Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37298 women with early breast cancer in 26 randomised trials
Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37298 women with early breast cancer in 26 randomised trials
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DOI：
10.1016/s0140-6736(18)33137-4
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发表时间：
2019-04-06
期刊：
影响因子：
168.9
通讯作者：
Zambetti, M.
中科院分区：
文献类型：
--
作者：
Boddington, C.;Bradley, R.;Zambetti, M.
背景：通过缩短周期之间的间隔，或通过以全剂量序贯给予个体药物而不是以低剂量并行治疗方案来增加细胞毒性治疗的剂量强度，可能会提高疗效.方法：为了阐明早期乳腺癌剂量密集和标准方案化疗的相对获益和风险，我们进行了一项个体患者水平的荟萃分析，比较了2周一次与标准3周一次方案的试验，以及比较蒽环类药物和紫杉烷化疗序贯与同时给药的试验。主要结局是复发和乳腺癌死亡率。标准的意向治疗对数秩分析，分层的年龄，淋巴结的状态，和试验，产生剂量密集与标准的时间表首次事件率ratios（RRs）。结果提供了26个33个相关的试验确定，包括37 298（93%）的40 070名妇女随机。大多数妇女年龄小于70岁，患有淋巴结阳性疾病。两个治疗组的总细胞毒性药物使用量大致相当;集落刺激因子通常用于剂量密集组。综合所有26项试验的数据，与标准方案化疗相比，剂量密集组乳腺癌复发率更低（10年复发风险28.0% vs 31.4%; RR 0.86，95%CI 0.82-0.89; p < 0.05）。
Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy.Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs).Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28.0% vs 31.4%; RR 0.86, 95% CI 0.82-0.89; p