4 toxicity was lower with CF (30% v 47% p < 0.001.) Of those patients having a resection R0 rates were CF 60%, ECX 66% with a Mandard grade ≤ 3 achieved in CF 15% v ECX 32% with 3 and 11% achieving complete response. Post-operative complications were similar (CF 57%, ECX 62%) as were deaths at 30 (CF 2%, ECX 2%) and 90 days post-surgery (CF 4%, ECX 5%). PFS and DFS favoured ECX, hazard ratio (HR, 95% CI) PFS 0.86 (0.74-1.01), DFS 0.88 (0.75-1.03). HR for OS was 0.92 (0.79-1.08, p = 0.3017) based on 315 CF and 298 ECX deaths, with similar 3 year survival rates CF 39% (35-44%) vs ECX 42% (37-46%). Conclusions: There is some evidence of a benefit from the prolonged ECX regimen, in terms of PFS, DFS and tumour regression at resection, but this does not translate into a survival benefit. Overall chemotherapy toxicity was higher with 4 cycles of ECX compared to 2 cycles of CF but surgical morbidity was not increased. Clinical trial information: 01852072.