甲磺酸阿帕替尼联合化疗在晚期乳腺癌患者治疗中的临床应用

doi:10.13481/j.1671-587x.20190530

摘要/Abstract

摘要： 目的：观察甲磺酸阿帕替尼（简称阿帕替尼）联合化疗在多线治疗失败的晚期乳腺癌患者中的临床疗效和安全性，阐明阿帕替尼在晚期乳腺癌患者治疗中的意义。方法： 25例晚期乳腺癌患者均为多线治疗进展者，其中三线治疗者5例（20%），四线治疗者7例（28%），五线及以上治疗者13例（52%）。所有患者均采用阿帕替尼联合化疗，根据病情及既往用药情况选择化疗方案。阿帕替尼剂量为250~500 mg，每日1次，口服，直至疾病进展或不能耐受发生不良反应为止。采用实体瘤疗效评价标准1.1（RECIST1.1）评价疗效，包括客观缓解率（ORR）、临床获益率（CBR）和无进展生存期（PFS），采用国家通用研究所毒副反应标准4.0（NCI-CTC4.0）评价不良反应。结果： 25例晚期乳腺癌患者中位治疗线数为五线，总ORR为12%（3/25），CBR为52%（13/25），中位无进展生存期（mPFS）为6.00个月。治疗线数评价，三线治疗的5例患者中，2例疾病稳定（SD），CBR为40%（2/5）；四线治疗的7例患者中，2例部分缓解（PR），2例SD，CBR为57%（4/7）；五线及以上治疗的13例患者中，1例PR，6例SD，CBR为54%（7/13）。病理类型评价，三阴型患者中，3例SD，CBR为60%（3/5）；12例腔上皮型（Luminal型）患者中，1例PR，2例SD，CBR为25%（3/12）；HER-2阳性患者中，1例PR，6例SD，CBR为88%（7/8）。50岁及以上组患者近期疗效优于50岁以下组（P<0.05），其余不同临床病理参数患者之间近期疗效比较差异无统计学意义（P>0.05）。接受阿帕替尼联合化疗患者耐受性良好，不良反应多为1或2级，主要表现为乏力、手足综合征、肝功能异常、低蛋白血症、贫血、食欲不振、血压升高和蛋白尿，其中最常见不良反应为乏力（80%），其次为低蛋白血症（60%）、手足综合征（60%）和肝功能异常（60%）。结论：阿帕替尼联合化疗用于多线治疗进展的晚期乳腺癌患者仍有较好疗效，不良反应可耐受。

关键词: 乳腺肿瘤, 甲磺酸阿帕替尼, 化学疗法, 客观缓解率, 临床获益率, 无进展生存期

Abstract: Objective:To observe the clinical efficacy and safety of apatinib combined with chemotherapy in the patients with advanced breast cancer after failed multi-line therapy, and to clarify the siginificance of apatinib in the treatment of the patients with advanced breast cancer. Methods:Twenty-five patients with advanced breast cancer were treated with multi-line therapy,among them 5 (20%) patients were in the third-line treatment, 7 (28%) patients were in the fourth-line treatment, and 13 (52%) patients were in the fifth-line treatment and above. All patients were treated with apatinib in combination with chemotherapy, and the chemotherapy regimen was selected based on the condition and previous medication. Apatinib 250-500 mg was given orally once a day, until the disease progresses occured or the patients could not tolerate the adverse reactions. The efficacies, including the objective response rate(ORR), the clinical benefit rate(CBR), and progression-free survival (PFS), were evaluated by RECIST 1.1. The adverse reactions were evaluated by NCI-CTC 4.0. Results:The median number of treatment lines of the patients with breast cancer was fifth-line, the total ORR was 12% (3/25), the CBR was 52% (18/25), and the median progression-free survival (mPFS) was 6.00 months. Among the 5 patients with third-line therapy, 2 patients were stable disease(SD) and the CBR was 40% (2/5); among the 7 patients received the fourth-line therapy, 2 patients were partial response(PR), 2 patients were SD, and the CBR was 57%(4/7); among the 13 patients received firth-line therapy, 1 patient was PR, 6 cases were SD, and the CBR was 54% (7/13). According to the pathological type, among 5 patients of triple-negative type, 3 patients were SD, the CBR was 60% (3/5); among 12 patients of Luminal type,1 patients was PR, 2 patients were SD, and the CBR was 25% (3/12); among 8 patients of HER-2 positive type, there were 2 patients acheived PR, 5 patients acheived SD, and the CBR was 88% (7/8). The short-term efficacy of the patients in 50 years old and over group was better than that of the patients in below 50 years old group (P<0.05). There were no significant differences in the short-term efficacies between the other factors (P>0.05). Moreover, the patients treated with apatinib combined with chemotherapy had good tolerance, and the main adverse reactions were fatigue, hand-foot syndrome, hepatic insufficiency, hypoproteinemia, anemia, anepi-thymia,hypertension,and proteinuria;mainly in grade 1 or grade 2;the most common adverse reactionswere fatigue(80%),hypoproteinemia(60%),hand-foot syndrome(60%),and hepatic insufficiency(60%). Conclusion:Apatinib mesylate combined with chemotherapy is effective in the treatment of the advanced breast cancer patients failed in multi-line therapy and the patients can tolerate the adverse reactions.

