The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, PR China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Department of Oncology, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, PR China.
Department of Acupuncture, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510120, PR China.
J Ethnopharmacol. 2023 Nov 15;316:116734. doi: 10.1016/j.jep.2023.116734. Epub 2023 Jun 7.
Processed from natural minerals, arsenic trioxide (ATO) as an ancient Chinese medicine has been used to treat diseases for over 2000 years. And it was applied to treat acute promyelocytic leukemia (APL) since the 1970s in China. Summarizing the clinical evidence of ATO in cancer is conducive to further understanding, development, and promotion of its pharmacological research.
It is the first time to comprehensively assess and summarize the evidence of ATO in cancer treatment via umbrella review.
8 databases in English or Chinese from their inception to February 21, 2023 were searched by two reviewers separately and suitable meta-analyses (MAs) were included in this umbrella review. Their methodological quality and risk of bias were evaluated and data of outcomes was extracted and pooled again. The evidence certainty of pooled results was classified.
17 MAs with 27 outcomes and seven comparisons in three cancers were included in this umbrella review. However, their methodological quality was unsatisfactory with 6 MAs as low quality and 12 MAs as critically low quality. Their shortcomings were mainly focused on protocol, literature selecting, bias risk, small sample study bias, and conflicts of interest or funding. And they were all assessed as high risk in bias. It was suggested that ATO had an advantage in enhancing complete remission rate, event-free survival, and recurrence free survival and decreasing recurrence rate, cutaneous toxicity, hyper leukocyte syndrome, tretinoin syndrome, edema and hepatotoxicity in different comparisons of APL with low or moderate certainty. Besides, compared with transcatheter arterial chemoembolization (TACE) alone, ATO plus TACE also could improve objective response rate, disease control rate, survival rate (0.5, 1, 2, and 3-year) and life quality and reduce the level of alpha fetoprotein in primarily hepatocellular carcinoma with low or moderate certainty. However, no significant results were found in MM. Finally, key findings were as followed. ATO has potential broad-spectrum anticancer effects but the clinical transformation is rarely achieved. Route of administration may affect the antitumor effects of ATO. ATO can act synergistically in combination with a variety of antitumor therapies. The safety and drug resistance of ATO should be paid more attention to.
ATO may be a promising drug in anticancer treatment although earlier RCTs have dragged down the level of evidence. However, high-quality clinical trials are expected to explore its broad-spectrum anticancer effects, wide application, appropriate route of administration, and compound dosage form.
三氧化二砷（ATO）作为一种天然矿物药物，在中国已有 2000 多年的历史，用于治疗疾病。自 20 世纪 70 年代以来，ATO 已应用于治疗急性早幼粒细胞白血病（APL）。总结 ATO 在癌症治疗中的临床证据有助于进一步了解、开发和推广其药理学研究。
这是首次通过伞式综述全面评估和总结 ATO 在癌症治疗中的证据。
两位评审员分别从英语或中文 8 个数据库中检索，检索时间从数据库建立到 2023 年 2 月 21 日，纳入了适合的荟萃分析（MA）。对其方法学质量和偏倚风险进行评估，并再次提取和汇总结局数据。对汇总结果的证据确定性进行分类。
本伞式综述纳入了 17 项 MA，共涉及三种癌症中的 27 个结局和 7 个比较。然而，其方法学质量并不令人满意，6 项 MA 质量较低，12 项 MA 质量极低。它们的缺陷主要集中在方案、文献选择、偏倚风险、小样本研究偏倚、利益冲突或资金方面。并且它们都被评估为高偏倚风险。结果表明，ATO 在提高完全缓解率、无事件生存率和无复发生存率以及降低复发率、皮肤毒性、高白细胞综合征、维甲酸综合征、水肿和肝毒性方面具有优势，在不同比较中具有中到低确定性。此外，与单独经导管动脉化疗栓塞（TACE）相比，ATO 加 TACE 也能提高原发性肝癌的客观缓解率、疾病控制率、生存率（0.5、1、2 和 3 年）和生活质量，并降低中到低确定性的甲胎蛋白水平。然而，在多发性骨髓瘤（MM）中没有发现显著结果。最后，关键发现如下。ATO 具有潜在的广谱抗癌作用，但临床转化很少实现。给药途径可能会影响 ATO 的抗肿瘤作用。ATO 可以与多种抗肿瘤疗法协同作用。应更加注意 ATO 的安全性和耐药性。
尽管早期的 RCT 降低了证据水平，但 ATO 可能是一种有前途的抗癌药物。然而，需要高质量的临床试验来探索其广谱抗癌作用、广泛应用、合适的给药途径和复合剂型。
