Mouridsen H T
Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
Clin Breast Cancer. 2000 Sep;1 Suppl 1:S34-40. doi: 10.3816/cbc.2000.s.007.
The taxanes paclitaxel and docetaxel have an important role in the treatment of breast cancer, and numerous randomized trials have evaluated their efficacy for this indication. A systematic, evidence-based review was performed, which included all randomized, controlled trials evaluating taxanes for the treatment of early- or advanced-stage breast cancer that were identified in CANCERLIT and MEDLINE searches. The primary objectives of this review were to determine the dose and schedule for each taxane that was associated with the most favorable therapeutic index, and to determine whether (and under what circumstances) the taxanes improved survival. The search revealed 18 randomized phase II (n=1) or phase III (n=17) trials. For metastatic breast cancer, the dose and schedule associated with the most favorable therapeutic index for paclitaxel was 175 mg/m2 given as a 3-hour infusion every 3 weeks, and docetaxel was 60-100 mg/m2 given as a 1-hour infusion every 3 weeks. Survival was improved under the following circumstances: (1) when 4 cycles of paclitaxel (175 mg/m2 every 3 weeks) was given following 4 cycles of conventional doxorubicin- cyclophosphamide for axillary node-positive operable breast cancer, (2) when trastuzumab was added to paclitaxel as first-line therapy for metastatic breast cancer that overexpressed HER2/neu, and (3) when docetaxel was given as second-line therapy for anthracycline-resistant disease. Although a survival benefit was found for taxanes as a component of first-line therapy in two of six trials, the interpretation of both positive trials was confounded by a lack of crossover to taxane therapy in those who were initially randomized to receive standard therapy. The taxanes improve survival in patients with early-stage breast cancer and selected patients with metastatic breast cancer. Further research is necessary in order to identify the efficacy of docetaxel relative to paclitaxel, the optimal dose of docetaxel, the role of weekly taxane therapy, the role of trastuzumab plus taxanes in early-stage disease, and whether taxanes are more effective when given concomitantly or sequentially in patients with early-stage disease
紫杉烷类药物紫杉醇和多西他赛在乳腺癌治疗中具有重要作用，众多随机试验评估了它们在该适应症上的疗效。我们进行了一项系统的、基于证据的综述，纳入了在CANCERLIT和MEDLINE检索中识别出的所有评估紫杉烷类药物治疗早期或晚期乳腺癌的随机对照试验。本综述的主要目的是确定每种紫杉烷类药物与最有利治疗指数相关的剂量和给药方案，并确定紫杉烷类药物是否（以及在何种情况下）能改善生存率。检索发现了18项随机II期（n = 1）或III期（n = 17）试验。对于转移性乳腺癌，与紫杉醇最有利治疗指数相关的剂量和给药方案是每3周静脉输注3小时，剂量为175mg/m²；多西他赛是每3周静脉输注1小时，剂量为60 - 100mg/m²。在以下情况下生存率得到改善：（1）对于腋窝淋巴结阳性的可手术乳腺癌，在4周期传统阿霉素 - 环磷酰胺治疗后给予4周期紫杉醇（每3周175mg/m²）；（2）对于HER2/neu过表达的转移性乳腺癌，将曲妥珠单抗添加到紫杉醇中作为一线治疗；（3）对于蒽环类耐药疾病，将多西他赛作为二线治疗。尽管在六项试验中的两项中发现紫杉烷类药物作为一线治疗的一部分有生存获益，但这两项阳性试验的解读因最初随机接受标准治疗的患者缺乏交叉接受紫杉烷类药物治疗而受到混淆。紫杉烷类药物可提高早期乳腺癌患者和部分转移性乳腺癌患者的生存率。有必要进一步研究以确定多西他赛相对于紫杉醇的疗效、多西他赛的最佳剂量、每周紫杉烷类药物治疗的作用、曲妥珠单抗加紫杉烷类药物在早期疾病中的作用，以及紫杉烷类药物在早期疾病患者中联合或序贯给药时是否更有效。
