口服小剂量环磷酰胺联合卡培他滨维持治疗晚期三阴性乳腺癌的疗效
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摘要
目的:观察小剂量环磷酰胺(CTX)联合卡培他滨(CAP)维持治疗晚期三阴性乳腺癌的疗效及安全性。方法:回顾性分析我院收治的经含卡培他滨方案两药联合化疗后达临床稳定的晚期三阴性乳腺癌患者68例,实验组34例给予口服环磷酰胺50 mg/d,d_(8～21),每3周重复,联合卡培他滨1 000 mg/m~2,bid,d_(1～14),休息7天。对照组34例患者仅给予口服卡培他滨单药维持治疗。观察2组患者的ORR、DCR、TTP、安全性及对生活质量的影响。结果:经维持治疗后实验组ORR为29.4%,DCR为85.3%;对照组ORR为14.7%,DCR为64.7%。实验组中位TTP为12个月,明显高于对照组中位TTP 6.9个月(P<0.05)。两组的主要不良反应为手足综合征,实验组的胃肠道反应及血液学毒性稍高于对照组,均为Ⅰ-Ⅱ度。两组患者的生活质量评分均较治疗前明显提高,治疗后组间差异无统计学意义(P>0.05)。结论:口服小剂量环磷酰胺联合卡培他滨维持治疗晚期三阴性乳腺癌有较好的疗效,不良反应可以耐受,可作为复发转移较快的晚期三阴性乳腺癌患者维持治疗的一种选择,具有一定的临床推广应用价值。
Objective:To investigate the efficacy and safety of low-dose cyclophosphamide(CTX)combined with capecitabine(CAP) maintenance therapy in patients with metastatic triple-negative breast cancer(MBC).Methods:The clinical data of 68 triple-negative MBC patients treated with capecitabine-based combination chemotherapy were retrospectively analyzed.when initial disease control was achieved by the combination chemotherapy,the experimental group 34 patients were treated with low dose of cyclophosphamide for oral 50 mg,one daily on d_(8～21) of every 3-week cycle,then capecitabine was continued for oral 1 000 mg/m~2,twice daily on d_(1～14),followed by a 7 d rest period.The control group 34 patients were treated with single-agent capecitabine maintenance therapy.We compared the time to progression(TTP),objective response rate(ORR),disease control rate(DCR),quality of life and safety of the two groups.Results:After combination chemotherapy,the ORR was 29.4%,the DCR was 85.3% in the experimental group.ORR was 14.7%,and DCR was 64.7% in the control group.The median TTP in experimental group and control group were 12 months vs 6.9 months,the difference was statistically significant(P<0.05).The major gradeⅠ/Ⅱtoxicities included hand-foot syndrome,gastrointestinal toxicities and hematologic toxicity were not significantly different between two groups.The scores of quality of life in two groups were all significantly increased after treatment,and the difference was not statistically significant between two groups(P>0.05).Conclusion:Oral low dose of cyclophosphamide combined with capecitabine maintenance therapy has clinical curative effect and favorable safety profile in treatment of metastatic triple-negative breast cancer,which provides an option for the advanced triple-negative breast cancer.It has a certain value of clinical promotion and application.
Objective:To investigate the efficacy and safety of low-dose cyclophosphamide(CTX)combined with capecitabine(CAP) maintenance therapy in patients with metastatic triple-negative breast cancer(MBC).Methods:The clinical data of 68 triple-negative MBC patients treated with capecitabine-based combination chemotherapy were retrospectively analyzed.when initial disease control was achieved by the combination chemotherapy,the experimental group 34 patients were treated with low dose of cyclophosphamide for oral 50 mg,one daily on d_(8～21) of every 3-week cycle,then capecitabine was continued for oral 1 000 mg/m~2,twice daily on d_(1～14),followed by a 7 d rest period.The control group 34 patients were treated with single-agent capecitabine maintenance therapy.We compared the time to progression(TTP),objective response rate(ORR),disease control rate(DCR),quality of life and safety of the two groups.Results:After combination chemotherapy,the ORR was 29.4%,the DCR was 85.3% in the experimental group.ORR was 14.7%,and DCR was 64.7% in the control group.The median TTP in experimental group and control group were 12 months vs 6.9 months,the difference was statistically significant(P<0.05).The major gradeⅠ/Ⅱtoxicities included hand-foot syndrome,gastrointestinal toxicities and hematologic toxicity were not significantly different between two groups.The scores of quality of life in two groups were all significantly increased after treatment,and the difference was not statistically significant between two groups(P>0.05).Conclusion:Oral low dose of cyclophosphamide combined with capecitabine maintenance therapy has clinical curative effect and favorable safety profile in treatment of metastatic triple-negative breast cancer,which provides an option for the advanced triple-negative breast cancer.It has a certain value of clinical promotion and application.
