Safety and efficacy of Compound Huangdai Tablets combined with all-trans retinoic acid for treatment of acute promyelocytic leukemia: Clinical evidence and potential mechanisms

Qian-qian Huang a，Tao Wang a，Yan Xiong a，Li-ping Qu a，Qiao-zhi Yin b，Wen-jun Zou a; Qian-qian Huang a; Tao Wang a; Yan Xiong a; Li-ping Qu a; Qiao-zhi Yin b; Wen-jun Zou a

Archive > Volume 14 Issue 1 > 2022,14(1):154-165. DOI:10.1016/j.chmed.2021.09.004 Prev Next

Original articles

Safety and efficacy of Compound Huangdai Tablets combined with all-trans retinoic acid for treatment of acute promyelocytic leukemia: Clinical evidence and potential mechanisms

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Abstract:

Objective: To evaluate the safety and efficacy of Compound Huangdai Tablets (Realgar-Indigo Naturalis formula, RIF) combined with all-trans retinoic acid (ATRA) to treat acute promyelocytic leukemia (APL). Methods: This study was registered in PROSPERO (CRD42018108118). The relevant literatures on RIF treatment of APL were systematically searched in the following databases: China National Knowledge Infrastructure, Wanfang, VIP Medical Information System, Chinese Biomedical Database, EMBASE, Cochrane Library, and PubMed. The quality of the included studies was evaluated and Review Manager 5.3 software and Stata 13.0 software were used to perform the Meta-analysis. In addition, this study will use the method of network pharmacology to conduct a preliminary exploration of the mechanism of RIF on APL. Results: The study included 12 studies involving totally of 775 APL patients. The Meta-analysis showed that there was no significant difference (P ＞ 0.05) between the RIF group and the arsenic trioxide (ATO) group for primary outcomes, secondary outcomes apart from liver dysfunction. The incidence of liver dysfunction (P = 0.006) in the RIF group were significantly lower than those in the ATO group. In addition, the cost of maintenance therapy in the RIF group was significantly lower (P ＜ 0.05) than the ATO group. Besides, the active ingredients in RIF mainly act on targets proteins such as ACHE, NCOA2, RXRA, then regulate TP53 Regulates Transcription of Cell Cycle Genes, nuclear receptor transcription pathway and other ways to play a role in treating APL. Conclusion: There was no significant difference in efficacy of oral RIF combined with ATRA compared with intravenous ATO combined with ATRA for the treatment of APL. The oral RIF exposed patients to less risk, offered more convenience and had lower prices. RIF can treat APL by multi-target and multi-pathway interventions that inducing apoptosis of APL cells and inhibiting the proliferation of APL cells, and so on. Therefore, oral RIF in the treatment of APL is worthy of further research and development.

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This work was funded by the China Postdoctoral Science Foundation Project (No.2018M633332)

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