Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial
Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial
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DOI：
10.1016/s1470-2045(14)70028-2
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发表时间：
2014-03-01
期刊：
影响因子：
51.1
通讯作者：
Adenis, Antoine
中科院分区：
文献类型：
--
作者：
Conroy, Thierry;Galais, Marie-Pierre;Adenis, Antoine
背景：明确的放化疗是食管癌的一种治疗选择，特别是对不适合手术的患者。PRODIGE5/ACCORD17试验旨在评估FOLFOX治疗方案（氟尿嘧啶+亚叶酸钙和奥沙利铂）与氟尿嘧啶+顺铂作为局部食管癌患者放化疗的一部分的有效性和安全性。方法：2004年10月15日至2011年8月25日，我们在法国24个中心招募了18岁及以上的患者，进行了一项多中心、随机、开放标签、平行组、2/3期试验。符合条件的参与者确认为I-IVA期食管癌（腺癌、鳞状细胞癌或腺鳞癌），东部肿瘤合作组（ECOG）状态0-2，足够的热量摄入，足够的血液学、肾脏和肝功能，并被选中接受明确的放化疗。患者被随机分配（1:1）接受奥沙利铂85 mg/m(2)、亚叶酸钙200 mg/m(2)、氟尿嘧啶400 mg/m(2)、氟尿嘧啶输注1600 mg/m(2) （FOLFOX）的6个周期（3个与放疗同时），或4个周期（2个与放疗同时）氟尿嘧啶1000 mg/m(2)每天4天，顺铂75 mg/m(2)第1天。两组均接受50 Gy放疗，分25次（5次/周）。治疗组的随机分配由中央计算机随机化程序完成，通过最小化，按中心，组织学，体重减轻和ECOG状态分层，并独立于研究人员完成。主要终点为无进展生存期。数据分析主要通过意向治疗进行。本研究已在ClinicalTrials.gov注册，编号NCT00861094。结果：FOLFOX组134例，氟尿嘧啶和顺铂组133例（意向治疗人群），FOLFOX组131例，氟尿嘧啶和顺铂组128例患者实际接受了研究药物（安全人群）。中位随访为25.3个月（IQR为15.9 ~ 36.4）。FOLFOX组的中位无进展生存期为9.7个月（95% CI 8.1-14.5），氟尿嘧啶和顺铂组的中位无进展生存期为9.4个月（8.1-10.6）（HR 0.93, 95% CI 0.70-1.24; p=0.64）。FOLFOX组中毒性死亡1例，氟尿嘧啶-顺铂组中毒性死亡6例（p=0.066）。治疗组之间最常见的3级或4级不良事件发生率无显著差异。在5%或更多患者发生的所有级别不良事件中，FOLFOX组131例患者发生61例（47%）感觉异常事件，而顺铂-氟尿嘧啶组128例患者发生3例（2%）
Background Definitive chemoradiotherapy is a curative treatment option for oesophageal carcinoma, especially in patients unsuitable for surgery. The PRODIGE5/ACCORD17 trial aimed to assess the efficacy and safety of the FOLFOX treatment regimen (fluorouracil plus leucovorin and oxaliplatin) versus fluorouracil and cisplatin as part of chemoradiotherapy in patients with localised oesophageal cancer.Methods We did a multicentre, randomised, open-label, parallel-group, phase 2/3 trial of patients aged 18 years or older enrolled from 24 centres in France between Oct 15, 2004, and Aug 25, 2011. Eligible participants had confirmed stage I-IVA oesophageal carcinoma (adenocarcinoma, squamous-cell, or adenosquamous), Eastern Cooperative Oncology Group (ECOG) status 0-2, sufficient caloric intake, adequate haematological, renal, and hepatic function, and had been selected to receive definitive chemoradiotherapy. Patients were randomly assigned (1: 1) to receive either six cycles (three concomitant to radiotherapy) of oxaliplatin 85 mg/m(2), leucovorin 200 mg/m(2), bolus fluorouracil 400 mg/m(2), and infusional fluorouracil 1600 mg/m(2) (FOLFOX) over 46 h, or four cycles (two concomitant to radiotherapy) of fluorouracil 1000 mg/m(2) per day for 4 days and cisplatin 75 mg/m(2) on day 1. Both groups also received 50 Gy radiotherapy in 25 fractions (five fractions per week). Random allocation to treatment groups was done by a central computerised randomisation procedure by minimisation, stratified by centre, histology, weight loss, and ECOG status, and was achieved independently from the study investigators. The primary endpoint was progression-free survival. Data analysis was primarily done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00861094.Findings 134 participants were randomly allocated to the FOLFOX group and 133 to the fluorouracil and cisplatin group (intention-to-treat population), and 131 patients in the FOLFOX group and 128 in the fluorouracil and cisplatin group actually received the study drugs (safety population). Median follow-up was 25.3 months (IQR 15.9-36.4). Median progression-free survival was 9.7 months (95% CI 8.1-14.5) in the FOLFOX group and 9.4 months (8.1-10.6) in the fluorouracil and cisplatin group (HR 0.93, 95% CI 0.70-1.24; p=0.64). One toxic death occurred in the FOLFOX group and six in the fluorouracil-cisplatin group (p=0.066). No significant differences were recorded in the rates of most frequent grade 3 or 4 adverse events between the treatment groups. Of all-grade adverse events that occurred in 5% or more of patients, paraesthesia (61 [47%] events in 131 patients in the FOLFOX group vs three [2%] in 128 patients in the cisplatin-fluorouracil group, p