医脉通编译，转载请务必注明出处
2015年ASCO年会于5月29日—6月2日在美国芝加哥召开。5月31日上午的消化系统（非结直肠）肿瘤口头报告专场上，来自英国医学研究委员会OEO5随机试验（ISRCTN 01852072）的研究结果揭示了可切除食管和交界区腺癌患者接受新辅助化疗的情况。医脉通整理如下：
新辅助化疗（2个周期顺铂/5-氟尿嘧啶）（CF）序贯手术治疗是局部晚期食管癌的标准治疗方案。该项研究探讨了增加化疗周期数（4个周期表柔比星/顺铂/卡培他滨（ECX））是否会带来患者预后的改善。
该项研究是一项多中心随机III期临床试验，将2个周期CF化疗与4个周期ECX化疗序贯食管切除术的疗效进行比较，其中低位和交界区腺癌（I型和II型）联合了2区淋巴结清扫。主要终点是总生存期（OS）；预期入组842例患者（677例死亡），预计3年存活率提高至82%（或70%），提升幅度为30%至38%（或37%），检验效能为2α=5%。死亡病例累计未达到预期值，但独立数据监测委员会认为该数据足够充分，结果可以发布。次要预后包括无病生存期（DFS），无进展生存期（PFS），病理R0切除率，Mandard分级，和生活质量。
2005至2011年，英国72个中心入组897例（CF：451例，ECX：446例），按照1:1随机分配。两组间的基线特征类似（总体，男性90%，中位年龄62岁[四分位数间距56-67]，60%的PET检查，分期T3 N0占22%、T3 N1占65%）。CF组96%的患者接受了2个周期化疗，ECX组89%的患者接受了3个周期以上化疗。
CF组3/4级毒副反应的发生率较低（30% vs 47%，P＜0.001）。本研究R0切除率CF组为60%，ECX组为66%；Mandard分级≤3级的发生率CF组15%，而ECX组可达到32%，其中有3例约11%患者达到完全缓解。两组术后并发症的发生率相似（CF：57%，ECX：62%），术后30天（CF：2%，ECX：2%），术后90天（CF：4%，ECX：5%）。ECX组在PFS和DFS上更有优势，危险比（HR，95%CI）PFS 0.86（0.74-1.01），DFS 0.88（0.75-1.03）。CF组315例死亡，ECX组298例死亡，两组OS的HR值为0.92（0.79-1.08，P=0.3017），两组的3年生存率差异较小CF 39%（35-44%）vs ECX 42%（37-46%）。
通过试验发现，延长的ECX方案在PFS，DFS和肿瘤消退上有一定优势，但未转化为生存获益。相比于2个周期CF化疗，4个周期ECX化疗的总化疗毒副反应发生率提高，但手术并发症未见增加。临床试验信息：01852072。
会议专题》》》2015年ASCO年会专题报道
阅读原文摘要
Neoadjuvant chemotherapy for resectable oesophageal and junctional adenocarcinoma: Results from the UK Medical Research Council randomised OEO5 trial (ISRCTN 01852072).（Abstract 4002）
Authors：Derek Alderson, Ruth E Langley,et al.
Session Type：Oral Abstract Session
Background：Neoadjuvant chemotherapy (2 cycles cisplatin/5 fluorouracil) (CF) followed by surgery is a standard of care for locally advanced oesophageal cancer. We investigated whether more chemotherapy (4 cycles epirubicin/cisplatin /capecitabine (ECX)) would improve outcomes.
Methods：A multi-centre, randomised, phase III trial comparing 2 cycles of CF with 4 cycles of ECX followed by oesophagectomy with 2-field lymphadenectomy for lower oesophageal and junctional (Types I and II) adenocarcinoma. Primary outcome was overall survival (OS); 842 patients (677 deaths) would detect an increase in 3-year survival from 30% to 38% (or 37%) with 82% (or 70%) power with 2α = 5%. Deaths accrued more slowly than anticipated but the Independent Data Monitoring Committee considered the data sufficiently robust for release. Secondary outcomes include disease-free (DFS) and progression-free survival (PFS), pathological R0 resection rate, Mandard grade and quality of life.
Results：From 2005-2011, 897 patients (451 CF, 446 ECX) from 72 UK centres were randomly allocated (1:1). Baseline characteristics were similar between the groups (overall, male 90%, median age 62 (IQR 56-67), staging included PET 60%, T3 N0 22%, T3 N1 65%). 96% CF received 2 cycles, 89% ECX > 3 cycles. Grade 3/4 toxicity was lower with CF (30% v 47% p < 0.001.) Of those patients having a resection R0 rates were CF 60%, ECX 66% with a Mandard grade ≤ 3 achieved in CF 15% v ECX 32% with 3 and 11% achieving complete response. Post-operative complications were similar (CF 57%, ECX 62%) as were deaths at 30 (CF 2%, ECX 2%) and 90 days post-surgery (CF 4%, ECX 5%). PFS and DFS favoured ECX, hazard ratio (HR, 95% CI) PFS 0.86 (0.74-1.01), DFS 0.88 (0.75-1.03). HR for OS was 0.92 (0.79-1.08, p = 0.3017) based on 315 CF and 298 ECX deaths, with similar 3 year survival rates CF 39% (35-44%) vs ECX 42% (37-46%).
Conclusions：There is some evidence of a benefit from the prolonged ECX regimen, in terms of PFS, DFS and tumour regression at resection, but this does not translate into a survival benefit. Overall chemotherapy toxicity was higher with 4 cycles of ECX compared to 2 cycles of CF but surgical morbidity was not increased. Clinical trial information: 01852072.
