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在乳腺癌一线化疗中添加卡培他滨可提高乳腺癌患者的生存率。

Addition of Capecitabine in Breast Cancer First-line Chemotherapy Improves Survival of Breast Cancer Patients.

作者信息

Xu Di, Chen Xiu, Li Xingjiang, Mao Zhixiang, Tang Wenjuan, Zhang Wei, Ding Li, Tang Jinhai

机构信息

Department of General Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People's Republic of China.

Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, People's Republic of China.

出版信息

J Cancer. 2019 Jan 1;10(2):418-429. doi: 10.7150/jca.29739. eCollection 2019.

DOI:10.7150/jca.29739
PMID:30719136
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6360291/
Abstract

Capecitabine is an antimetabolic fluoropyrimidine deoxynucleoside carbamate drug that can be converted to 5-FU . Currently, the role of capecitabine in the treatment of advanced breast cancer has been recognized. Also, Several meta-analyses have elucidated the role of capecitabine in the treatment of breast cancer, indicating that taxane-based regimen with capecitabine may be an effective, convenient, and well tolerated regimen in patients with early breast cancer. However, the correlation between capecitabine-based combination first-line chemotherapy and breast cancer survival remains unclear. Here, we present a meta-analysis to systematically evaluate the safety and effectiveness of capecitabine-based combination with first-line chemotherapy treatment in breast cancer. We searched Pubmed, Embase, and Medline for relevant studies evaluating pooled estimated hazard ratios of capecitabine in breast cancer patients with the eligible criteria up to June 2018. Fixed and random-effect meta-analyses were conducted based on heterogeneity of included studies. Overall, 10 articles with 12,872 patients were included in the meta-analysis. Capecitabine-based combination first-line chemotherapy compared with non-combination had significant impacts on disease-free survival (HR = 0.84, 95% CI: 0.76-0.93; P = 0.000) and overall survival (HR = 0.84, 95% CI: 0.74-0.94; P = 0.001). Also, according to the 3 articles concerning neoadjuvant chemotherapy which included 2534 participants, we found that the addition of capecitabine significantly improved OS (HR = 0.89, 95% CI: 0.63-0.86; P = 0.011). In the subgroup analysis, TNBC patients got significant benefits with the addition of capecitabine in DFS (HR = 0.77, 95% CI: 0.65-0.92; P = 0.004) and OS (HR = 0.65, 95% CI: 0.51-0.81; P = 0.000). ER negative patients got significant benefits in OS (HR = 0.73, 95% CI: 0.57-0.93; P = 0.012). The association of DFS with the addition of capecitabine in Her- patients (HR = 0.84, 95% CI: 0.71-0.99; P = 0.005) was significant, as was OS (HR = 0.82, 95% CI: 0.70-0.95; P = 0.009),. Meanwhile, patients receiving capecitabine-based combination first-line chemotherapy underwent less adverse effects especially the grade 3/4 leucopenia than patients with non-combination therapy (RR=0.72 95% CI: 0.59-0.86; P = 0.000). Capecitabine combined with first-line chemotherapy in the treatment of breast cancer is an effective and safe treatment option and is worthy of clinical application to improve survival of breast cancer patients. In the future, we can continue to carry out relevant researches to explore the upmost appropriate dose of capecitabine for breast cancer.

摘要

卡培他滨是一种抗代谢的氟嘧啶脱氧核苷氨基甲酸酯类药物,可转化为5-氟尿嘧啶(5-FU)。目前,卡培他滨在晚期乳腺癌治疗中的作用已得到认可。此外,多项荟萃分析阐明了卡培他滨在乳腺癌治疗中的作用,表明含卡培他滨的紫杉烷类方案可能是早期乳腺癌患者有效、方便且耐受性良好的治疗方案。然而,基于卡培他滨的一线联合化疗与乳腺癌生存率之间的相关性仍不明确。在此,我们进行一项荟萃分析,以系统评估基于卡培他滨的一线联合化疗在乳腺癌治疗中的安全性和有效性。我们检索了PubMed、Embase和Medline,查找截至2018年6月符合纳入标准的评估卡培他滨在乳腺癌患者中合并估计风险比的相关研究。根据纳入研究的异质性进行固定效应和随机效应荟萃分析。总体而言,10篇文章共纳入12872例患者进行荟萃分析。与非联合化疗相比,基于卡培他滨的一线联合化疗对无病生存期(HR = 0.84,95%CI:0.76 - 0.93;P = 0.000)和总生存期(HR = 0.84,95%CI:0.74 - 0.94;P = 0.001)有显著影响。此外,根据3篇涉及新辅助化疗的文章(共纳入2534名参与者),我们发现添加卡培他滨可显著改善总生存期(HR = 0.89,95%CI:0.63 - 0.86;P = 0.011)。在亚组分析中,三阴性乳腺癌(TNBC)患者在添加卡培他滨后,无病生存期(HR = 0.77,95%CI:0.65 - 0.92;P = 0.004)和总生存期(HR = 0.65,95%CI:0.51 - 0.81;P = 0.000)均有显著获益。雌激素受体(ER)阴性患者在总生存期方面有显著获益(HR = 0.73,95%CI:0.57 - 0.93;P = 0.012)。在人表皮生长因子受体(Her-)阴性患者中,添加卡培他滨与无病生存期(HR = 0.84,95%CI:0.71 - 0.99;P = 0.005)和总生存期(HR = 0.82,95%CI:0.70 - 0.95;P = 0.009)的相关性均显著。同时,接受基于卡培他滨的一线联合化疗的患者比接受非联合化疗的患者不良反应更少,尤其是3/4级白细胞减少(RR = 0.低剂量卡培他滨联合一线化疗在乳腺癌治疗中是一种有效且安全的治疗选择,值得临床应用以提高乳腺癌患者的生存率。未来,我们可以继续开展相关研究,探索卡培他滨用于乳腺癌治疗的最适宜剂量。 72,95%CI:0.59 - 0.86;P = 0.000)。卡培他滨联合一线化疗在乳腺癌治疗中是一种有效且安全的治疗选择,值得临床应用以提高乳腺癌患者的生存率。未来,我们可以继续开展相关研究,探索卡培他滨用于乳腺癌治疗的最适宜剂量。

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J Clin Oncol. 2013 Oct 10;31(29):3623-30. doi: 10.1200/JCO.2012.45.0940. Epub 2013 Sep 3.
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German adjuvant intergroup node-positive study: a phase III trial to compare oral ibandronate versus observation in patients with high-risk early breast cancer.德国辅助性国际协作组淋巴结阳性研究:一项比较高危早期乳腺癌患者口服伊班膦酸盐与观察组的 III 期临床试验。
J Clin Oncol. 2013 Oct 1;31(28):3531-9. doi: 10.1200/JCO.2012.47.2167. Epub 2013 Aug 26.
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Clinical efficacy of including capecitabine in neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis of randomized controlled trials.含卡培他滨的新辅助化疗治疗乳腺癌的临床疗效:系统评价和随机对照试验的荟萃分析。
PLoS One. 2013;8(1):e53403. doi: 10.1371/journal.pone.0053403. Epub 2013 Jan 3.