Ixabepilone in combination with capecitabine and as monotherapy for treatment of advanced breast cancer refractory to previous chemotherapies
Ixabepilone in combination with capecitabine and as monotherapy for treatment of advanced breast cancer refractory to previous chemotherapies
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DOI：
10.1158/1078-0432.ccr-08-0015
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发表时间：
2008-07-15
影响因子：
11.5
通讯作者：
Pazdur, Richard
中科院分区：
文献类型：
--
作者：
Lechleider, Robert J.;Kaminskas, Edvardas;Pazdur, Richard
目的：描述导致伊克沙比隆与卡培他滨联合以及作为单一疗法用于对其他化疗药物无效的晚期乳腺癌的上市批准的考虑因素。实验设计：对一项随机多中心试验的数据进行分析，比较联合疗法与卡培他滨和单用卡培他滨的疗效。对于单一疗法，分析了伊克沙比隆的单臂试验。结果：与单用卡培他滨相比，转移性或局部晚期乳腺癌患者服用或服用了蒽环类药物和紫杉烷后，无进展生存期明显改善(分层对数等级P<；0.0001；无进展生存率中位数为5.7[95%可信区间(95%CI)，4.8-6.7]；危险比，0.69(95%可信区间，0.58-0.83)}。作为服用或跟随服用或服用了蒽环类药物、紫杉烷和卡培他滨而病情恶化的患者的单一疗法，ixabpione作为单一疗法，通过独立盲法审查和研究者评估，显示出12%的客观应答率和18%的客观应答率。结论：2007年10月16日，美国食品药品监督管理局批准注射用伊克沙比隆与卡培他滨联合或作为单药治疗既往化疗后病情进展的晚期乳腺癌患者。
Purpose: To describe the considerations leading to marketing approval of ixabepilone in combination with capecitabine and as monotherapy for the treatment of advanced breast cancer that is refractory to other chemotherapies.Experimental Design: Data from one randomized multicenter trial comparing combination therapy with ixabepilone and capecitabine to capecitabine alone were analyzed for support of the combination therapy indication. For monotherapy, a single-arm trial of ixabepilone was analyzed. Supporting data came from an additional single-arm combination therapy study and two single-arm monotherapy studies.Results: In patients with metastatic or locally advanced breast cancer who had disease progression on or following an anthracycline and a taxane, ixabepilone plus capecitabine showed an improvement in progression-free survival compared with capecitabine alone {median progression-free survival, 5.7 [95% confidence interval (95% CI), 4.8-6.7] versus 4.1 (95% CI, 3.1-4.3) months, stratified log-rank P < 0.0001; hazard ratio, 0.69 (95% CI, 0.58-0.83)}. As monotherapy for patients who had disease progression on or following an anthracycline, a taxane, and capecitabine, ixabepilone as monotherapy showed a 12% objective response rate by independent blinded review and 18% by investigator assessment. The major toxicities from ixabepilone therapy were peripheral neuropathy and myelosuppression, particularly neutropenia.Conclusions: On October 16, 2007, the Food and Drug Administration approved ixabepilone for injection in combination with capecitabine or as monotherapy for the treatment of patients with advanced breast cancer who have experienced disease progression on previous chemotherapies.