甲磺酸阿帕替尼在恶性肿瘤患者的用药特征分析

doi:10.19803/j.1672-8629.20220316

摘要/Abstract

摘要： 目的分析甲磺酸阿帕替尼在我院治疗恶性肿瘤的用药特征,为阿帕替尼的临床安全使用提供参考。方法采用回顾性调查方式,通过医院信息系统（HIS）系统汇总我院2018年1月1日~2020年12月31日期间在肿瘤内科使用阿帕替尼的患者用药特征信息。结果 69例服用阿帕替尼的患者男性49人,女性20人,平均年龄为（64.8±10.1）岁,KPS评分偏低,70分和60分居多。临床诊断集中在胃癌、结肠癌、肺癌、肝癌、胰腺癌等,Ⅳ期患者占82.6%。患者服用阿帕替尼500、250 mg 每日1次（qd）的用法比例最大,与质子泵抑制剂、中药注射剂、止吐药物、抗菌药联合使用最常见。约1/5患者影像学评价为好转和稳定,1/3患者出现进展;常见不良反应为疲劳乏力、血压升高和皮肤损伤。结论阿帕替尼在临床广泛运用于恶性肿瘤,存在超说明书用药情况,医师应高度重视合理使用,根据疗效和不良反应及时调整剂量,临床药师应做好药学监护,尽量减少药物相互作用的影响,保障患者安全用药。

关键词: 阿帕替尼, 恶性肿瘤, 用药分析, 药品不良反应, 药学监护

Abstract: Objective To analyze the characteristics of medications with apatinib mesylate in the treatment of malignant tumors, and to provide reference for the safe clinical use of apatinib. Methods A retrospective investigation was conducted to retrieve information from the HIS system on the treatment of patients who had used apatinib in the Department of Oncology in our hospital between 2018 and 2020. Results Among the 69 patients taking apatinib, 49 were males and 20 were females, with an average age of 64.8±10.1 years old. The KPS scores were low, mostly 70 and 60. Clinical diagnosis was mostly gastric cancer, colon cancer, lung cancer, liver cancer and pancreatic cancer. Stage IV patients accounted for 82.6%. The proportions of patients who took apatinib of 500 mg qd and 250 mg qd were larger. This drug was most commonly used in combination with proton pump inhibitors, traditional Chinese medicine injections, antiemetic drugs and antibacterial drugs. About 20% of the patients' conditions were improved and stable based on imaging evaluation, but one in three patients progressed. The most common adverse reactions were fatigue, elevated blood pressure and skin damage. Conclusion Apatinib is widely used in malignant tumors in clinical practice, but there are cases of off-label use. Physicians should attach importance to rational use and adjust dosage quickly according to efficacy and adverse reactions. Clinical pharmacists should provide good pharmaceutical care, minimize the influence of drug interactions, and ensure safe drug use for patients.

Key words: apatinib, malignant tumor, drug analysis, adverse drug reaction, pharmaceutical care

中图分类号:

张夏兰, 袁静, 吴斌, 秦媛媛. 甲磺酸阿帕替尼在恶性肿瘤患者的用药特征分析[J]. 中国药物警戒, 2023, 20(8): 927-932.

ZHANG Xialan, YUAN Jing, WU Bin, QIN Yuanyuan. Medications of apatinib mesylate in patients with malignant tumors[J]. Chinese Journal of Pharmacovigilance, 2023, 20(8): 927-932.

