NEOSCOPE: a randomised phase {II} study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma: 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: 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/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 × 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 ≤ 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.
Journal Article
38-46
Mukherjee, Somnath
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Hurt, Christopher Nicholas
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Gwynne, Sarah
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Sebag-Montefiore, David
7cd6f558-4265-4adb-b8dd-771f47ab8343
Radhakrishna, Ganesh
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Gollins, Simon
ae092a24-b3fb-4d95-b5af-802a14bd79f8
Hawkins, Maria
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Grabsch, Heike I.
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Jones, Gareth
38e9522d-b348-4e06-8bbe-ce11b48defb4
Falk, Stephen
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Sharma, Ricky
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Bateman, Andrew
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Roy, Rajarshi
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Ray, Ruby
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Canham, Jo
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Griffiths, Gareth
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Maughan, Tim
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Crosby, Tom
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8 February 2017
Mukherjee, Somnath
b2ff936d-d068-48d5-9bb5-9f3431013b5b
Hurt, Christopher Nicholas
618ad9ce-f7a6-4ccc-afc5-e54db97a6f7f
Gwynne, Sarah
0cbce6d8-328d-430e-9f5e-a5885deedac8
Sebag-Montefiore, David
7cd6f558-4265-4adb-b8dd-771f47ab8343
Radhakrishna, Ganesh
9f1b2cb2-3fbe-4cb6-ada9-d8a3c120c937
Gollins, Simon
ae092a24-b3fb-4d95-b5af-802a14bd79f8
Hawkins, Maria
41b00d65-3370-4b78-a6a1-c7ad4bf2e379
Grabsch, Heike I.
92b7b7e0-4876-4633-8c88-7f867409cd5c
Jones, Gareth
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Falk, Stephen
6bda4f5d-d5b0-4558-89d3-9e32cacf202a
Sharma, Ricky
4de2e136-5ae8-4349-8465-3148d5dc8cc4
Bateman, Andrew
a851558d-8b9b-4020-b148-a239c2b26815
Roy, Rajarshi
7de1069c-55ef-4dd8-89e3-1ae379e5c6e5
Ray, Ruby
6a82843d-17d5-4cea-95bd-3680df255324
Canham, Jo
6afb6b5c-7c4f-438e-944e-6cf2abf7dd7d
Griffiths, Gareth
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
Maughan, Tim
9f5b1ca4-9ed7-4100-bf04-c4026e4b5395
Crosby, Tom
d641cb6d-efc6-45ae-b083-a21c599a032c
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 and Crosby, Tom
(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: 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/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 × 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 ≤ 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
Keywords:
Journal Article
Organisations:
Cancer Sciences, Clinical Trials Unit
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Local EPrints ID: 410683
URI: http://eprints.soton.ac.uk/id/eprint/410683
ISSN: 0959-8049
PURE UUID: 9cc3680c-fb4c-42e4-a328-4b6eeb6b4788
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Date deposited: 09 Jun 2017 09:21
Last modified: 03 Sep 2024 01:49
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Contributors
Author:
Somnath Mukherjee
Author:
Christopher Nicholas Hurt
Author:
Sarah Gwynne
Author:
David Sebag-Montefiore
Author:
Ganesh Radhakrishna
Author:
Simon Gollins
Author:
Maria Hawkins
Author:
Heike I. Grabsch
Author:
Gareth Jones
Author:
Stephen Falk
Author:
Ricky Sharma
Author:
Andrew Bateman
Author:
Rajarshi Roy
Author:
Ruby Ray
Author:
Jo Canham
Author:
Tim Maughan
Author:
Tom Crosby
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