NEOSCOPE: a randomised phase {II} study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma
NEOSCOPE: a randomised phase {II} study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma
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.
38-46
Mukherjee, Somnath
81b82408-8d54-4983-a412-81969f5edfdd
Hurt, Christopher Nicholas
bf8b37a0-8f08-4b47-b3f3-6fc65f7ab87f
Gwynne, Sarah
0cbce6d8-328d-430e-9f5e-a5885deedac8
8 February 2017
Mukherjee, Somnath
81b82408-8d54-4983-a412-81969f5edfdd
Hurt, Christopher Nicholas
bf8b37a0-8f08-4b47-b3f3-6fc65f7ab87f
Gwynne, Sarah
0cbce6d8-328d-430e-9f5e-a5885deedac8
Mukherjee, Somnath, Hurt, Christopher Nicholas and Gwynne, Sarah
,
et al.
(2017)
NEOSCOPE: a randomised phase {II} study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma.
European Journal of Cancer, 74, .
(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.
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Accepted/In Press date: 27 November 2016
e-pub ahead of print date: 8 February 2017
Published date: 8 February 2017
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Local EPrints ID: 488236
URI: http://eprints.soton.ac.uk/id/eprint/488236
PURE UUID: 112fc892-2f06-4ed3-bbd2-2e94567a0691
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Date deposited: 19 Mar 2024 17:33
Last modified: 23 Mar 2024 03:13
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Author:
Somnath Mukherjee
Author:
Christopher Nicholas Hurt
Author:
Sarah Gwynne
Corporate Author: et al.
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