Tortoriello A, Facchini G, Caponigro F, Santangelo M, Benassai G, Persico G, Citarella A, Carola M, Marzano N, Iaffaioli R V
Istituto di Medicina Interna, Università di Cagliari, Italy.
Breast Cancer Res Treat. 1998 Jan;47(1):91-7. doi: 10.1023/a:1005848921895.
Paclitaxel and vinorelbine are among the most active new agents in metastatic breast cancer. Both in vitro and in vivo studies have shown that the combined administration of these two microtubule-targeting agents is feasible and worthwhile. Based on the promising preclinical data, patients with metastatic breast cancer no longer amenable to conventional treatment were entered into a phase I/II study in which the vinorelbine dose was fixed at 30 mg/sqm and paclitaxel was started at 90 mg/sqm and then subsequently escalated by 30 mg/sqm per step. Cycles were repeated every 21 days. Hematopoietic growth factor support was provided from the 4th dose level onwards. Grade III neutropenia was observed only in 2 patients treated at the 5th dose level. Thrombocytopenia never reached grade 3. Neurotoxicity was considered dose-limiting, since grade 3 peripheral neuropathy occurred in all three patients treated at the 6th dose level. Other toxicities were mild. Paclitaxel 210 mg/sqm and vinorelbine 30 mg/sqm was the selected combination for phase II. Overall response rate in 34 evaluable patients was 38% (95% confidence interval (C.I.), 22% to 54%). In particular, 3 complete responses (9%) and 10 partial responses (29%) were observed. The observed level of antitumor activity, with an overall response rate of 38% and a median duration of response of 12 months, is of interest, since the study was targeted only to anthracycline-pretreated patients, most of whom had adverse prognostic features. The evaluation of a combination of vinorelbine and paclitaxel as first-line therapy in metastatic breast cancer seems worthwhile and is currently undergoing.
紫杉醇和长春瑞滨是转移性乳腺癌中最有效的新型药物之一。体外和体内研究均表明，联合使用这两种微管靶向药物是可行且值得的。基于有前景的临床前数据，将不再适合传统治疗的转移性乳腺癌患者纳入一项I/II期研究，其中长春瑞滨剂量固定为30mg/m²，紫杉醇起始剂量为90mg/m²，随后每步递增30mg/m²。每21天重复一个周期。从第4剂量水平开始提供造血生长因子支持。仅在第5剂量水平治疗的2例患者中观察到III级中性粒细胞减少。血小板减少从未达到3级。神经毒性被认为是剂量限制性的，因为在第6剂量水平治疗的所有3例患者中均出现了3级周围神经病变。其他毒性较轻。紫杉醇210mg/m²和长春瑞滨30mg/m²是II期研究选择的联合方案。34例可评估患者的总缓解率为38%（95%置信区间（C.I.），22%至54%）。特别是，观察到3例完全缓解（9%）和10例部分缓解（29%）。观察到的抗肿瘤活性水平，总缓解率为38%，中位缓解持续时间为12个月，是值得关注的，因为该研究仅针对接受过蒽环类药物预处理的患者，其中大多数具有不良预后特征。评估长春瑞滨和紫杉醇联合作为转移性乳腺癌的一线治疗似乎是值得的，目前正在进行中。
