Clinical Efficacy of Including Capecitabine in Neoadjuvant Chemotherapy for Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundCapecitabine has proven effective as a chemotherapy for metastatic breast cancer. Though several Phase II/III studies of capecitabine as neoadjuvant chemotherapy have been conducted, the results still remain inconsistent. Therefore, we performed a meta-analysis to obtain more precise understanding of the role of capecitabine in neoadjuvant chemotherapy for breast cancer patients. MethodsThe electronic database PubMed and online abstracts from ASCO and SABCS were searched to identify randomized clinical trials comparing neoadjuvant chemotherapy with or without capecitabine in early/operable breast cancer patients without distant metastasis. Risk ratios were used to estimate the association between capecitabine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool data in RevMan 5.1. ResultsFive studies were included in the meta-analysis. Neoadjuvant use of capecitabine with anthracycline and/or taxane based therapy was not associated with significant improvement in clinical outcomes including: pathologic complete response in breast (pCR; RR = 1.10, 95% CI 0.87–1.40, p = 0.43), pCR in breast tumor and nodes (tnpCR RR = 0.99, 95% CI 0.83–1.18, p = 0.90), overall response rate (ORR; RR = 1.00, 95% CI 0.94–1.07, p = 0.93), or breast-conserving surgery (BCS; RR = 0.98, 95% CI 0.93–1.04, p = 0.49). ConclusionsNeoadjuvant treatment of breast cancer involving capecitabine did not significantly improve pCR, tnpCR, BCS or ORR. Thus adding capecitabine to neoadjuvant chemotherapy regimes is unlikely to improve outcomes in breast cancer patients without distant metastasis. Further research is required to establish the condition that capecitabine may be useful in breast cancer neoadjuvant chemotherapy.背景 卡培他滨（capecitabine）已被证实对转移性乳腺癌具有良好的化疗效果。尽管已有多项针对卡培他滨作为新辅助化疗方案的Ⅱ/Ⅲ期临床研究开展，但相关研究结果仍存在不一致性。因此，本研究开展一项荟萃分析，以期更精准地阐明卡培他滨在无远处转移的乳腺癌患者新辅助化疗中的作用。方法 检索电子数据库PubMed以及美国临床肿瘤学会（ASCO, American Society of Clinical Oncology）、圣安东尼奥乳腺癌研讨会（SABCS, San Antonio Breast Cancer Symposium）的在线摘要，筛选对比早期/可手术且无远处转移的乳腺癌患者应用含卡培他滨与不含卡培他滨的新辅助化疗方案的随机对照临床试验。采用风险比（risk ratio, RR）评估新辅助化疗中加入卡培他滨与各项疗效结局之间的关联。使用RevMan 5.1软件，采用固定效应模型或随机效应模型合并研究数据。结果 本荟萃分析共纳入5项研究。在基于蒽环类和/或紫杉类的治疗方案中加入卡培他滨作为新辅助治疗，并未显著改善多项临床结局：包括乳腺病理完全缓解（pathologic complete response, pCR；RR=1.10，95%CI 0.87~1.40，p=0.43）、乳腺及腋窝淋巴结病理完全缓解（tnpCR；RR=0.99，95%CI 0.83~1.18，p=0.90）、总体缓解率（overall response rate, ORR；RR=1.00，95%CI 0.94~1.07，p=0.93）以及保乳手术率（breast-conserving surgery, BCS；RR=0.98，95%CI 0.93~1.04，p=0.49）。结论 针对无远处转移的乳腺癌患者，在新辅助化疗方案中加入卡培他滨，并未显著改善pCR、tnpCR、BCS或ORR。因此，在新辅助化疗方案中添加卡培他滨，不太可能改善此类患者的治疗结局。未来仍需开展进一步研究，以明确卡培他滨在乳腺癌新辅助化疗中的适用场景。