Sandro Pitigliani Medical Oncology Unit, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy.
Ann Oncol. 2013 May;24(5):1203-11. doi: 10.1093/annonc/mds627. Epub 2013 Jan 4.
Background In women with node-positive breast cancer, the Breast International Group (BIG) 02-98 tested the incorporation of docetaxel (Taxotere) into doxorubicin (Adriamycin)-based chemotherapy, and compared sequential and concurrent docetaxel. At 5 years, there was a trend for improved disease-free survival (DFS) with docetaxel. We present results at 8-year median follow-up and exploratory analyses within biologically defined subtypes. Methods Patients were randomly assigned to one of four treatments: (i) sequential control: doxorubicin (A) (75 mg/m(2)) × 4 →classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF); (ii) concurrent control: doxorubicin, cyclophosphamide (AC)(60/600 mg/m(2)) × 4 →CMF; (iii) sequential docetaxel: A (75 mg/m(2)) × 3 → docetaxel (T) (100 mg/m(2)) × 3 → CMF and (iv) concurrent docetaxel: AT(50/75 mg/m(2)) × 4 →CMF. The primary comparison evaluated docetaxel efficacy regardless of the schedule. Exploratory analyses were undertaken within biologically defined subtypes. Results Two thousand eight hundred and eighty-seven patients were enrolled. After 93.4 months of median follow-up, there were 916 DFS events. For the primary comparison, there was no significant improvement in DFS from docetaxel [hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.80-1.05, P = 0.187]. In secondary comparisons, sequential docetaxel significantly improved DFS compared with sequential control (HR = 0.81, 95% CI = 0.67-0.99, P = 0.036), and significantly improved DFS (HR = 0.84, 95% CI = 0.72-0.99, P = 0.035) and overall survival (OS) (HR = 0.79, 95% CI = 0.65-0.98, P = 0.028) compared with concurrent doxorubicin-docetaxel. Luminal-A disease had the best prognosis. HRs favored addition of sequential docetaxel in all subtypes, except luminal-A; but this observation was not statistically supported because of limited numbers. Conclusion With further follow-up, the sequential docetaxel schedule resulted in significantly better OS than concurrent doxorubicin-docetaxel, and continued to show better DFS than sequential doxorubicin-based control.
背景 在淋巴结阳性乳腺癌女性中，BIG 02-98 试验检测了多西紫杉醇（泰索帝）联合蒽环类药物（阿霉素）化疗的效果，并比较了序贯和同时使用多西紫杉醇。5 年时，多西紫杉醇治疗有改善无病生存（DFS）的趋势。我们在 8 年中位随访时报告了结果，并对生物学定义的亚组进行了探索性分析。
方法 患者被随机分配到以下 4 种治疗方案之一：（i）序贯对照组：阿霉素（A）（75mg/m2）×4→经典环磷酰胺、甲氨蝶呤、5-氟尿嘧啶（CMF）；（ii）同时对照组：阿霉素、环磷酰胺（AC）（60/600mg/m2）×4→CMF；（iii）序贯多西紫杉醇组：A（75mg/m2）×3→多西紫杉醇（T）（100mg/m2）×3→CMF；（iv）同时多西紫杉醇组：AT（50/75mg/m2）×4→CMF。主要比较评估了多西紫杉醇的疗效，而不考虑方案。对生物学定义的亚组进行了探索性分析。
结果 共纳入 2887 例患者。中位随访 93.4 个月后，有 916 例 DFS 事件。对于主要比较，多西紫杉醇并未显著改善 DFS[风险比（HR）=0.91，95%置信区间（CI）=0.80-1.05，P=0.187]。在次要比较中，与序贯对照组相比，序贯多西紫杉醇显著改善 DFS（HR=0.81，95%CI=0.67-0.99，P=0.036），并且显著改善 DFS（HR=0.84，95%CI=0.72-0.99，P=0.035）和总生存（OS）（HR=0.79，95%CI=0.65-0.98，P=0.028）。 luminal-A 疾病的预后最好。在所有亚组中，除了 luminal-A 亚组外，添加序贯多西紫杉醇的 HR 均有利，但由于例数有限，这一观察结果未得到统计学支持。
结论 在进一步随访中，序贯多西紫杉醇方案与同时使用多西紫杉醇-阿霉素相比，OS 显著改善，与序贯蒽环类药物为基础的对照组相比，DFS 持续改善。
