Medication therapy of high-dose methotrexate: An evidence-based practice guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society

doi:10.1111/bcp.15134

. 2022 May;88(5):2456-2472.

doi: 10.1111/bcp.15134. Epub 2022 Feb 8.

Medication therapy of high-dose methotrexate: An evidence-based practice guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society

Zaiwei Song^{1

2

3}, Yang Hu^{1

2

3}, Shuang Liu^{1

2

3}, Guanru Wang^{1

2

3}, Suodi Zhai^{1

2

3}, Xianglin Zhang⁴, Youping Li⁵, Guanhua Du⁶, Yuankai Shi⁷, Yaolong Chen⁸, Mei Dong⁹, Ruichen Guo¹⁰, Wei Guo¹¹, Hongbing Huang¹², Xiaojun Huang¹³, Hongmei Jing¹⁴, Xiaoyan Ke¹⁴, Guohui Li¹⁵, Liyan Miao¹⁶, Xiaohui Niu¹⁷, Feng Qiu¹⁸, Jingnan Shen¹⁹, Jingyan Tang²⁰, Tianyou Wang²¹, Xiaoling Wang²², Zhuo Wang²³, Jiuhong Wu²⁴, Siyan Zhan^{25

26}, Bikui Zhang²⁷, Lingli Zhang²⁸, Yanhua Zhang²⁹, Wei Zhang³⁰, Limei Zhao³¹, Libo Zhao²², Jiancun Zhen³⁰, Huyong Zheng²¹, Zhu Zhu³², Dan Jiang^{1

2

3}, Zhencheng Huang^{1

2

3}, Zhiyuan Tan^{1

2

3}, Qiaonan Lin^{1

2

3}, Rongsheng Zhao^{1

2

3}

Affiliations

¹ Department of Pharmacy, Peking University Third Hospital, Beijing, China.
² Institute for Drug Evaluation, Peking University Health Science Center, Beijing, China.
³ Therapeutic Drug Monitoring and Clinical Toxicology Center, Peking University, Beijing, China.
⁴ Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China.
⁵ Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
⁶ Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
⁷ Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer, Beijing, China.
⁸ Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
⁹ Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, China.
¹⁰ Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China.
¹¹ Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, China.
¹² Department of Pharmacy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
¹³ Peking University Institute of Hematology, Peking University People's Hospital, National Clinical Research Center for Hematologic Disease, Beijing, China.
¹⁴ Department of Hematology, Peking University Third Hospital, Beijing, China.
¹⁵ Department of Pharmacy, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer, Beijing, China.
¹⁶ Department of Clinical Pharmacology, First Affiliated Hospital of Soochow University, Suzhou, China.
¹⁷ Department of Orthopedic Oncology, Beijing Jishuitan Hospital and Fourth Medical College of Peking University, Beijing, China.
¹⁸ Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
¹⁹ Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
²⁰ Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Key Lab of Pediatric Hematology & Oncology of China Ministry of Health, Shanghai, China.
²¹ Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
²² Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing, China.
²³ Department of Pharmacy, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
²⁴ Pharmacy Department, The 306th Hospital of PLA, Beijing, China.
²⁵ Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
²⁶ Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China.
²⁷ Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China.
²⁸ Department of Pharmacy/Evidence-Based Pharmacy Centre, West China Second University Hospital, Sichuan University, Chengdu, China.
²⁹ Department of Pharmacy, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China.
³⁰ Department of Pharmacy, Jishuitan Hospital and Fourth Medical College of Peking University, Beijing, China.
³¹ Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China.
³² Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

PMID: 34729817
DOI: 10.1111/bcp.15134

Free article

Medication therapy of high-dose methotrexate: An evidence-based practice guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society

Zaiwei Song et al. Br J Clin Pharmacol. 2022 May.

Free article

. 2022 May;88(5):2456-2472.

doi: 10.1111/bcp.15134. Epub 2022 Feb 8.