Key words: breast neoplasms, apatinib, chemotherapy, objective response rate, clinical benefit rate, progression-free survival

中图分类号:

R737.9

王爽, 康丽花, 关萌, 王磊, 李贝贝, 赵月, 宋艳秋, 杨婷婷. 甲磺酸阿帕替尼联合化疗在晚期乳腺癌患者治疗中的临床应用[J]. 吉林大学学报(医学版), 2019, 45(05): 1152-1158.

WANG Shuang, KANG Lihua, GUAN Meng, WANG Lei, LI Beibei, ZHAO Yue, SONG Yanqiu, YANG Tingting. Clinical application of apatinib mesylate combined with chemotherapy in treatment of patients with advanced breast cancer[J]. Journal of Jilin University(Medicine Edition), 2019, 45(05): 1152-1158.

参考文献

[1] 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.
[2] 高德宗. 激素受体阳性晚期转移性乳腺癌的内分泌治疗[J]. 中华乳腺病杂志:电子版, 2018, 12(2):69-72.
[3] LIN M I, SESSA W C. Antiangiogenic therapy:creating a unique "window"of opportunity[J]. Cancer Cell, 2004,6(6):529-531.
[4] 朱安婕,袁芃. 抗血管生成酪氨酸激酶抑制剂在晚期乳腺癌中的应用[J]. 中华乳腺病杂志:电子版,2018, 12(4):234-237.
[5] 王雅婕,胡毅. 甲磺酸阿帕替尼治疗晚期恶性肿瘤的研究进展[J]. 解放军医学院学报,2018, 39(6):542-545,553.
[6] XUE J, ASTERE M, ZHONG M, et al. Efficacy and safety of apatinib treatment for gastric cancer, hepatocellular carcinoma and non-small cell lung cancer:a meta-analysis[J].Oncotargets Ther, 2018, 11:6119-6128.
[7] 桑蝶,张频,李青,等. 白蛋白结合型紫杉醇治疗多线化疗失败乳腺癌的疗效及安全性分析[J]. 临床药物治疗杂志,2018, 16(7):28-33.
[8] EISENHAUER E A, THERASSE P, BOGAERTS J, et al. New response evaluation criteria in solid tumours:Revised RECIST guideline (version 1.1)[J]. Eur J Cancer,2009,45(2):228-247.
[9] HUGHES R. NCI-CTC vs TNS:which tool is better for grading the severity of chemotherapy-induced peripheral neuropathy?[J]. Nat Clin Pract Neurol,2008, 4(2):68-69.
[10] ZHOU Z, YAO H, HU H. Disrupting tumor angiogenesis and "the hunger games" for breast cancer[J]. Adv Exp Med Biol, 2017, 1026:171-195.
[11] HU X C, CAO J, HU W W, et al. Multicenter phase Ⅱ study of Apatinib in non-triple-negative metastatic breast cancer[J]. BMC Cancer,2014, 14:820.
[12] HU X, ZHANG J, XU B, et al. Multicenter phase Ⅱ study of apatinib, a novel VEGFR inhibitor in heavily pretrnted patients with metastatic triple-negative breast cancer[J]. Int J Cancer, 2014, 135(8):1961-1969.
[13] SEIDMAN A D. Gemcitabine as single-agent therapy in the management of advanced breast cancer[J]. Oncology(Williston Park),2001, 153(2 Suppl 3):11-14.
[14] FUMOLEAU P, BLUM J L, REICHARDT P. Weekly vinorelbine is an effective palliative regimen after failure with anthracyclinels and taxanes in metastatic breast carcinoma[J]. Cancer. 2003, 98(6):1325-1326.
[15] SONG Y Q, LIU B L, GUAN M, et al. Successful treatment using apatinib in intractable brain edema:A case report and literatures review[J]. Cancer Biol Ther,2018,19(12):1093-1096.
[16] 马莉,刘妍妍,糜志远. 阿帕替尼治疗乳腺癌的研究进展[J]. 大医生,2018(4):160-162.
[17] ZHANG H J. Apatinib for molecular targeted therapy in tumor[J]. Drug Des Devel Ther,2015, 9:6075-6081.
[18] 陈玲娟,伍钢,董晓荣,等. 阿帕替尼二线及二线以上治疗晚期肺癌26例[J]. 医药导报,2018, 37(5):551-554.
[19] 时佳琪,刘超,张艳桥,等. 甲磺酸阿帕替尼治疗恶性肿瘤的临床不良反应分析[J]. 中国肿瘤临床,2018(4):191-195.
[20] QIN S K. Apatinib in Chinese patients with advanced hepatocellular carcinoma:A phase Ⅱ randomized, open-label trial[J]. J Clin Oncol, 2014, 32(15_Suppl):4019.
[21] LI J, QIN S K, XU J M, et al. Apatinib for chemotherapy-refractory advanced metastatic gastric cancer:Results from a randomized, placebo-controlled, parallel-arm, phase Ⅱ trial[J]. J Clin Oncol, 2013, 31(26):3219-3225.