| Objective: This study compared the efficiency and toxicity between S-1 and X in treating anthracycline or paclitaxel refractory advanced breast cancer(ABC). And it analysed efficacy,adverse events,survival analysis and the factors affecting patient’s survival. Thus it can provide better options for clinical treatment of anthracycline or paclitaxel refractory ABC.Methods:1 This research has selected 154 hospitalized patients who were diagnosed by pathology as ABC and were treated initially in 12 centers from Jan.1st, 2012 to Dec.31 st, 2014. It reviewed and analyzed their clinical data. According to the selected chemotherapy regimens,the patients were separated into two groups:S-1+/- new agents(Group A),Xeloda+/- new agents(Group B). New agents including Gemcitabine, Taxol, Docetaxel and Vinorelbine. The efficiency was evaluated according to RECIST v1.1 evaluation criteria after two or three cycles(Patients who had the local-regional progression after receiving only 1 cycle chemotherapy were contained). Objective response rate(ORR:CR+PR),disease control rate(DCR:CR+PR+SD) and progression free survival(PFS)were compared between two groups. To get to know the influence factors of survival, we analyzed the data between groups by age, with or without chronic disease(such as hypertension, diabetes mellitus, coronary artery disease and venous thromboembolism),T category,ER/PR status,HER2 status,the number of lymph node, metastatic number, with or without brain metastasis, molecular subtypes, therapy time and so on. The adverse reactions were evaluated by WHO chemotherapy adverse reaction classification standard. We compared the difference of adverse reactions among the two groups.2 We made follow-up by telephone and collecting hospitalized reexamination charts. The deadline was Dec.31 st, 2014. The starting point of this study was the time when patients participate in this study. The end point was set at the last time we made follow-up, lost to follow-up, or the time patients died. Analyzed the patients’ progression free survival(PFS) and 1 year overall survival(OS) to get to know the influence on prognosis of different drugs.3 The data were organized and processed with SPSS19.0 statistical software. Patient characteristics, the effect and adverse reactions of two groups were compared between groups using the chi-squared test or Fisher’s exact test. Kaplan-Meier method was used in survival analysis. The Log-Rank test compared the differences in survival between S-1 group and X group. Cox regression models were used to analyse factors which influenced the survival of patients. Data obtained with P values<0.05 were considered statistically significant.Results: A total of 154 cases with advanced breast cancer were eligible for inclusion in the analysis, of whom 70 received S-1(S-1 group) and 84 received Xeloda(X group).All patients had received antharcycline or paclitaxel. 8 of 154 cases losed to follow-up, follow-up rate was 94.8%.The median follow-up time was 19 months(range 1-58 months).There were no statistically significant in patients distribution except number of lymph nodes(P=0.001) and T category(P=0.032).The media chemotherapy cycle of S-1 group was 4 cycles(range 1-23 cycles),ORR was 31.4%,DCR was 74.3%.The chemotherapy cycle range of X group:1-40 cycles, median cycles:6 cycles. ORR was 28.6%,It had a DCR of 83.3%. The comparison of ORR and DCR between these two groups had no statistically significant(P values were 0.726 and 0.231).Compared the monotherapy and combined with new agents therapy between two group,the results showed DCR of X was higer than S-1,and the results had statistically significant(P=0.028),other results had no statistically significant.Subgroup analysis according to combined with different new agents,the results of analysis showed that the ORR of TS subgroup was higher than S-1 subgroup(P=0.001),there were no statistically significant between other subgroups(P>0.05).The mainly adverse events of the two groups were nausea/vomitingand myelosuppression,almost was mild-moderate.The incidence of nausea/vomiting respectively was 68.6% vs 54.8%(P=0.098) between two groups, there was no statistically significant. The rate of anemia had statistically significant between two groups(14.3% vs 36.9%,P=0.002),but the incidence of leukopenia,neutropenia,thrombocytopenia was no statistically significant. The incidence of hand-food syndrome in S-1 group was lower than X group, but there was also no statistically significant(0% vs 4.8%, P=0.126).The media PFS of S-1 group was 7.5 months(95%CI 4.4-10.6 months),X group was 8.9 months(95%CI 7.3-10.5 months).There was no statistically significant between these two groups(Log-Rank c2=0.641,P=0.423).The 1 year OS of S-1 group and X group respectively were 81.43% and 66.67%,S-1 group had better 1 year OS when compared with patients who received Xeloda(c2=5.575,P=0.020).Subgroup analysis according to number of lymph nodes,molecular subtypes,therapy time,combined with new agents showed no statistically significant. Univariate analysis showed that ER/PR status(HR=0.636,95%CI 0.466-0.868,P=0.004),T category(HR=1.211,95%CI 1.008-1.454,P=0.041),molecular subtypes(HR=1.158,95%CI 1.003-1.338,P=0.046) were the important factors in PFS. The PFS of patients who had ER/PR positive,smaller T,Luminal A was longer. The factors of chronic disease,HER-2 status,number of lymph nodes,metastatic number,metastatic site,brain metastasis,therapy time was no statistically significant in PFS. In the multivariable Cox regression model, onlyER/PR status had statistically significant in PFS(HR=0.636, 95%CI 0.466-0.868, P=0.004).Stratified analysis showed that patients with chronic disease(P=0.045), third-line therapy(P=0.047) had a better PFS in X group compared with S-1 group,and the different had statistically significant.With brain metastasis patients S-1 group had extend trend than X group,It was because of less cases,further study was needed. We did not observed effect on PFS in factors such as ER/PR status,HER-2 status,number of lymph nodes,molecular subtypes,metastatic number,metastatic site(P>0.05).Conclusion:1 Group A has higher ORR in treating patients with anthracycline or paclitaxel refractory ABC compared with Group B, but DCR is lower.2 The media PFS of group A is 7.5 months, and 8.9 months in group B, but there is no statistically significant.3 The mainly adverse events in group A are mild-moderate nausea/vomiting and myelosuppression, the incidence of almost adverse events in group A is lower than group B except nausea/vomiting. For patients with anthracycline or paclitaxel refractory ABC, the efficacy and security are no statistically significant between group A and group B, so S-1 can be used as a treatment option in clinical application.4 For the patients with ER/PR positive, smaller Tumor, Luminal A who have batter PFS. But,in multivariable Cox regression model, onlyER/PR is the independent prognostic factor for patients’ PFS. The factors of T category,molecular subtypes,chronic disease,metastatic number,brain metastasis,therapy time are no statistically significant in PFS. |
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