Fluorouracil, Leucovorin, and Irinotecan Plus Either Sunitinib or Placebo in Metastatic Colorectal Cancer: A Randomized, Phase III Trial
Fluorouracil, Leucovorin, and Irinotecan Plus Either Sunitinib or Placebo in Metastatic Colorectal Cancer: A Randomized, Phase III Trial
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DOI：
10.1200/jco.2012.45.1930
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发表时间：
2013-04-01
影响因子：
45.3
通讯作者：
Van Cutsem, Eric
中科院分区：
文献类型：
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作者：
Carrato, Alfredo;Swieboda-Sadlej, Anna;Van Cutsem, Eric
目的：本双盲、III期临床研究旨在证明舒尼替尼联合FOLFIRI方案在既往未经治疗的转移性结直肠癌（mCRC）中，氟尿嘧啶、亚叶酸钙和伊立替康（fluorouracil，leucovorin，and irinotecan）优于安慰剂加FOLFIRI的上级效果。（37.5 mg/天）或安慰剂（治疗4周，随后停药2周[方案4/2]）直至疾病进展。主要终点是无进展生存期（PFS）。次要终点包括总生存期、安全性和患者报告的结局。基因型和临床outcomes.ResultsIn所有，768例患者被随机分配到舒尼替尼加FOLFIRI（n = 386）或安慰剂加FOLFIRI（n = 382）之间的相关性进行了分析。在第二次预先规定的中期分析后，由于舒尼替尼联合FOLFIRI的潜在无效性，研究停止。报告了最终结果。PFS风险比为1.095（95% CI，0.892 - 1.344;单侧分层对数秩P = 0.807），表明舒尼替尼联合FOLFIRI缺乏优效性。舒尼替尼组的中位PFS为7.8个月（95% CI，7.1 - 8.4个月）vs 8.4个月舒尼替尼联合FOLFIRI与安慰剂组相比，与更多≥ 3级不良事件和实验室异常相关（95%CI，7.6 - 9.2个月）。（尤其是腹泻、口腔炎/口腔综合征、疲劳、手足综合征、中性粒细胞减少症、血小板减少症、贫血和发热性中性粒细胞减少症）。更多的死亡，由于毒性（12 V 4）和显着更多的剂量延迟，剂量减少，治疗中止发生在sunitinib arm.ConclusionSunitinib 37.5 mg/天（时间表4/2）加FOLFIRI是不是上级FOLFIRI单独和具有较差的安全性。不推荐这种联合方案用于既往未经治疗的mCRC。J Clin Oncol 31：1341-1347. (C)2013年美国临床肿瘤学会
PurposeThis double-blind, phase III study aimed to demonstrate that sunitinib plus FOLFIRI (fluorouracil, leucovorin, and irinotecan) was superior to placebo plus FOLFIRI in previously untreated metastatic colorectal cancer (mCRC).Patients and MethodsPatients were randomly assigned to receive FOLFIRI and either sunitinib (37.5 mg per day) or placebo (4 weeks on treatment, followed by 2 weeks off [schedule 4/2]) until disease progression. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, safety, and patient-reported outcomes. The correlation between genotype and clinical outcomes was also analyzed.ResultsIn all, 768 patients were randomly assigned to sunitinib plus FOLFIRI (n = 386) or placebo plus FOLFIRI (n = 382). Following a second prespecified interim analysis, the study was stopped because of potential futility of sunitinib plus FOLFIRI. Final results are reported. The PFS hazard ratio was 1.095 (95% CI, 0.892 to 1.344; one-sided stratified log-rank P = .807), indicating a lack of superiority for sunitinib plus FOLFIRI. Median PFS for the sunitinib arm was 7.8 months (95% CI, 7.1 to 8.4 months) versus 8.4 months (95% CI, 7.6 to 9.2 months) for the placebo arm. Sunitinib plus FOLFIRI was associated with more grade >= 3 adverse events and laboratory abnormalities than placebo (especially diarrhea, stomatitis/oral syndromes, fatigue, hand-foot syndrome, neutropenia, thrombocytopenia, anemia, and febrile neutropenia). More deaths as a result of toxicity (12 v four) and significantly more dose delays, dose reductions, and treatment discontinuations occurred in the sunitinib arm.ConclusionSunitinib 37.5 mg per day (schedule 4/2) plus FOLFIRI is not superior to FOLFIRI alone and has a poorer safety profile. This combination regimen is not recommended for previously untreated mCRC. J Clin Oncol 31:1341-1347. (C) 2013 by American Society of Clinical Oncology