Abstract
BackgroundOxaliplatin-capecitabine (OxCap) and carboplatin-paclitaxel (CarPac) based neo-adjuvant chemoradiotherapy (nCRT) have shown promising activity in localised, resectable oesophageal cancer. Patients and methodsA 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. StatisticsBased 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). ResultsEighty 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. ConclusionBoth regimens were well tolerated. Only CarPacRT passed the predefined pCR criteria for further investigation.
Highlights
Treatment by surgery alone confers poor outcome in patients with resectable oesophageal cancer
Neutropenia during CRT was significantly higher in the carboplatin-paclitaxel arm (21.4% versus 2.6%, p Z 0.01), this did not translate into increased risk of mortality
This study demonstrated, through the use of a detailed protocol and robust quality assurance programme, the safety and feasibility of introducing Neoadjuvant chemoradiotherapy (nCRT) into clinical practice in the United Kingdom
Summary
Treatment by surgery alone confers poor outcome in patients with resectable oesophageal cancer. Neoadjuvant chemoradiotherapy (nCRT) preceding surgery improves disease-specific survival. Efforts to improve these outcomes have focussed on the addition of adjuvant chemotherapy and/or radiotherapy to surgical treatment. Most of the randomised studies evaluating nCRT were performed over two decades ago, were heterogenous in design, often underpowered, largely tested platinum/fluropyrimidine-based regimens, and reported a high incidence of treatmentrelated toxicity and post-operative mortality [1]. Pac) based neo-adjuvant chemoradiotherapy (nCRT) have shown promising activity in localised, resectable oesophageal cancer. Radiotherapy dose was 45 Gy/25 fractions/5 weeks Both arms received induction OxCap chemotherapy (2 Â 3 week cycles of oxaliplatin 130 mg/m2 day 1, capecitabine 625 mg/m2 bd days 1e21). Secondary end-points included toxicity, surgical morbidity/mortality, resection rate and overall survival. Results: Eighty five patients were randomised between October 2013 and February 2015 from
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