参考文献

[1] YANG C, QIN S.Apatinib targets both tumor and endothelial cells in hepatocellular carcinoma[J]. Cancer Med, 2018, 7(9): 4570-4583.
[2] MIZRAK KD, HARADA K, SHIMODAIRA Y, et al.Advanced gastric adenocarcinoma: optimizing therapy options[J]. Expert Rev Clin Pharmacol, 2017, 10(3): 263-271.
[3] FENG H, CHENG X, KUANG J, et al.Apatinib-induced protective autophagy and apoptosis through the AKT-mTOR pathway in anaplastic thyroid cancer[J]. Cell Death Dis, 2018 , 9(10): 1030.
[4] TSUKAMOTO S, ERRANI C, ANGELINI A, et al.Current Treatment considerations for osteosarcoma[J]. Metastatic at Presentation. Orthopedics, 2020, 43(5): 345-358.
[5] HU Y, QIN T, LI S, et al.Efficacy and safety of SBRT combined with camrelizumab and apatinib in hcc patients with pvtt: study protocol of a randomized controlled trial[J]. Front Oncol, 2020, 26(10):1589.
[6] ZHANG B, QI L, WANG X, et al.Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first-line treatment of advanced esophageal squamous cell carcinoma[J]. Cancer Commun,2020, 40(12): 711-720.
[7] DU WW, XU W.A study on the current situation of drug provision and use in medical institutions based on drug procurement database: Jiangsu Province as an example[J]. China Modern Applied Pharmacy, 2022, 39(6): 5.
[8] GAO WJ.International System for the Evaluation of Adverse Reactions to Chemotherapeutic Agents in Oncology - Common Adverse Reaction Terminology Standard Version 4.0[J]. Oncology, 2012, (2): 142-144.
[9] Thyroid Cancer Expert Committee. Expert consensus on the management of adverse reactions to targeted drugs in iodine-refractory differentiated thyroid cancer (2018 version)[J]. Chinese Journal of Cancer, 2018, 28(7): 545-553.
[10] HUANG F, WANG XX, LUO SJ, et al.Treatment and prognosis of adolescent osteosarcoma[J]. Journal of Practical Cancer, 2014, 29(2): 196-198.
[11] National Health and Wellness Commission of the People's Republic of China. Ovarian cancer treatment specification (2018 edition)[J]. Electronic Journal of Comprehensive Cancer Therapy, 2019, 5(2):10.
[12] Expert Committee on Rational Use of Drugs, National Health and Family Planning Commission. Guide to the rational use of drugs for gastrointestinal malignancies[J]. Chinese Licensed Pharmacist, 2017, (9): 5-54.
[13] LIANG LJ, HU CX, WEN YX, et al.Apatinib combined with local irradiation leads to systemic tumor control via reversal of immunosuppressive tumor microenvironment in lung cancer[J].Cancer Res Treat, 2020, 52(2): 406-418.
[14] ZHAO S, REN S, JIANG T, et al.Low-dose apatinib optimizes tumor microenvironment and potentiates antitumor effect of PD-1/PD-L1 Blockade in Lung Cancer[J]. Cancer Immunol Res, 2019, 7(4): 630-643.
[15] QIU H, LI J, LIU Q, et al.Apatinib, a novel tyrosine kinase inhibitor, suppresses tumor growth in cervical cancer and synergizes with Paclitaxel[J]. Cell Cycle, 2018, 17(10):1235-1244.
[16] YU M, GAO Z, DAI X, et al.Population pharmacokinetic and covariate analysis of apatinib, an oral tyrosine kinase inhibitor, in healthy volunteers and patients with solid tumors[J]. Clin Pharmacokinet, 2017, 56(1): 65-76.
[17] CHEN J, WANG J, MIAO Q.Careful dose modification of apatinib as third or further-line treatment in advanced gastric cancer patients with poor performance status[J]. Medicine. 2019, 98(45):17890.
[18] DU Y, CAO Q, JIANG C, et al.Effectiveness and safety of low-dose apatinib in advanced gastric cancer: A real-world study[J]. Cancer Med. 2020 , 9(14): 5008-5014.
[19] HUANG M, GONG Y, ZHU J, et al.A phase I dose-reduction study of apatinib combined with pemetrexed and carboplatin in untreated EGFR and ALK negative stage IV non-squamous NSCLC[J]. Invest New Drugs, 2020, 38(2): 478-484.
[20] LIU X, ZHANG Y, CHEN Q, et al.Pharmacokinetic Drug Interactions of Apatinib With Rifampin and Itraconazole[J]. Clin Pharmacol, 2018, 58(3): 347-356.
[21] ZHU YT, TENG Z, ZHANG YF, et al.Effects of apatinib on the pharmacokinetics of nifedipine and warfarin in patients with advanced solid tumors[J]. Drug Des Devel Ther. 2020, 20(14): 1963-1970.
[22] XUE JM, ASTÈRE M, ZHONG MX, et al. Efficacy and safety of apatinib treatment for gastric cancer, hepatocellular carcinoma and non-small cell lung cancer: a meta-analysis[J]. Onco Targets Ther, 2018, 21(11): 6119-6128.
[23] WANG X, YU J, YANG M, et al.Safety and effectiveness of apatinib in patients with previously treated metastatic gastric cancer: a sub-analysis from the real-world study of apatinib for gastric cancer treatment (AHEAD-G202)[J] . Cancer Res, 2020, 10(3): 987-996.
[24] GOU M, SI H, ZHANG Y, et al.Efficacy and safety of apatinib in patients with previously treated metastatic colorectal cancer: a real-world retrospective study[J]. Sci Rep, 2018, 8(1): 4602.
[25] LI C, TANG T, WANG W.Combination use of tegafur and apatinib as first-line therapy in treatment of advanced gastric cancer: a single-blinded randomized study[J]. Gastroenterol Res Pract, 2020,4(6):1-6.
[26] WU Q, FU Y, WEN W, et al.Efficacy and prognosis analyses of apatinib combined with S-1 in third-line chemotherapy for advanced gastric cancer[J]. BUON, 2020, 25(2): 987-994.
[27] LENG J, LI DR, HUANG LM, et al.Apatinib is effective as third-line and more treatment of advanced metastatic non-small-cell lung cancer: A retrospective analysis in a real-world setting[J]. Medicine (Baltimore), 2019, 98(36): 16967.
[28] ZHU A, YUAN P, WANG J, et al.Apatinib combined with chemotherapy in patients with previously treated advanced breast cancer: An observational study[J]. Oncol Lett, 2019, 17(6): 4768-4778.
[29] LI N, BAI C, ZHANG R, et al.Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer[J]. Transl Oncol, 2021, 14(2): 309-315.
[30] GENG N, DING CM, LIU ZK, et al.Influence of VEGFR2 gene polymorphism on the clinical outcomes of apatinib for patients with chemotherapy-refractory extensive-stage SCLC: a real-world retrospective study[J]. Clin Oncol, 2021, 26(4): 670-683.
[31] PENG W, ZHANG F, WANG Z, et al.Multicenter, prospective study of apatinib in advanced gastric cancer: a real-world study from China[J]. Cancer Manag Res, 2020, 6(12): 6977-6985.
[32] ZHANG Y, HAN C, LI J, et al.Efficacy and safety for Apatinib treatment in advanced gastric cancer: a real world study[J]. Sci Rep 2017 , 7(1): 13208.