Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer
Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer
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DOI：
10.1200/jco.2007.14.9898
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发表时间：
2008-04-20
影响因子：
45.3
通讯作者：
Saltz, Leonard
中科院分区：
文献类型：
--
作者：
Cassidy, Jim;Clarke, Stephen;Saltz, Leonard
目的评价卡培他滨联合奥沙利铂(XELOX)方案是否不亚于氟尿嘧啶。亚叶酸和奥沙利铂(FOLFOX-4)作为转移性结直肠癌(MCRC)的一线治疗。患者和方法这项试验的初始设计是XELOX和FOLFOX-4的随机、双臂、非劣质、III期比较。在患者开始应计后，试验设计在2003年贝伐单抗III期数据可用后进行了修改。由此产生的2×2析因设计将患者随机分配到XELOX和FOLFOX-4，然后也接受贝伐单抗或安慰剂。我们在这里报告了XELOX和FOLFOX-4武器的分析结果。贝伐单抗与安慰剂联合奥沙利铂化疗的分析分别报道。非劣势分析的预先指定的主要终点是无进展生存。结果意向治疗人群包括634名来自研究的原始双臂部分的患者，加上在修订的2×2设计开始后的1400名患者，总计2,034名患者。合并使用XELOX的中位PFS为8.0个月，而使用FOLFOX-4的中位PFS为8.5个月(危险比[HR]，1.04；97.5%CI，0.93比1.16)。XELOX组的中位总生存期为19.8个月，FOLFOX-4组的中位生存期为19.6个月(HR，0.99；97.5%CI，0.88~1.12)。FOLFOX-4与XELOX相比有更多的3/4级中性粒细胞减少/粒细胞减少症和发热中性粒细胞减少症，XELOX比FOLFOX-4有更多的3级腹泻和3级手足综合征。结论XELOX作为MCRC的一线治疗方案并不逊色于FOLFOX-4，可作为合适患者的常规治疗方案。
PurposeTo evaluate whether capecitabine plus oxaliplatin (XELOX) is noninferior to fluorouracil. folinic acid, and oxaliplatin (FOLFOX-4) as first-line therapy in metastatic colorectal cancer (MCRC).Patients and MethodsThe initial design of this trial was a randomized, two-arm, noninferiority, phase III comparison of XELOX versus FOLFOX-4. After patient accrual had begun, the trial design was amended in 2003 after bevacizumab phase III data became available. The resulting 2 x 2 factorial design randomly assigned patients to XELOX versus FOLFOX-4, and then to also receive either bevacizumab or placebo. We report here the results of the analysis of the XELOX versus FOLFOX-4 arms. The analysis of bevacizumab versus placebo with oxaliplatin-based chemotherapy is reported separately. The prespecified primary end point for the noninferiority analysis was progression-free survival.ResultsThe intent-to-treat population comprised 634 patients from the original two-arm portion of the study, plus an additional 1,400 patients after the start of the amended 2 x 2 design, for a total of 2,034 patients. The median PFS was 8.0 months in the pooled XELOX-containing arms versus 8.5 months in the FOLFOX-4-containing arms (hazard ratio [HR], 1.04; 97.5% CI, 0.93 to 1.16). The median overall survival was 19.8 months with XELOX versus 19.6 months with FOLFOX-4 (HR, 0.99; 97.5% CI, 0.88 to 1.12). FOLFOX-4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhea and grade 3 hand-foot syndrome than FOLFOX-4.ConclusionXELOX is noninferior to FOLFOX-4 as a first-line treatment for MCRC, and may be considered as a routine treatment option for appropriate patients.