Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial.
Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial.
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对结直肠癌的可切除肝转移的FOLFOX4和手术的围手术性化疗（EORTC组间试验40983）：一项随机对照试验。
DOI：
10.1016/s0140-6736(08)60455-9
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发表时间：
2008-03-22
期刊：
影响因子：
168.9
通讯作者：
Gruenberger, Thomas
中科院分区：
文献类型：
--
作者：
Nordlinger, Bernard;Sorbye, Halfdan;Glimelius, Bengt;Poston, Graeme J.;Schlag, Peter M.;Rougier, Philippe;Bechstein, Wolf O.;Primrose, John N.;Euan, T. Walpole;Finch-Jones, Meg;Jaeck, Daniel;Mirza, Darius;Parks, Rowan W.;Collette, Laurence;Praet, Michel;Bethe, Ullrich;Van Cutsem, Eric;Scheithauer, Werner;Gruenberger, Thomas
对于结直肠癌肝转移患者，单纯手术切除被视为标准治疗方法，但复发很常见。我们评估了围手术期化疗联合手术与单纯手术对初始可切除的结直肠癌肝转移患者的疗效。
这项平行组研究报告了该试验在方案未明确的中期时间点的无进展生存期的最终数据，而总生存期仍在监测中。364例经组织学证实患有结直肠癌且肝转移灶不超过4个的患者被随机分配到术前和术后各6个周期的FOLFOX4化疗组或单纯手术组（围手术期化疗组182例，手术组182例）。通过最小化方法进行中心随机分组，并根据中心和风险评分进行调整。主要目的是检测无进展生存期的风险比（HR）是否为0.71或更低。主要分析采用意向性治疗分析。对所有符合条件的患者（171例对171例）和接受切除手术的患者（151例对152例）重复进行分析。该试验已在ClinicalTrials.gov注册，注册号为NCT00006479。
在围手术期化疗组，151例（83%）患者在中位6个周期（范围1 - 6个）术前化疗后接受了手术切除，115例（63%）患者接受了中位6个周期（1 - 8个）的术后化疗。手术组有152例（84%）患者接受了手术切除。随机分组患者3年无进展生存率的绝对提高率为7.3%（从28.1%[95.66%置信区间21.3 - 35.5]提高到35.4%[28.1 - 42.7]；风险比0.79[0.62 - 1.02]；p = 0.058）；符合条件的患者为8.1%（从28.1%[21.2 - 36.6]提高到36.2%[28.7 - 43.8]；风险比0.77[0.60 - 1.00]；p = 0.041）；接受切除手术的患者为9.2%（从33.2%[25.3 - 41.2]提高到42.4%[34.0 - 50.5]；风险比0.73[0.55 - 0.97]；p = 0.025）。139例患者死亡（围手术期化疗组64例，手术组75例）。化疗后可逆性术后并发症的发生率高于手术组（40/159[25%]对27/170[16%]；p = 0.04）。手术后，单纯手术组有2例死亡，围手术期化疗组有1例死亡。
FOLFOX4围手术期化疗与肝脏大手术是相容的，并且降低了符合条件和接受切除手术患者的无进展生存期事件风险。
瑞典癌症协会、英国癌症研究中心、法国国家癌症防治联盟、美国国家癌症研究所、赛诺菲 - 安万特公司。
Surgical resection alone is regarded as the standard of care for patients with liver metastases from colorectal cancer, but relapse is common. We assessed the combination of perioperative chemotherapy and surgery compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. This parallel-group study reports the trial's final data for progression-free survival for a protocol unspecified interim time-point, while overall survival is still being monitored. 364 patients with histologically proven colorectal cancer and up to four liver metastases were randomly assigned to either six cycles of FOLFOX4 before and six cycles after surgery or to surgery alone (182 in perioperative chemotherapy group vs 182 in surgery group). Patients were centrally randomised by minimisation, adjusting for centre and risk score. The primary objective was to detect a hazard ratio (HR) of 0·71 or less for progression-free survival. Primary analysis was by intention to treat. Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152). This trial is registered with ClinicalTrials.gov, number NCT00006479. In the perioperative chemotherapy group, 151 (83%) patients were resected after a median of six (range 1–6) preoperative cycles and 115 (63%) patients received a median six (1–8) postoperative cycles. 152 (84%) patients were resected in the surgery group. The absolute increase in rate of progression-free survival at 3 years was 7·3% (from 28·1% [95·66% CI 21·3–35·5] to 35·4% [28·1–42·7]; HR 0·79 [0·62–1·02]; p=0·058) in randomised patients; 8·1% (from 28·1% [21·2–36·6] to 36·2% [28·7–43·8]; HR 0·77 [0·60–1·00]; p=0·041) in eligible patients; and 9·2% (from 33·2% [25·3–41·2] to 42·4% [34·0–50·5]; HR 0·73 [0·55–0·97]; p=0·025) in patients undergoing resection. 139 patients died (64 in perioperative chemotherapy group vs 75 in surgery group). Reversible postoperative complications occurred more often after chemotherapy than after surgery (40/159 [25%] vs 27/170 [16%]; p=0·04). After surgery we recorded two deaths in the surgery alone group and one in the perioperative chemotherapy group. Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients. Swedish Cancer Society, Cancer Research UK, Ligue Nationale Contre le Cancer, US National Cancer Institute, Sanofi-Aventis.