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

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

Abstract

Objective: Capecitabine is an antimetabolic fluoropyrimidine deoxynucleoside carbamate drug that can be converted to 5-FU in vivo. 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. Methods: 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. Results: 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). Conclusion: 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.

Keywords: breast cancer; capecitabine; disease-free survival (DFS); overall survival (OS).