TY - JOUR
T1 - NEOSCOPE
T2 - A randomised phase II study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma
AU - Mukherjee, Somnath
AU - Hurt, Christopher Nicholas
AU - Gwynne, Sarah
AU - Sebag-Montefiore, David
AU - Radhakrishna, Ganesh
AU - Gollins, Simon
AU - Hawkins, Maria
AU - Grabsch, Heike I.
AU - Jones, Gareth
AU - Falk, Stephen
AU - Sharma, Ricky
AU - Bateman, Andrew
AU - Roy, Rajarshi
AU - Ray, Ruby
AU - Canham, Jo
AU - Griffiths, Gareth
AU - Maughan, Tim
AU - Crosby, Tom
PY - 2017/3
Y1 - 2017/3
N2 - Background: Oxaliplatin-capecitabine (OxCap) and carboplatin-paclitaxel (CarPac) based neo-adjuvant chemoradiotherapy (nCRT) have shown promising activity in localised, resectable oesophageal cancer.Patients and methods: A non-blinded, randomised (1:1 via a centralised computer system), 'pick a winner' phase II trial. Patients with resectable oesophageal adenocarcinoma >= cT3 and/or >= cN1 were randomised to OxCapRT (oxaliplatin 85 mg/m(2) day 1, 15, 29; capecitabine 625 mg/m(2) bd on days of radiotherapy) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m(2) day 1, 8, 15, 22, 29). Radiotherapy dose was 45 Gy/25 fractions/5 weeks. Both arms received induction OxCap chemotherapy (2 x 3 week cycles of oxaliplatin 130 mg/m(2) day 1, capecitabine 625 mg/m(2) bd days 1-21). Surgery was performed 6-8 weeks after nCRT. Primary end-point was pathological complete response (pCR). Secondary end-points included toxicity, surgical morbidity/mortality, resection rate and overall survival. Statistics: Based on pCR = 35% would, 76 patients (38/arm) gave 90% power (one-sided alpha 10%), implying that arm(s) having >= 10 pCR out of first 38 patients could be considered for phase III trials. ClinicalTrials.gov: NCT01843829. Funder: Cancer Research UK (C44694/A14614).Results: Eighty five patients were randomised between October 2013 and February 2015 from 17 UK centres. Three of 85 (3.5%) died during induction chemotherapy. Seventy-seven patients (OxCapRT = 36; CarPacRT = 41) underwent surgery. The 30-d post-operative mortality was 2/77 (2.6%). Grade III/IV toxicity was comparable between arms, although neutropenia was higher in the CarPacRT arm (21.4% versus 2.6%, p = 0.01). Twelve of 41 (29.3%) (10 of first 38 patients) and 4/36 (11.1%) achieved pCR in the CarPacRT and OxcapRT arms, respectively. Corresponding RO resection rates were 33/41 (80.5%) and 26/36 (72.2%), respectively.Conclusion: Both regimens were well tolerated. Only CarPacRT passed the predefined pCR criteria for further investigation. (C) 2017 The Author(s). Published by Elsevier Ltd.
AB - Background: Oxaliplatin-capecitabine (OxCap) and carboplatin-paclitaxel (CarPac) based neo-adjuvant chemoradiotherapy (nCRT) have shown promising activity in localised, resectable oesophageal cancer.Patients and methods: A non-blinded, randomised (1:1 via a centralised computer system), 'pick a winner' phase II trial. Patients with resectable oesophageal adenocarcinoma >= cT3 and/or >= cN1 were randomised to OxCapRT (oxaliplatin 85 mg/m(2) day 1, 15, 29; capecitabine 625 mg/m(2) bd on days of radiotherapy) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m(2) day 1, 8, 15, 22, 29). Radiotherapy dose was 45 Gy/25 fractions/5 weeks. Both arms received induction OxCap chemotherapy (2 x 3 week cycles of oxaliplatin 130 mg/m(2) day 1, capecitabine 625 mg/m(2) bd days 1-21). Surgery was performed 6-8 weeks after nCRT. Primary end-point was pathological complete response (pCR). Secondary end-points included toxicity, surgical morbidity/mortality, resection rate and overall survival. Statistics: Based on pCR = 35% would, 76 patients (38/arm) gave 90% power (one-sided alpha 10%), implying that arm(s) having >= 10 pCR out of first 38 patients could be considered for phase III trials. ClinicalTrials.gov: NCT01843829. Funder: Cancer Research UK (C44694/A14614).Results: Eighty five patients were randomised between October 2013 and February 2015 from 17 UK centres. Three of 85 (3.5%) died during induction chemotherapy. Seventy-seven patients (OxCapRT = 36; CarPacRT = 41) underwent surgery. The 30-d post-operative mortality was 2/77 (2.6%). Grade III/IV toxicity was comparable between arms, although neutropenia was higher in the CarPacRT arm (21.4% versus 2.6%, p = 0.01). Twelve of 41 (29.3%) (10 of first 38 patients) and 4/36 (11.1%) achieved pCR in the CarPacRT and OxcapRT arms, respectively. Corresponding RO resection rates were 33/41 (80.5%) and 26/36 (72.2%), respectively.Conclusion: Both regimens were well tolerated. Only CarPacRT passed the predefined pCR criteria for further investigation. (C) 2017 The Author(s). Published by Elsevier Ltd.
KW - Oesophageal
KW - Chemotherapy
KW - Radiotherapy
KW - Surgery
KW - Neo-adjuvant
KW - Randomised phase II
KW - PERIOPERATIVE CHEMOTHERAPY
KW - CANCER
KW - TRIAL
KW - CHEMORADIOTHERAPY
KW - OXALIPLATIN
KW - FLUOROURACIL
KW - CAPECITABINE
KW - NEOADJUVANT
KW - CARCINOMA
KW - 5-FLUOROURACIL
U2 - 10.1016/j.ejca.2016.11.031
DO - 10.1016/j.ejca.2016.11.031
M3 - Article
C2 - 28335886
SN - 0959-8049
VL - 74
SP - 38
EP - 46
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -