紫杉烷类药物:优化早期乳腺癌辅助化疗。

Taxanes: optimizing adjuvant chemotherapy for early-stage breast cancer.

机构信息

Department of Medical Oncology, Jules Bordet Institute, Rue Heger-Bordet 1, Brussels, Belgium.

出版信息

Nat Rev Clin Oncol. 2010 Jan;7(1):22-36. doi: 10.1038/nrclinonc.2009.186. Epub 2009 Dec 8.

Abstract

Taxanes are among the most widely used chemotherapy agents for advanced breast cancer. Results are now available from 21 trials that randomly allocated nearly 36,000 women with early-stage breast cancer to receive first-generation taxane-based adjuvant chemotherapy versus non-taxane-based adjuvant regimens. Three recent meta-analyses suggest that taxanes are beneficial in the adjuvant setting, irrespective of the patient's age, lymph-node involvement, hormone-receptor expression, and HER2 status. Nevertheless, the optimal role for taxanes in the adjuvant management of early-stage breast cancer remains controversial. We review the results of the first-generation taxane trials and discuss possible explanations for the differences observed in these studies, including variation in the 'strength' of anthracycline therapy in the control arms; suboptimal timing, dosing, or schedule of the taxane regimen; a masking effect of trials that included patients with relatively chemotherapy-insensitive luminal A disease; and decreased representation of the putative taxane-sensitive disease subset. Inclusion criteria for future clinical trials must be revised to account for the molecular heterogeneity of breast cancer and further optimize the role of adjuvant taxane therapy in early-stage disease.

摘要

紫杉烷类药物是晚期乳腺癌最广泛使用的化疗药物之一。目前已有 21 项试验的结果可供参考,这些试验将近 36000 名早期乳腺癌患者随机分配接受第一代紫杉烷类辅助化疗与非紫杉烷类辅助方案。最近的三项荟萃分析表明,紫杉烷类药物在辅助治疗中有获益,无论患者的年龄、淋巴结受累情况、激素受体表达和 HER2 状态如何。然而,紫杉烷类药物在早期乳腺癌辅助治疗中的最佳作用仍存在争议。我们回顾了第一代紫杉烷类药物试验的结果,并讨论了这些研究中观察到的差异的可能解释,包括对照臂中蒽环类药物治疗的“强度”变化;紫杉烷方案的时机、剂量或方案选择不当;包含相对化疗敏感性 luminal A 疾病患者的试验的掩盖效应;以及推测的紫杉烷敏感疾病亚组的代表性降低。未来临床试验的纳入标准必须进行修订,以考虑乳腺癌的分子异质性,并进一步优化辅助紫杉烷治疗在早期疾病中的作用。

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