新视野研究：一项关于可切除食管腺癌的随机II期研究，先进行诱导化疗，然后采用基于奥沙利铂/卡培他滨或卡铂/紫杉醇的术前放化疗。
NEOSCOPE: A randomised phase II study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma.
作者信息
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, Crosby Tom
机构信息
CRUK MRC Oxford Institute for Radiation Oncology Gray Laboratories, Oxford University, Oxford, OX3 7DQ, UK.
Centre for Trials Research, Cardiff University, 6th Floor, Neuadd Meirionnydd, Heath Park, Cardiff, CF14 4YS, UK.
出版信息
Eur J Cancer. 2017 Mar;74:38-46. doi: 10.1016/j.ejca.2016.11.031. Epub 2017 Feb 8.
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 day 1, 15, 29; capecitabine 625 mg/m bd on days of radiotherapy) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m 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 day 1, capecitabine 625 mg/m 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.
背景
基于奥沙利铂 - 卡培他滨（OxCap）和卡铂 - 紫杉醇（CarPac）的新辅助放化疗（nCRT）在局部可切除食管癌中显示出有前景的活性。
患者与方法
一项非盲、随机（通过中央计算机系统按1:1）的“选择优胜者”II期试验。可切除的食管腺癌≥cT3和/或≥cN1的患者被随机分为OxCapRT组（奥沙利铂85mg/m²第1、15、29天；卡培他滨625mg/m²在放疗日每日两次）或CarPacRT组（卡铂AUC2；紫杉醇50mg/m²第1、8、15、22、29天）。放疗剂量为45Gy/25次分割/5周。两组均接受诱导性OxCap化疗（2个3周周期的奥沙利铂130mg/m²第1天，卡培他滨625mg/m²第1 - 21天每日两次）。nCRT后6 - 8周进行手术。主要终点是病理完全缓解（pCR）。次要终点包括毒性、手术并发症/死亡率、切除率和总生存期。
统计学
基于pCR≤15%不值得进一步研究，但pCR≥35%则值得，76例患者（每组38例）有90%的检验效能（单侧α为10%），这意味着在前38例患者中pCR≥10例的组可考虑进行III期试验。ClinicalTrials.gov注册号：NCT01843829。资助者：英国癌症研究中心（C44694/A14614）。
结果
2013年10月至2015年2月期间，来自英国17个中心的85例患者被随机分组。85例中有3例（3.5%）在诱导化疗期间死亡。77例患者（OxCapRT组 = 36例；CarPacRT组 = 41例）接受了手术。术后30天死亡率为2/77（2.6%）。两组间III/IV级毒性相当，尽管CarPacRT组的中性粒细胞减少更高（21.4%对2.6%，p = 0.01）。CarPacRT组和OxCapRT组分别有41例中的12例（29.3%）（前38例患者中的10例）和36例中的4例（11.1%）达到pCR。相应的R0切除率分别为33/41（80.5%）和26/36（72.2%）。
结论
两种方案耐受性均良好。只有CarPacRT组通过了预定义的pCR标准可进行进一步研究。
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