Efficacy and Safety of Different Infusion Schedules of High-dose Methotrexate in the Treatment of Osteosarcoma ：A Meta- analysis
- VernacularTitle:大剂量甲氨蝶呤不同输注方案治疗骨肉瘤疗效和安全性的Meta分析
- Author:
Zhencheng HUANG
1
,
2
,
3
;
Zaiwei SONG
1
,
2
,
3
;
Rongsheng ZHAO
1
Author Information
1. Dept. of Pharmacy，Peking University Third Hospital，Beijing 100191，China
2. Dept. of Pharmacy Administration and Clinical Pharmacy，School of Pharmaceutical Sciences，Peking University，Beijing 100191，China
3. Center for Drug Evaluation，Peking University Health Science Center，Beijing 100191，China
- Publication Type:Journal Article
- Keywords:
High-dose;
Methotrexate;
Osteosarcoma;
Infusion schemes;
Efficacy;
Safety;
Meta-analysis
- From:
China Pharmacy
2019;30(13):1835-1841
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE： To systematically evaluate the efficacy and safety for different infusion schemes of large-dose （＞500 mg/m2） of methotrexate in the treatment of osteosarcoma， and to provide evidence-based reference for clinical treatment. METHODS： Retrieved from Medline， Embase， clinicaltrials.gov， CJFD， Wanfang database and CBM database， observational studies and randomized/non-randomized controlled trials about therapeutic efficacy and safety for different infusion schemes （different doses and infusion time） of large-dose of methotrexate in the treatment of osteosarcoma were included during the establishment of the database to Mar. 2018. After data extraction and quality evaluation with methodological evaluation index of the Newcastle-Ottawa scale， Cochrane 5.1.0 bias risk evaluation tool and non-randomized controlled trials， Meta-analysis or descriptive analysis for blood drug concentration （c）， related toxicity （e.g. incidence of hepatotoxicity， incidence of hemotoxicity） were performed by using Rev Man 5.3 software. RESULTS： Totally 5 studies were included， involving 310 cases. Results of Meta-analyses indicated c0 h [MD＝－240.11， 95％CI（－271.47， －208.75）， P＜0.001]， c24 h [MD＝－0.09， 95％CI （－0.11， 0.08）， P＜0.001]， c48 h [MD＝－0.07， 95％CI （－0.10， －0.05）， P＜0.001]， c72 h [MD＝－0.05， 95％CI （－0.06， －0.03）， P＜0.001] and the incidence of liver toxicity [OR＝0.26， 95％CI （0.10， 0.67）， P＜0.005] in 8 g/m2 group were significantly lower than 10 g/m2 group. Results of descriptive analysis showed that when both groups were given 8 g/m2， c24 h of patients with 2 and 4 h infusion time was significantly lower than that of patients with 6 h infusion time. The incidence of leukopenia and thrombo- cytopenia in 8 g/m2 group was significantly lower than 10 g/m2 group. CONCLUSIONS： In the treatment of osteosarcoma with high-dose of methotrexate， appropriate dosage reduction （e.g. 8 g/m2） and appropriate prolongation of infusion time （e.g. 6 h） may lead to a better efficacy and safety.
