Oxaliplatin plus irinotecan compared with irinotecan alone as second-line treatment after single-agent fluoropyrimidine therapy for metastatic colorectal carcinoma
Oxaliplatin plus irinotecan compared with irinotecan alone as second-line treatment after single-agent fluoropyrimidine therapy for metastatic colorectal carcinoma
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DOI：
10.1200/jco.2008.17.1249
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发表时间：
2008-10-01
影响因子：
45.3
通讯作者：
Olivatto, Luis O.
中科院分区：
文献类型：
--
作者：
Haller, Daniel G.;Rothenberg, Mace L.;Olivatto, Luis O.
目的探讨伊立替康联合奥沙利铂（IROX）治疗转移性结直肠癌（CRC）是否优于伊立替康单用氟嘧啶单药治疗。患者和方法：一项III期、随机、开放标签、多中心研究，研究对象是在辅助治疗或一线氟嘧啶治疗期间或之后进展或复发的转移性或复发性结直肠癌患者（氟尿嘧啶/亚叶酸钙或卡培他滨，后者仅用于转移性结直肠癌）。患者每3周接受IROX治疗(伊立替康200 mg/m（2) +奥沙利铂85 mg/m（2)）或单独伊立替康350 mg/m(2)）。结果在数据截止时（628例随机分配的患者中有447例死亡），IROX组和伊立替康组的中位总生存期分别为13.4个月（95% CI, 12.4 ~ 14.7个月）和11.1个月（95% CI, 10.0 ~ 12.7个月）（风险比= 0.78;95% CI, 0.65 ~ 0.94; P = 0.0072）。与伊立替康相比，IROX的总缓解率（分别为22% v 7%， P < 0.0001）、中位进展时间（分别为5.3 v 2.8个月，P < 0.0001）和肿瘤相关症状的改善（分别为32% v 19%， P < 0.0072）也得到改善。除了粒细胞减少症（25% vs 13%）、腹泻（28% vs 23%）和感觉障碍（5% vs 0%）外，IROX组和伊立替康组的3 - 4级毒性分别相当。结论irox是一线氟嘧啶治疗后进展的转移性结直肠癌的有效治疗方法。与单独使用伊立替康相比，IROX提高了疗效，为单药氟嘧啶治疗失败的患者提供了辅助后或二线治疗的额外选择。
PurposeTo determine whether irinotecan plus oxaliplatin (IROX) is superior to irinotecan alone in patients with metastatic colorectal cancer (CRC) previously treated with single-agent fluoropyrimidines.Patients and MethodsA phase III, randomized, open-label, multicenter study of patients with metastatic or recurrent CRC that had progressed or recurred during or after adjuvant or first-line fluoropyrimidines (fluorouracil/leucovorin or capecitabine, the latter only for metastatic CRC). Patients received IROX (irinotecan 200 mg/m(2) plus oxaliplatin 85 mg/m(2)) or irinotecan alone (350 mg/m(2)) every 3 weeks.ResultsAt the data cutoff (when 447 of 628 randomly assigned patients had died), median overall survival was 13.4 months (95% CI, 12.4 to 14.7 months) and 11.1 month (95% CI, 10.0 to 12.7 months) in the IROX and irinotecan groups, respectively (hazard ratio = 0.78; 95% CI, 0.65 to 0.94; P = .0072). Overall response rate (22% v 7%, respectively; P < .0001), median time to progression (5.3 v 2.8 months, respectively; P < .0001), and improvement in tumor-related symptoms (32% v 19%, respectively; P < .0072) were also improved with IROX as compared with irinotecan. With the exception of granulocytopenia (25% v 13%), diarrhea (28% v 23%), and sensory disturbances (5% v 0%), grade 3 to 4 toxicities were comparable between the IROX and irinotecan groups, respectively.ConclusionIROX is an effective treatment for metastatic CRC that has progressed after first-line fluoropyrimidine therapy. IROX improves efficacy compared with irinotecan alone, providing an additional option in the postadjuvant or second-line treatment setting for patients who experience treatment failure with single-agent fluoropyrimidine therapy.