Zaiwei Song1,2,3, Yang Hu1,2,3, Shuang Liu1,2,3, Guanru Wang1,2,3, Suodi Zhai1,2,3, 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 Zhan25,26, Bikui Zhang27, Lingli Zhang28, Yanhua Zhang29, Wei Zhang30, Limei Zhao31, Libo Zhao22, Jiancun Zhen30, Huyong Zheng21, Zhu Zhu32, Dan Jiang1,2,3, Zhencheng Huang1,2,3, Zhiyuan Tan1,2,3, Qiaonan Lin1,2,3, Rongsheng Zhao1,2,3. 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.
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.
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.