目的 评估临床药师参与多学科合作的骨肉瘤患者大剂量甲氨蝶呤(high dose methotrexate, HD-MTX)药学监护的工作效果。方法 纳入2018年5月至2020年10月期间在我院进行HD-MTX化疗的骨肉瘤患者作为干预组,采用多学科合作模式对其进行药学监护;同时选取2015年3月至2018年4月期间进行HD-MTX化疗的骨肉瘤患者作为对照组,对两组患者的MTX血药浓度、血药浓度达标率、MTX排泄延迟发生率、亚叶酸钙(leucovorin calcium, LV)解救方案调整情况、不良反应发生率、住院时间及药物治疗费用等指标进行统计分析。结果 与对照组相比,干预组患者在用药后各监测点血药浓度有下降趋势,血药浓度达标率明显提高,MTX排泄延迟发生率明显下降,P值均小于0.05。LV解救方案正确调整比率明显提高。急性肾功能损伤、肝酶升高以及中性粒细胞减少等不良反应发生率均明显下降,Ⅲ级及以上的严重不良反应发生率也明显降低,P值均小于0.05。干预组患者的平均住院日明显缩短(5.76 vs 6.62,P=0.002),药物治疗费用也较对照组大幅降低(7 165.0 vs 14 628.4,P=0)。结论 采用多学科合作模式进行骨肉瘤患者HD-MTX药学监护可以有效提高用药安全性,降低治疗成本。
Abstract
OBJECTIVE To evaluate the effect of multi-disciplinary cooperative pharmaceutical care of high dose methotrexate (HD-MTX) in patients with osteosarcoma. METHODS Osteosarcoma patients treated with HD-MTX chemotherapy were enrolled to receive multi-disciplinary cooperative pharmaceutical care as intervention group during 2018.05-2020.10. Osteosarcoma patients who meet the inclusion criteria during 2015.03-2018.04 were enrolled as control group and analyzed. MTX serum concentration, MTX concentration compliance rate, incidence of appropriate leucovorin calcium (LV) prescription, rate of adverse effects, length of hospitalization and cost of drug treatment were recorded and calculated to compare the outcomes of each group. RESULTS MTX concentration compliance rate in intervention group were significantly higher than control group, while the incidence of MTX elimination delay were obviously reduced, P values were both less than 0.05. Higher incidence of appropriate leucovorin calcium (LV) prescription was also found in intervention group. The incidence of drug adverse reactions such as renal dysfunction, elevated liver enzymes and neutropenia decreased significantly. The incidence of severe adverse events (Grade Ⅲ and above) was also significantly reduced, P values was less than 0.05. A statistically significant decrease in length of hospitalization and cost of drug treatment were observed in intervention group compared with control group. CONCLUSION The implementation of multi-disciplinary cooperative pharmaceutical care of HD-MTX in patients with osteosarcoma could effectively improve the safety of MTX medication and reduce the cost of treatment.
关键词
大剂量甲氨蝶呤 /
骨肉瘤 /
药学监护 /
多学科合作
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Key words
high dose methotrexate /
osteosarcoma /
pharmaceutical care /
multi-disciplinary-cooperation
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中图分类号：
R969.3
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参考文献
[1] HOWARD S C, MCCORMICK J, PUI C H, et al. Preventing and managing toxicities of high-dose methotrexate [J]. Oncologist, 2016, 21(12):1471-1482.
[2] ZELCER S, KELLICK M, WEXLER L H, et al. The memorial sloan kettering cancer center experience with outpatient administration of high dose methotrexate with leucovorin rescue [J]. Pediatr Blood Cancer, 2008, 50(6):1176-1180.
[3] PANG L, CHEN C, ZHU X, et al. Advance of the influence of metabolic enzyme and transporter polymorphisms in pharnacokinetics and toxicity of high-dose methotrexate [J]. Chin Pharm J(中国药学杂志), 2016, 51(1):10-14.
[4] CERMINARA Z, DUFFY A, NISHIOKA J, et al. A single center retrospective analysis of a protocol for high-dose methotrexate and leucovorin rescue administration [J]. J Oncol Pharm Pract, 2019, 25(1):76-84.
[5] MATTA S F, GIESELMAN L A, MANCINI R S. A single-center qualitative study evaluating the safety and efficacy of a pharmacist-driven protocol for high-dose methotrexate management [J]. J Oncol Pharm Pract, 2020, 27(3):588-595.
[6] XIA F, GAO J, XIE C, et al. Role of the establishment of protocol in the prevention of high-dose methotrexate induced acute kidney injury [J]. Adverse Drug React J(药物不良反应杂志), 2017,19(4):277-281.
[7] RELLING M V, FAIRCLOUGH D, AYERS D, et al. Patient characteristics associated with high-risk methotrexate concentrations and toxicity [J]. J Clin Oncol, 1994, 12(8):1667-1672.
[8] AL QUTEIMAT O M, AL BADAINEH M A. Practical issues with high dose methotrexate therapy [J]. Saudi Pharm J, 2014, 22(4):385-387.
[9] JOERGER M, HUITEMA A D R, VAN DEN BONGARD H, et al. Determinants of the elimination of methotrexate and 7-hydroxy-methotrexate following high dose infusional therapy to cancer patients[J]. Br J Clin Pharmacol, 2006, 62(1): 71-80.
[10] WANG X, SONG Y, WANG J, et al. Effect of proton pump inhibitors on high-dose methotrexate elimination: a systematic review and meta-analysis [J]. Int J Clin Pharm. 2020;42(1):23-30.
[11] TRAN H X, HERRINGTON J D. Effect of ceftriaxone and cefepime on high-dose methotrexate clearance [J]. J Oncol Pharm Pract, 2016, 22(6):801-805.
[12] PANG L, LIU L M, ZHAO L M. Research progress in influence factors of excretion delay of high-dose methotrexate [J]. Chin Pharm J(中国药学杂志), 2013, 48(22):1892-1895.
[13] CSCO. High dose methotrexate with leucovorin calcium rescue therapy for malignant tumors, a expert consensus [J]. Chin J Clin Oncol (中国肿瘤临床), 2019, 46(15):761-767.
[14] HEGYI M, GULÁCSI A, CSÁGOLY E, et al. Clinical relations of methotrexate pharmacokinetics in the treatment for pediatric osteosarcoma [J]. J Cancer Res Clin Oncol, 2012, 138(10):1697-1702.
[15] VAN DER BEEK J N, OOSTEROM N, PIETERS R, et al. The effect of leucovorin rescue therapy on methotrexate-induced oral mucositis in the treatment of paediatric ALL: A systematic review [J]. Crit Rev Oncol Hematol, 2019, 142:1-8.
[16] MA K, ZHAO H T, ZHANG Q. A comparative study of the toxic side reactions caused by high dose methotrexate chemotherapy [J]. Chin J Clin Bone Joint (中国骨与关节杂志), 2012, 1(2):132-135.
[17] LIN F, WANG C Y, TANG L N, et al. Risk factors associated with liver damage induced by high-dose methotrexate treatment of osteosarcoma [J]. Tumor(肿瘤), 2014, 34(5):450-453.
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脚注
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基金
国家自然科学基金青年项目资助(81703474)
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