NEOSCOPE: A randomised phase II study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma.
Oxaliplatin-capecitabine (OxCap) and carboplatin-paclitaxel (CarPac) based neo-adjuvant chemoradiotherapy (nCRT) have shown promising activity in localised, resectable oesophageal cancer.



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/m2day 1, 15, 29; capecitabine 625 mg/m2bd on days of radiotherapy) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m2day 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/m2day 1, capecitabine 625 mg/m2bd 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.



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).



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.



Both regimens were well tolerated. Only CarPacRT passed the predefined pCR criteria for further investigation.
CRUK MRC Oxford Institute for Radiation Oncology Gray Laboratories, Oxford University, Oxford, OX3 7DQ, UK. Electronic address: somnath.mukherjee@oncology.ox.ac.uk.
Somnath
S
Mukherjee
Centre for Trials Research, Cardiff University, 6th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK. Electronic address: hurtcn@cardiff.ac.uk.
Christopher Nicholas
CN
Hurt
South West Wales Cancer Centre, Swansea, SA2 8QA, UK. Electronic address: Sarah.Gwynne@wales.nhs.uk.
Sarah
S
Gwynne
St James's Institute of Oncology, University of Leeds, Cancer Research UK Leeds Centre, St James's University Hospital, Leeds, LS9 7TF, UK. Electronic address: D.SebagMontefiore@leeds.ac.uk.
David
D
Sebag-Montefiore
St James's Institute of Oncology, University of Leeds, Cancer Research UK Leeds Centre, St James's University Hospital, Leeds, LS9 7TF, UK. Electronic address: Ganesh.Radhakrishna@leedsth.nhs.uk.
Ganesh
G
Radhakrishna
North Wales Cancer Treatment Centre, Rhyl, LL18 5UJ, UK. Electronic address: Simon.Gollins@wales.nhs.uk.
Simon
S
Gollins
CRUK MRC Oxford Institute for Radiation Oncology Gray Laboratories, Oxford University, Oxford, OX3 7DQ, UK. Electronic address: maria.hawkins@oncology.ox.ac.uk.
Maria
M
Hawkins
GROW School for Oncology and Developmental Biology, Department of Pathology, Maastricht University Medical Centre, Maastricht, Netherlands; Section of Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, University of Leeds, UK. Electronic address: h.grabsch@maastrichtuniversity.nl.
Heike I
HI
Grabsch
Velindre Cancer Centre, Velindre Hospital, Velindre Road, Cardiff, CF14 2TL, UK. Electronic address: Gareth.Jones9@wales.nhs.uk.
Gareth
G
Jones
Bristol Haematology and Oncology Centre, Bristol, BS2 8ED, UK. Electronic address: Stephen.Falk@UHBristol.nhs.uk.
Stephen
S
Falk
CRUK MRC Oxford Institute for Radiation Oncology Gray Laboratories, Oxford University, Oxford, OX3 7DQ, UK. Electronic address: ricky.sharma@oncology.ox.ac.uk.
Ricky
R
Sharma
Faculty of Medicine, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. Electronic address: a.r.bateman@soton.ac.uk.
Andrew
A
Bateman
Diana Princess of Wales Hospital, Scartho Road, Grimsby, South Humberside, DN33 2BA, UK. Electronic address: Rajarshi.Roy@hey.nhs.uk.
Rajarshi
R
Roy
Centre for Trials Research, Cardiff University, 6th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK. Electronic address: Al-MokhtarR@cardiff.ac.uk.
Ruby
R
Ray
Centre for Trials Research, Cardiff University, 6th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK. Electronic address: CanhamJ@cardiff.ac.uk.
Jo
J
Canham
Southampton Clinical Trials Unit, University of Southampton, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK. Electronic address: G.O.Griffiths@soton.ac.uk.
Gareth
G
Griffiths
CRUK MRC Oxford Institute for Radiation Oncology Gray Laboratories, Oxford University, Oxford, OX3 7DQ, UK. Electronic address: tim.maughan@oncology.ox.ac.uk.
Tim
T
Maughan
Velindre Cancer Centre, Velindre Hospital, Velindre Road, Cardiff, CF14 2TL, UK. Electronic address: Tom.Crosby@wales.nhs.uk.
Tom
T
Crosby
D000230:Adenocarcinoma / Q000628:therapy*; D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods; D004938:Esophageal Neoplasms / Q000628:therapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011300:Preoperative Care / Q000379:methods; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine; D016190:Carboplatin; D017239:Paclitaxel
Chemotherapy; Neo-adjuvant; Oesophageal; Radiotherapy; Randomised phase II; Surgery