Efficacy of Oxaliplatin Plus Capecitabine or Infusional Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer: A Pooled Analysis of Randomized Trials
Efficacy of Oxaliplatin Plus Capecitabine or Infusional Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancer: A Pooled Analysis of Randomized Trials
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DOI：
10.1200/jco.2008.16.7759
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发表时间：
2008-12-20
影响因子：
45.3
通讯作者：
Porschen, Rainer
中科院分区：
文献类型：
--
作者：
Arkenau, Hendrik-Tobias;Arnold, Dirk;Porschen, Rainer
目的6项随机II期和III期临床试验研究了奥沙利铂（OX）联合卡培他滨（CAP）或氟尿嘧啶（FU）治疗转移性结直肠癌的作用。这项荟萃分析比较了CAP/OX的疗效与输液FU/OX.Patients和MethodsThis分析比较了所有出版的CAP/OX与输液FU/OX方案。共计3,494名患者（FU，n = 1，737; CAP，n = 1，757）分析反应率（RR）、无进展（PFS）、总生存期（OS）和毒性。（比值比[ OR] = 0.85; 95%CI，0.74 - 0.97; P = 0.02），而仅化疗试验的分析（不包括含贝伐单抗的NO16966和TREE 2试验）得出的OR为0.74（95%CI，0.60 - 0.92; P = 0.007）。然而，对于PFS（风险比[ HR] = 1.04; 95% CI，0.96 - 1.12; P = 0.17）和OS（HR = 1.04; 95% CI，0.95 - 1.12; P = 0.41），所有模型均表明在非劣效性范围内结局相似。3/4级毒性（血小板减少症-HR = 2.07，95% CI，1.42至3.03; P < .0002;血小板减少症-HR = 1.34; 95% CI，1.08至1.66; P < .0009; 2/3级手足综合征[ HFS]-HR = 3.54; 95% CI，2.07至6.05; P < .00001）在FU为基础的治疗方案中不太突出，而在CAP治疗方案中中性粒细胞减少（HR = 0.15; 95%CI，0.11至0.19; P < .00001）较低。毒性分析显示了每种不同FU方案的特征性毒性，血小板减少症和HFS在CAP方案中始终更突出。
PurposeSix randomized phase II and III trials have investigated the role of oxaliplatin ( OX) in combination with capecitabine ( CAP) or infusional fluorouracil ( FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX.Patients and MethodsThis analysis compared all published CAP/OX versus infusional FU/OX regimens. A total of 3,494 patients ( FU, n = 1,737; CAP, n = 1,757) were analyzed for response rate ( RR), progression-free ( PFS), overall survival ( OS), and toxicity.ResultsThe fixed-effect pooled estimate for RR showed higher RR for FU-based regimens ( Odds ratio [ OR] = 0.85; 95% CI, 0.74 to 0.97; P = .02) whereas the analysis of chemotherapy-only trials, excluding the bevacizumab containing NO16966 and TREE 2 trials, led to an OR of 0.74 ( 95% CI, 0.60 to 0.92; P = .007). However, for PFS ( hazard ratio [ HR] = 1.04; 95% CI, 0.96 to 1.12; P = .17) and OS ( HR = 1.04; 95% CI, 0.95 to 1.12; P = .41) all models suggested similar outcome within the range of noninferiority. Grade 3/4 toxicities ( thrombocytopenia -HR = 2.07, 95% CI, 1.42 to 3.03; P < .0002; diarrhea-HR = 1.34; 95% CI, 1.08 to 1.66; P < .0009; and grade 2/3 hand-foot-syndrome [ HFS]-HR = 3.54; 95% CI, 2.07 to 6.05; P < .00001) were less prominent with FU-based regimens whereas neutropenia ( HR = 0.15; 95% CI, 0.11 to 0.19; P < .00001) was lower in the CAP regimens.ConclusionThe combination of CAP and OX resulted in lower RR, but this did not affect PFS and OS, which were similar in both treatment arms. The toxicity analysis showed the characteristic toxicity of each of the different FU schedules, with thrombocytopenia and HFS consistently more prominent in the CAP regimens.