NEOSCOPE: A randomised phase II study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma

• Published in: European journal of cancer (1990) 2017-03, Vol.74, p.38-46
• Main Authors: Mukherjee, Somnath, Hurt, Christopher Nicholas, Gwynne, Sarah, Sebag-Montefiore, David, Radhakrishna, Ganesh, Gollins, Simon, Hawkins, Maria, Grabsch, Heike I, Jones, Gareth, Falk, Stephen, Sharma, Ricky, Bateman, Andrew, Roy, Rajarshi, Ray, Ruby, Canham, Jo, Griffiths, Gareth, Maughan, Tim, Crosby, Tom
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - therapy; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer; Capecitabine - administration & dosage; Capecitabine - adverse effects; Carboplatin; Carboplatin - administration & dosage; Carboplatin - adverse effects; Chemoradiotherapy; Chemoradiotherapy, Adjuvant - methods; Chemotherapy; Clinical trials; Esophageal cancer; Esophageal Neoplasms - therapy; Esophagus; Female; Hematology, Oncology and Palliative Medicine; Humans; Infusions, Intravenous; Male; Middle Aged; Morbidity; Mortality; Neo-adjuvant; Neoadjuvant Therapy - methods; Neutropenia; Oesophageal; Organoplatinum Compounds - administration & dosage; Organoplatinum Compounds - adverse effects; Original Research; Oxaliplatin; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Patients; Polymerase chain reaction; Preoperative Care - methods; Radiation therapy; Radiotherapy; Randomised phase II; Randomization; Surgery; Toxicity; Treatment Outcome
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2016.11.031

Abstract 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/m2  day 1, 15, 29; capecitabine 625 mg/m2 bd on days of radiotherapy) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m2  day 1, 8, 15, 22, 29). Radiotherapy dose was 45 Gy/25 fractions/5 weeks. Both arms received induction OxCap chemotherapy (2 × 3 week cycles of oxaliplatin 130 mg/m2  day 1, capecitabine 625 mg/m2 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 ≤ 15% not warranting future investigation, but 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 R0 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.