Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline: Randomized phase II multicenter trial
Combination of docetaxel and TSU-68, an oral antiangiogenic agent, in patients with metastatic breast cancer previously treated with anthracycline: Randomized phase II multicenter trial
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多西紫杉醇和 TSU-68（一种口服抗血管生成剂）联合治疗既往接受过蒽环类药物治疗的转移性乳腺癌患者：随机 II 期多中心试验
DOI：
10.1007/s10637-014-0093-6
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发表时间：
2014
影响因子：
3.4
通讯作者：
H. Chung
中科院分区：
文献类型：
--
作者：
Sung;C. Yoo;J. Ro;S. Im;Y. Im;J. Kim;J. Ahn;K. Jung;H. Song;S. Kang;H. Park;H. Chung
研究了新型口服抗血管生成药物TSU-68在转移性乳腺癌患者中的作用。蒽环类药物预处理的转移性乳腺癌患者被随机分配接受TSU-68 400 mg，每日2次，第1 - 21天，加多西他赛60 mg/m2，每3周第1天，或多西他赛60 mg/m2，每3周第1天。主要终点为无进展生存期。在2006年11月至2007年12月期间，81例患者被纳入该研究（41例TSU-68联合多西他赛，40例多西他赛单独）。tu -68联合多西他赛组的中位无进展生存期为6.8个月（95%可信区间[CI] = 5.4-12.5个月），而多西他赛单用组的中位无进展生存期为8.1个月（95% CI = 4.0-13.7个月）（风险比[HR] = 1.0; 95% CI = 0.6-1.8; p = 0.95）。两组总有效率和总生存率差异无统计学意义（p = 0.29和p = 0.42）。在亚组分析中，TSU-68联合多西他赛与蒽环类耐药患者的总生存率相关（HR = 0.3; 95% CI = 0.1-0.8; p = 0.02）。两组中最常见的不良事件是中性粒细胞减少症和厌食症。尽管两种方案均具有良好的耐受性，但在TSU-68加多西紫杉醇组中更常观察到3/4级非血液学毒性。在蒽环类药物预处理的乳腺癌患者中，TSU-68联合多西他赛耐受性良好，但未能显示出比单独多西他赛更好的疗效。由于TSU-68在蒽环类耐药亚组中与更好的生存率相关，因此在该亚组中应进一步探索。
SummaryThe novel oral antiangiogenic agent TSU-68 was investigated in patients with metastatic breast cancer. Patients with anthracycline-pretreated metastatic breast cancer were randomly assigned to receive either TSU-68 400 mg twice daily on days 1–21 plus docetaxel 60 mg/m2 on day 1 every 3 weeks, or docetaxel 60 mg/m2 on day 1 every 3 weeks. The primary endpoint was progression-free survival. Between November 2006 and December 2007, 81 patients were included in this study (41 for TSU-68 plus docetaxel and 40 for docetaxel alone). Median progression-free survival was 6.8 months (95 % confidence interval [CI] = 5.4–12.5 months) in the TSU-68 plus docetaxel group and 8.1 months (95 % CI = 4.0–13.7 months) in the docetaxel-alone group (hazard ratio [HR] = 1.0; 95 % CI = 0.6–1.8; p = 0.95). There were no significant differences in the overall response rates and overall survival between groups (p = 0.29 and p = 0.42, respectively). In subgroup analysis, TSU-68 plus docetaxel was associated with better overall survival than docetaxel alone in anthracycline-resistant patients (HR = 0.3; 95 % CI = 0.1–0.8; p = 0.02). The most frequent adverse events were neutropenia and anorexia in both arms. Although both regimens were well tolerated, grade 3/4 non-hematologic toxicity was more frequently observed in the TSU-68 plus docetaxel group. Combination of TSU-68 and docetaxel is well tolerated but failed to demonstrate superior efficacy over docetaxel alone in anthracycline-pretreated breast cancer patients. As TSU-68 was associated with better survival in the anthracycline-resistant subgroup, it should be further explored in this subgroup.