Authors

Affiliations

¹ Department of Pharmacy, Peking University Third Hospital, Beijing, China.
² Institute for Drug Evaluation, Peking University Health Science Center, Beijing, China.
³ Therapeutic Drug Monitoring and Clinical Toxicology Center, Peking University, Beijing, China.
⁴ Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China.
⁵ Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
⁶ Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
⁷ Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer, Beijing, China.
⁸ Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
⁹ Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, China.
¹⁰ Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China.
¹¹ Musculoskeletal Tumor Center, Peking University People's Hospital, Beijing, China.
¹² Department of Pharmacy, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
¹³ Peking University Institute of Hematology, Peking University People's Hospital, National Clinical Research Center for Hematologic Disease, Beijing, China.
¹⁴ Department of Hematology, Peking University Third Hospital, Beijing, China.
¹⁵ Department of Pharmacy, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Cancer Center/National Clinical Research Center for Cancer, Beijing, China.
¹⁶ Department of Clinical Pharmacology, First Affiliated Hospital of Soochow University, Suzhou, China.
¹⁷ Department of Orthopedic Oncology, Beijing Jishuitan Hospital and Fourth Medical College of Peking University, Beijing, China.
¹⁸ Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
¹⁹ Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
²⁰ Department of Hematology/Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Key Lab of Pediatric Hematology & Oncology of China Ministry of Health, Shanghai, China.
²¹ Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
²² Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing, China.
²³ Department of Pharmacy, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
²⁴ Pharmacy Department, The 306th Hospital of PLA, Beijing, China.
²⁵ Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
²⁶ Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China.
²⁷ Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China.
²⁸ Department of Pharmacy/Evidence-Based Pharmacy Centre, West China Second University Hospital, Sichuan University, Chengdu, China.
²⁹ Department of Pharmacy, Peking University Cancer Hospital and Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China.
³⁰ Department of Pharmacy, Jishuitan Hospital and Fourth Medical College of Peking University, Beijing, China.
³¹ Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China.
³² Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

PMID: 34729817
DOI: 10.1111/bcp.15134

Abstract

Aims: A lot of medication risks related to high-dose methotrexate (HDMTX) therapy still remain to be identified and standardized. This study aims to establish an evidence-based practice guideline for individualized medication of HDMTX.

Methods: The practice guideline was launched by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. The guideline was developed following the WHO handbook for guideline development and the methodology of evidence-based medicine (EBM). The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2017CN021). Systematic reviews were conducted to synthesize available evidence. A multicentre cross-sectional study was conducted using questionnaires to evaluate patients' perception and willingness concerning individualized medication of HDMTX. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the quality of evidence and to grade the strength of recommendations.

Results: Multidisciplinary working groups were included in this guideline, including clinicians, pharmacists, methodologists, pharmacologists and pharmacoeconomic specialists. A total of 124 patients were involved to integrate patient values and preferences. Finally, the guideline presents 28 recommendations, regarding evaluation prior to administration (renal function, liver function, pleural effusion, comedications, genetic testing), pre-treatment and routine dosing regimen, therapeutic drug monitoring (necessity, method, timing, target concentration), leucovorin rescue (initial timing, dosage regimen and optimization), and management of toxicities. Of these, 12 are strong recommendations.

Conclusions: We developed an evidence-based practice guideline with respect to HDMTX medication using a rigorous and multidisciplinary approach. This guideline provides comprehensive and practical recommendations involving the whole process of HDMTX administration to health care providers.

Keywords: GRADE; guideline; methotrexate; therapeutic drug monitoring.

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References

REFERENCES

1. Jolivet J, Cowan KH, Curt GA, Clendeninn NJ, Chabner BA. The pharmacology and clinical use of methotrexate. N Engl J Med. 1983;309(18):1094-1104.
1. Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and managing toxicities of high-dose methotrexate. Oncologist. 2016;21(12):1471-1482.
1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Acute Lymphoblastic Leukemia (Version 1), 2021. http://nccn.org/. Accessed April 1, 2021.
1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (Version 3), 2021. http://nccn.org/. Accessed April 1, 2021.
1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Bone Cancer (Version 1), 2021. http://nccn.org/. Accessed April 1, 2021.

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[1] Jolivet J, Cowan KH, Curt GA, Clendeninn NJ, Chabner BA. The pharmacology and clinical use of methotrexate. N Engl J Med. 1983;309(18):1094-1104.

[2] Jolivet J, Cowan KH, Curt GA, Clendeninn NJ, Chabner BA. The pharmacology and clinical use of methotrexate. N Engl J Med. 1983;309(18):1094-1104.

[3] Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and managing toxicities of high-dose methotrexate. Oncologist. 2016;21(12):1471-1482.

[4] Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and managing toxicities of high-dose methotrexate. Oncologist. 2016;21(12):1471-1482.

[5] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Acute Lymphoblastic Leukemia (Version 1), 2021. http://nccn.org/. Accessed April 1, 2021.

[6] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Acute Lymphoblastic Leukemia (Version 1), 2021. http://nccn.org/. Accessed April 1, 2021.

[7] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (Version 3), 2021. http://nccn.org/. Accessed April 1, 2021.

[8] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (Version 3), 2021. http://nccn.org/. Accessed April 1, 2021.

[9] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Bone Cancer (Version 1), 2021. http://nccn.org/. Accessed April 1, 2021.

[10] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Bone Cancer (Version 1), 2021. http://nccn.org/. Accessed April 1, 2021.

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Medication therapy of high-dose methotrexate: An evidence-based practice guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society

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Medication therapy of high-dose methotrexate: An evidence-based practice guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society

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