引文
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[9] Gennari A,Amadori D,De Lena M,et al.Lack of benefit of maintenance paclitaxel in first-line chemotherapy in metastatic breast cancer[J].J Clin Oncol,2006,24(24):3912-3918.
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[11] Cervantes G,Torrecillas L,Eraro AA,et al.Capecitabine (Xeloda) as treatment after failure to taxanes for metastatic breast cancer[J].Proc Am Soc Clin Oncol,2000,19:121.
[12] Wang J,Xu B,Yuan P,et al.Capecitabine combined with docetaxel versus vinorelbine followed by capecitabine maintenance medication for first-line treatment of patients with advanced breast cancer:Phase 3 randomized trial[J].Cancer,2015,121(19):3412-3421.
[13] Dong G,Jia Y,Wang X,et al.The comparison of maintenance treatment with capecitabine (CMT) and non-maintenance treatment with capecitabine (non-CMT) in patients with metastatic breast cancer[J].Int J Clin Exp Med,2015,8(5):8283-8287.
[14] Liang X,Di LJ,Song GH,et al.Capecitabine maintenance therapy for XT chemotherapy-sensitive patients with metastatic triple-negative breast cancer[J].Chin J Cancer Res,2014,26(5):550-557.
[15] Si W,Zhu YY,Li Y,et al.Capecitabine maintenance therapy in patients with recurrent or metastatic breast cancer[J].Braz J Med Biol Res,2013,46(12):1074-1081.
[16] Huang ZY,Liu FQ,Gao LC,et al.Advances in pharmacogenomics cyclophosphamide in the breast cancer therapy[J].Chin J Clin Pharmacol Ther,2014,19(10):1196-1200.[黄征宇,刘芳群,高利臣,等.乳腺癌环磷酰胺治疗的药物基因组学研究进展 [J].中国临床药理学与治疗学,2014,19(10):1196-1200.]
[17] Munzone E,Colleoni M.Clinical overview of metronomic chemotherapy in breast cancer[J].Nat Rev Clin Oncol,2015,12(11):631-644.
[18] Loeffler M,Krüger JA,Reisfeld RA.Immunostimulatory effects of low-dose cyclophosphamide are controlled by inducible nitric oxide synthase[J].Cancer Res,2005,65(12):5027-5030.
[19] Martin-Padura I,Marighetti P,Agliano A,et al.Residual dormant cancer stem-cell foci are responsible for tumor relapse after antiangiogenic metronomic therapy in hepatocellular carcinoma xenografts[J].Lab Invest,2012,92(7):952-966.
[20] Colleoni M,Rocca A,Sandri MT,et al.Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer:antitumor activity and correlation with vascular endothelial growth factor levels[J].Ann Oncol,2002,13(1):73-80.
[21] Qian Y,Ji HM,Zhang Y,et al.Clinical observation of cyclophosphamide metronomic chemotherapy plus celecoxib for advanced breast cancer[J].Journal of Basic and Clinical Oncology,2014,27(4):302-303.[钱烨,吉浩明,张燕,等.环磷酰胺节拍化疗联合塞来昔布治疗晚期乳腺癌临床观察[J].肿瘤基础与临床,2014,27(4):302-303.]
[2] Suba Z.Triple-negative breast cancer risk in women is defined by the defect of estrogen signaling:Preventive and therapeutic implications[J].Oncol Targets Ther,2014,7:147-164.
[3] Luo DF,Hong CX.Efficacy of Gemcitabine adjuvant therapy for anthracycline resistant advanced breast cancer[J].Practical J Cancer,2017,32(8):1358-1363.[罗丹凤,洪朝欣.吉西他滨辅助治疗蒽环类耐药的晚期乳腺癌的疗效观察[J].实用癌症杂志,2017,32(8):1358-1363.]
[4] Zhang WJ,Zeng H,Wang Q,et al.Advances of salvage therapy for metastasis triple-negative breast cancer[J].Modern Oncology,2017,25(21):3544-3547.[张为家,曾海,王茜,等.晚期三阴乳腺癌挽救治疗进展[J].现代肿瘤医学,2017,25(21):3544-3547.]
