摘要目的 重组人血管内皮抑制素( rh-Endostatin)是我国自主研发的新型血管生成抑制剂.观察rh-Endostatin联合新辅助多西他赛和表阿霉素(DE)方案治疗乳腺癌的前瞻、随机、对照性Ⅱ期临床试验,以评价rh-Endostatin联合化疗治疗乳腺癌的疗效和安全性.方法 将2008年2月至2010年3月第四军医大学西京医院收治的68例经组织学穿刺确诊的ⅡA-ⅢC期乳腺癌患者随机分为两组,分别给予标准DE三周方案(多西他赛,75 mg/m2,d1；表阿霉素75 mg/m2,d1)化疗或DE联合rh-Endostatin,7.5 mg/m2,d1 ～ d14,21 d为1周期,治疗3个周期后手术.主要研究终点为肿瘤客观缓解率(ORR)和病理完全缓解率(PCRR),次要研究终点为患者生存质量(QOL)和不良反应.结果 64例可评价疗效的患者中,试验组和对照组的ORR分别为90.9％( 30/33)和67.7％(21/31),差异有统计学意义(P=0.021).分层分析发现,rh-Endostatin对于绝经前及ECOG评分为0的病例疗效更显著,差异有统计学意义(P＜0.05).试验组和对照组的PCRR分别为15.2％( 5/33)和6.5％(2/31),差异无统计学意义(P =0.428).两组患者治疗前后的QOL评分与不良反应发生率差异亦无统计学意义(P＞0.05).结论 rh-Endostatin联合新辅助DE化疗在乳腺癌临床试验中显示出更好的疗效,ORR明显增高,未增加不良反应,是一种安全有效的治疗方案.

abstractsObjective Recombinant human endostatin (rh-Endostatin),a protein modified by an additional nine-amino acid sequence to the N-terminal of endostatin,is a novel antiangiogenesis drug developed in China.The preclinical data suggested that it can inhibit proliferation and migration not only in endothelial cells,but also in some types of tumor cells.Theoretically,antiangiogenesis drugs should also be effective in the therapy of other solid tumors,including breast cancer. Here a prospective,randomized,controlled,phase Ⅱ trial of combining rh-Endostatin and neoadjuvant chemotherapy was performed to evaluate its efficacy and safety profiles in patients with breast cancer.Methods A total of 68 patients with pathologically confirmed breast cancer were randomly assigned to receive the neoadjuvant DE regimen (docetaxel:75 mg/m2,d1,epirubicin:75 mg/m2,d1 ) every 3 weeks with or without rh-Endostatin (7.5 mg/m2,d1 -d14).Surgical resection was performed after 3 cycles of neoadjuvant treatment.The primary end-points were objective response rate (ORR) and pathological complete response rate (PCRR) while the secondary end-points quality of life (QOL) and toxicity.Results Among all of them,64 were assessable for efficacy and 68 for toxicity.The ORRs were 90.9％ (30/33) and 67.7％ (21/31) in the combination and control groups respectively ( P =0.021 ).The stratification analysis showed that rh-Endostatin was more effective in the treatment of pre-menopausal and Eastern Cooperative Oncology Group (ECOG) =0 patients (P＜0.05).The PCRRs were 15.2％ (5/33) and 6.5％ (2/31) in the combination and control groups respectively (P =0.428 ).No significant difference was identified in QOL score and side effects ( P ＞ 0.05).Conclusions Compared with DE regimen alone,the combination of th-Endostatin with DE chemotherapy may achieve a higher ORR with no increased toxicity in breast cancer patients.Thus it can be utilized safely and effectively in the neoadjuvant treatment of breast cancer.