Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: Phase III trial results
Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: Phase III trial results
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DOI：
10.1200/jco.2002.09.002
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发表时间：
2002-06-15
影响因子：
45.3
通讯作者：
Leonard, R
中科院分区：
文献类型：
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作者：
O'Shaughnessy, J;Miles, D;Leonard, R
目的：在临床前研究中，多西他赛和口服氟嘧啶卡培他滨在转移性乳腺癌（MBC）中显示出较高的单药疗效和协同作用。这项国际III期试验比较了卡培他滨/多西紫杉醇治疗与单药多西紫杉醇治疗在蒽环类药物预处理的MBC患者中的疗效和耐受性。患者和方法：患者随机分为21天的周期，第1至14天口服卡培他滨1,250 mg/m(2)，每日两次，第1天加多西他赛75 mg/m(2) （n = 255）或第1天加多西他赛100 mg/m(2) （n = 256）。结果：卡培他滨/多西他赛在疾病进展时间（TTP）（风险比为0.652；95%可信区间[CI]为0.545 ~ 0.780;P = 0.0001；中位数，6.1 v 4.2个月）、总生存期（风险比为0.775；95% CI为0.634 ~ 0.947;P = 0.0126；中位数，14.5 v 11.5个月）和客观肿瘤缓解率（42% v 300%, P = 0.006）方面均显著优于多西他赛。胃肠道副作用和手足综合征在联合治疗中更常见，而肌痛、关节痛和中性粒细胞减少热/败血症在单药多西他赛中更常见。联合治疗的3级不良事件发生率更高（分别为71%和49%），而多西他赛的4级不良事件发生率略高（分别为31%和25%）。结论：在多西他赛75 mg/m(2)中添加卡培他滨获得的TTP和生存期显著优于单药多西他赛100 mg/m(2)，并且毒性谱可控，表明该组合比单药多西他赛有明显的益处。多西他赛/卡培他滨治疗是蒽环类药物预处理MBC妇女的重要治疗选择。
Purpose: Docetaxel and capecitabine, a tumor-activated oral fluoropyrimidine, show high single-agent efficacy in metastatic breast cancer (MBC) and synergy in preclinical studies. This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC.Patients and Methods: Patients were randomized to 21-day cycles of oral capecitabine 1,250 mg/m(2) twice daily on days 1 to 14 plus docetaxel 75 mg/m(2) on day 1 (n = 255) or to docetaxel 100 mg/m(2) on day 1 (n = 256).Results: Capecitabine/docetaxel resulted in significantly superior efficacy in time to disease progression (TTP) (hazard ratio, 0.652; 95% confidence interval [CI], 0.545 to 0.780; P = .0001; median, 6.1 v 4.2 months), overall survival (hazard ratio, 0.775; 95% CI, 0.634 to 0.947; P = .0126; median, 14.5 v 11.5 months), and objective tumor response rate (42% v 300%, P = .006) compared with docetaxel. Gastrointestinal side effects and hand-foot syndrome were more common with combination therapy, whereas myalgia, arthralgia, and neutropenic fever/sepsis were more common with single-agent docetaxel. More grade 3 adverse events occurred with combination therapy (71% v 49%, respectively), whereas grade 4 events were slightly more common with docetaxel (31% v 25% with combination).Conclusion: The significantly superior TTP and survival achieved with the addition of capecitabine to docetaxel 75 mg/m(2), with the manageable toxicity profile, indicate that this combination provides clear benefits over single-agent docetaxel 100 mg/m(2). Docetaxel/capecitabine therapy is an important treatment option for women with anthracycline-pretreated MBC.