[5] Jung SY,Sereika SM,Linkov F,et al.The effect of delays in treatment for breast cancer metastasis on survival[J].Breast Cancer Res Treat,2011,130:953-964.
[6] Xu BH,Wang SS,Jiang ZF,et al.Expert consensus on maintenance treatment of advanced Chinese breast cancer[J].Chin Arch Gen Surg( Electronic Edition),2018,12(1):1-5.[徐兵河,王树森,江泽飞,等.中国晚期乳腺癌维持治疗专家共识[J].中华普通外科学文献(电子版),2018,12(1):1-5.]
[7] Lv HM,Yan M,Zhang MW,et al.Efficacy of capecitabine-based combination therapy and single-agent capecitabine maintenance therapy in patients with metastatic breast cancer[J].Chin J Cancer Res,2014,26(6):692-697.
[8] Alba E,Ruiz-Borrego M,Margeli M,et al.Maintenance treatment with pegylated liposomal doxorubicin versus observation following induction chemotherapy for metastatic breast cancer:GEICAM 2001-01 study[J].Breast Cancer Res Treat,2010,122(1):169-176.
[9] Gennari A,Amadori D,De Lena M,et al.Lack of benefit of maintenance paclitaxel in first-line chemotherapy in metastatic breast cancer[J].J Clin Oncol,2006,24(24):3912-3918.
[10] Wang ZW,Wong KK,Chew L,et al.Capecitabine as an oral chemotherapeutic agent in the treatment of refractory metastatic breast carcinoma (MBC) [J].Proc Am Soc Clin Oncol,2000,19:120.
[11] Cervantes G,Torrecillas L,Eraro AA,et al.Capecitabine (Xeloda) as treatment after failure to taxanes for metastatic breast cancer[J].Proc Am Soc Clin Oncol,2000,19:121.
[12] Wang J,Xu B,Yuan P,et al.Capecitabine combined with docetaxel versus vinorelbine followed by capecitabine maintenance medication for first-line treatment of patients with advanced breast cancer:Phase 3 randomized trial[J].Cancer,2015,121(19):3412-3421.
[13] Dong G,Jia Y,Wang X,et al.The comparison of maintenance treatment with capecitabine (CMT) and non-maintenance treatment with capecitabine (non-CMT) in patients with metastatic breast cancer[J].Int J Clin Exp Med,2015,8(5):8283-8287.
[14] Liang X,Di LJ,Song GH,et al.Capecitabine maintenance therapy for XT chemotherapy-sensitive patients with metastatic triple-negative breast cancer[J].Chin J Cancer Res,2014,26(5):550-557.
[15] Si W,Zhu YY,Li Y,et al.Capecitabine maintenance therapy in patients with recurrent or metastatic breast cancer[J].Braz J Med Biol Res,2013,46(12):1074-1081.
[16] Huang ZY,Liu FQ,Gao LC,et al.Advances in pharmacogenomics cyclophosphamide in the breast cancer therapy[J].Chin J Clin Pharmacol Ther,2014,19(10):1196-1200.[黄征宇,刘芳群,高利臣,等.乳腺癌环磷酰胺治疗的药物基因组学研究进展 [J].中国临床药理学与治疗学,2014,19(10):1196-1200.]
[17] Munzone E,Colleoni M.Clinical overview of metronomic chemotherapy in breast cancer[J].Nat Rev Clin Oncol,2015,12(11):631-644.
[18] Loeffler M,Krüger JA,Reisfeld RA.Immunostimulatory effects of low-dose cyclophosphamide are controlled by inducible nitric oxide synthase[J].Cancer Res,2005,65(12):5027-5030.
[19] Martin-Padura I,Marighetti P,Agliano A,et al.Residual dormant cancer stem-cell foci are responsible for tumor relapse after antiangiogenic metronomic therapy in hepatocellular carcinoma xenografts[J].Lab Invest,2012,92(7):952-966.
[20] Colleoni M,Rocca A,Sandri MT,et al.Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer:antitumor activity and correlation with vascular endothelial growth factor levels[J].Ann Oncol,2002,13(1):73-80.
[21] Qian Y,Ji HM,Zhang Y,et al.Clinical observation of cyclophosphamide metronomic chemotherapy plus celecoxib for advanced breast cancer[J].Journal of Basic and Clinical Oncology,2014,27(4):302-303.[钱烨,吉浩明,张燕,等.环磷酰胺节拍化疗联合塞来昔布治疗晚期乳腺癌临床观察[J].肿瘤基础与临床,2014,27(4):302-303.]