Department of Oncology A, Policlinico Umberto, Sapienza University of Rome, 155 V.le del Policlinico, 00161 Rome, Italy.
Ann Oncol. 2011 Feb;22(2):315-20. doi: 10.1093/annonc/mdq392. Epub 2010 Aug 6.
Through different pharmacodynamic-kinetic interactions, weekly administration of proved efficacy agents can overcome resistance with lower toxicity and greater benefit. Based on this assumption, we designed a phase I-II trial with weekly non-pegylated liposomal anthracycline and taxane in first-line breast cancer patients.
We enrolled 56 previously untreated metastatic breast cancer patients; they were randomly assigned to receive paclitaxel (Taxol) (50 mg/mq) or docetaxel (Taxotere) (30 mg/mq) combined with non-pegylated liposomal anthracycline (25 mg/mq) on days 1, 8 and 15 every 4 weeks. The primary end points were the clinical benefit and treatment-related toxic effects assessment. Secondary end points were time-to-disease progression (TTP) and overall survival (OS).
The overall clinical benefit was 87.04%. World Health Organization G3-4 toxic effects included neutropenia (45%), anemia (44%), complete alopecia (83%), severe onycholysis and neuropathy. The 24% of patients developed left ventricular ejection fraction reduction but none >10% with recover after treatment completion. The median absolute decrease from baseline was 1%. Median TTP was 11 months and median OS was 23 months.
Combined weekly administration of taxane and non-pegylated liposomal anthracycline is well tolerated and clinical benefit data encourage phase III study design.
通过不同的药效动力学相互作用，每周给药的已证明疗效的药物可以克服耐药性，毒性更低，获益更大。基于这一假设，我们设计了一项一线乳腺癌患者每周使用非聚乙二醇化脂质体阿霉素和紫杉烷的 I- II 期试验。
我们招募了 56 名未经治疗的转移性乳腺癌患者；他们被随机分配接受紫杉醇（泰素）（50mg/mq）或多西紫杉醇（泰道）（30mg/mq）联合非聚乙二醇化脂质体阿霉素（25mg/mq），于第 1、8 和 15 天，每 4 周一次。主要终点是临床获益和治疗相关毒性评估。次要终点是疾病进展时间（TTP）和总生存期（OS）。
总临床获益率为 87.04%。世界卫生组织 G3-4 级毒性包括中性粒细胞减少（45%）、贫血（44%）、完全脱发（83%）、严重甲床分离和神经病变。24%的患者发生左心室射血分数降低，但无一例>10%，并在治疗完成后恢复。中位基线绝对下降值为 1%。中位 TTP 为 11 个月，中位 OS 为 23 个月。
每周联合使用紫杉烷和非聚乙二醇化脂质体阿霉素耐受性良好，临床获益数据鼓励进行 III 期研究设计。
