转移性乳腺癌蒽环类密集化疗比较

　　化疗剂量和给药强度对转移性乳腺癌的影响仍然存在争议。

　　2019年4月26日，施普林格·自然《乳腺癌研究与治疗》在线发表澳大利亚新西兰乳腺癌研究协作组、纽卡斯尔耶稣圣母医院、悉尼大学、皇家墨尔本医院、查尔斯盖德纳爵士医院、皇家北岸医院、纽卡斯尔大学的ANZ9311研究最终结果报告，对转移性乳腺癌表柔比星＋环磷酰胺化疗方案总剂量相同的大剂量短疗程与小剂量长疗程进行了比较。

　　该非盲随机对照临床研究于1994年4月～1998年7月入组转移性乳腺癌女性235例，按1∶1随机分组：

• 密集给药118例：表柔比星150mg/m²＋环磷酰胺1500mg/m²＋粒细胞集落刺激因子，每3周1次×3次，共9周

• 标准给药117例：表柔比星75mg/m²＋环磷酰胺750mg/m²，每3周1次×6次，共18周

　　主要结局为疾病进展时间、总生存、生活质量。

　　结果，密集给药与标准给药相比：

• 按计划给药率：90%比96%

• 疾病进展时间：5.7比5.8个月（P=0.19）

• 总生存时间：14.5比16.5个月（P=0.29）

• 肿瘤客观缓解：33比42例（28%比36%）

• 生活质量评分：治疗期间较低、治疗期后相似

• 血液毒性反应：发生比例较高

　　因此，该研究结果表明，对于转移性乳腺癌患者，表柔比星＋环磷酰胺化疗方案总剂量相同的大剂量短疗程与小剂量长疗程相比，疾病进展、总生存或生活质量并无改善。

相关阅读

• 定制剂量密集化疗不改善高风险早期乳腺癌女性无复发生存

• 减法时代：早期乳腺癌化疗的加法

• 中国学者发现术前或术后紫杉醇治疗时机并不影响乳腺癌患者的生存

• 早期乳腺癌患者的最佳辅助化疗方案：不应移除表柔比星＋环磷酰胺→紫杉醇

• 难治型乳腺癌的新辅助化疗：常规或密集？同步或序贯？

• 蒽环类药物治疗乳腺癌中国专家共识

• 荷兰斗牛士：早期乳腺癌术后两大辅助化疗方案头对头随机对照研究

• 乳腺癌肥胖患者辅助化疗剂量优化

Breast Cancer Res Treat. 2019 Apr 26.

Dose intensity in anthracycline-based chemotherapy for metastatic breast cancer: mature results of the randomised clinical trial ANZ 9311.

Stephen. P. Ackland, V. Gebski, N. Zdenkowski, A. Wilson, M. Green, S. Tees, H. Dhillon, G. Van Hazel, J. Levi, R. J. Simes, J. F. Forbes, A. S. Coates; Breast Cancer Trials Ltd; Australia and New Zealand Breast Cancer Trials Group.

Calvary Mater Newcastle Hospital, Newcastle, Australia; University of Sydney, Sydney, Australia; Royal Melbourne Hospital, Parkville, Australia; Breast Cancer Trials Ltd., Newcastle, Australia; Sir Charles Gairdner Hospital, Nedlands, Australia; Royal North Shore Hospital, St Leonards, Australia; University of Newcastle, Newcastle, Australia.

PURPOSE: The separate impacts of dose and dose intensity of chemotherapy for metastatic breast cancer remain uncertain. The primary objective of this trial was to compare a short, high-dose, intensive course of epirubicin and cyclophosphamide (EC) with a longer conventional dose regimen delivering the same total dose of chemotherapy.

METHODS: This open label trial randomised 235 women with metastatic breast cancer to receive either high-dose epirubicin 150 mg/m² and cyclophosphamide 1500 mg/m² with filgrastim support every 3 weeks for 3 cycles (HDEC) or standard dose epirubicin 75 mg/m² and cyclophosphamide 750 mg/m² every 3 weeks for 6 cycles (SDEC). Primary outcomes were time to progression, overall survival and quality of life.

RESULTS: In 118 patients allocated HDEC 90% of the planned dose was delivered, compared to 96% in the 117 participants allocated SDEC. There were no significant differences in the time to disease progression (5.7 vs. 5.8 months, P=0.19) or overall survival (14.5 vs. 16.5 months, P=0.29) between HDEC and SDEC, respectively. Patients on HDEC reported worse quality of life during therapy, but scores improved after completion to approximate those reported by patients allocated SDEC. Objective tumour response was recorded in 33 (28%) on HDEC and 42 patients (36%) on SDEC. HDEC produced more haematologic toxicity.

CONCLUSION: For women with metastatic breast cancer, disease progression, survival or quality of life were no better with high-dose intensity compared to standard dose EC chemotherapy.

Australian Clinical Trials Registry registration number: ACTRN12605000478617

KEYWORDS: Breast cancer Chemotherapy Anthracycline Dose intensity Survival Quality of life

DOI: 10.1007/s10549-019-05187-y