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Clinical Trial
. 2017 Mar:74:38-46.
doi: 10.1016/j.ejca.2016.11.031. Epub 2017 Feb 8.

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

Somnath Mukherjee  1 , Christopher Nicholas Hurt  2 , Sarah Gwynne  3 , David Sebag-Montefiore  4 , Ganesh Radhakrishna  5 , Simon Gollins  6 , Maria Hawkins  7 , Heike I Grabsch  8 , Gareth Jones  9 , Stephen Falk  10 , Ricky Sharma  11 , Andrew Bateman  12 , Rajarshi Roy  13 , Ruby Ray  14 , Jo Canham  15 , Gareth Griffiths  16 , Tim Maughan  17 , Tom Crosby  18
Affiliations
Clinical Trial

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

Somnath Mukherjee et al. Eur J Cancer. 2017 Mar.

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.

Keywords: Chemotherapy; Neo-adjuvant; Oesophageal; Radiotherapy; Randomised phase II; Surgery.

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Figures

Fig. 1
Fig. 1
CONSORT flow diagram of trial participants. *Three of the patients allocated to OxCapRT were actually given CarPacRT due to toxicities during induction chemotherapy.
Fig. 2
Fig. 2
Percent of total chemotherapy dose during CRT (n = 85).
See this image and copyright information in PMC

Comment in

References

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