■结直肠癌(CRC)是常见的恶性肿瘤之一,发病率逐渐增加。由于检测晚,对化疗敏感性差,目前已成为肿瘤防治的一大难题。探索或发现新的组合是治疗CRC的重要策略。复方苦参注射液(CKI)是从苦参中提取的中药注射剂。和SmilaxglabraRoxb.,在我国CRC的综合治疗中应用广泛。本系统综述旨在根据现有数据确定CKI联合化疗治疗晚期CRC的临床疗效和安全性。在此基础上,进一步讨论了CKI联合化疗在临床实践中的具体应用。
■PubMed,WebofScience,Cochrane图书馆,EMBASE,中国国家知识基础设施,中国科技期刊数据库,万方数据库,中国生物医学数据库检索,中国临床试验注册中心,和ClinicalTrials.gov进行了系统的搜索,从成立到2024年4月20日。我们采用了ROB2工具来评估纳入试验的质量,Stata16用于数据分析,并用漏斗图和Egger检验对发表偏倚进行了评估。根据等级,证据的质量是合理的。我们还使用试验序贯分析(TSA)来计算此荟萃分析中的最终所需样本量,并验证结果是否提供可靠的结论。本系统评价的方案已在PROSPERO(CRD42022380106)上注册,并已发布。
■这项研究包括了16项检查1378名患者的试验。Meta分析显示,与化疗相比,客观反应率(ORR,RR=1.30,95%CI:1.18-1.44),疾病控制率(DCR,RR=1.08,95%CI:1.03-1.13),CKI联合化疗可提高晚期CRC患者KPS评分改善率(RR=1.18,95%CI:1.07~1.31)。此外,CKI联合化疗可降低白细胞减少等不良反应(RR=0.74,95%CI:0.62-0.87),血小板减少症(RR=0.68,95%CI:0.49-0.94),胃肠道反应(RR=0.72,95%CI:0.55-0.94),和肝损伤(RR=0.48,95%CI:0.30-0.79),更高的CD4+比率(MD=9.70,95%CI:8.73-10.68)和CD4+/CD8+比率(MD=0.25,95%CI:0.22-0.28),和较低的CD8+T细胞比率(MD=-5.25,95%CI:-5.94至-4.56)。亚组分析表明,CKI联合FOLFOX和5Fu+L-OHP治疗晚期CRC患者的ORR和DCR均有改善。15和20ml/天的CKI与FOLFOX的组合在ORR中提供了显著的效果。此外,当累积的CKI剂量达到每个疗程280ml和总计420ml时,ORR得到改善。7天/疗程以及14天/疗程的CKI联合FOLFOX是ORR的有效持续时间。至于DCR,7天/疗程的CKI联合FOLFOX可以提高疗效。此外,CKI+FOLFOX可用于ORR和DCR至少4个周期的联合治疗。TSA表明,ORR和DCR的可靠结果已经建立,其他试验不太可能改变结果。
■CKI联合化疗在改善ORR方面具有统计学意义和临床重要作用,DCR,性能状态,ADR减少,结直肠癌患者的免疫功能。然而,更严格的设计,大规模,未来需要多中心RCT。
UNASSIGNED: Colorectal cancer (CRC) is one of the common malignant tumors, with a gradually increasing incidence. Due to late detection and poor sensitivity to chemotherapy, it has become a difficult problem in tumor prevention and treatment at present. Exploring or discovering new combinations is a significant strategy for the treatment of CRC. Compound kushen injection (CKI) is a traditional Chinese medicine injection extracted from
Sophora flavescens Ait. and Smilax glabra Roxb., which is widely used in the comprehensive treatment of CRC in China. This systematic review is aimed to ascertain the clinical efficacy and safety of CKI combined with chemotherapy in the treatment of advanced CRC based on available data. On this basis, the specific application of CKI in combination with chemotherapy in clinical practice is further discussed.
UNASSIGNED: PubMed, Web of Science, the Cochrane Library, EMBASE, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang Database, Chinese Biomedicine Database Searches, the Chinese Clinical Trial Registry, and ClinicalTrials.gov were searched systematically, from inception to April 20, 2024. We adopted the ROB2 tool to assess quality of the included trials, Stata 16 for data analysis, and evaluated the publication bias with the funnel plot and Egger\'s test. The quality of the evidence was justified according to GRADE. We also used trial sequential analysis (TSA) to calculate the final required sample size in this meta-analysis and to verify whether the results present a reliable conclusion. The protocol for this systematic review was registered on PROSPERO (CRD42022380106) and has been published.
UNASSIGNED: Sixteen trials that examined 1378 patients were included in this study. Meta-analysis revealed that compared with chemotherapy, objective response rate (ORR, RR = 1.30, 95% CI: 1.18-1.44), disease control rate (DCR, RR = 1.08, 95% CI: 1.03-1.13), and KPS score improvement rate were improved (RR = 1.18, 95% CI: 1.07-1.31) by the combination of CKI and chemotherapy in patients with advanced CRC. Additionally, CKI combined with chemotherapy was associated with lower adverse reactions such as leukopenia (RR = 0.74, 95% CI: 0.62-0.87), thrombocytopenia (RR = 0.68, 95% CI: 0.49-0.94), gastrointestinal reactions (RR = 0.72, 95% CI: 0.55-0.94), and liver damage (RR = 0.48, 95% CI: 0.30-0.79), higher CD4+ ratio (MD = 9.70, 95% CI:8.73-10.68) and CD4+/CD8+ ratio (MD = 0.25, 95% CI: 0.22-0.28), and lower CD8+ T cell ratio (MD = -5.25, 95% CI: -5.94 to -4.56). Subgroup analysis demonstrated that ORR and DCR in patients with advanced CRC were improved when CKI combined with FOLFOX and 5Fu + L-OHP. Both 15 and 20 ml/day of CKI combined with FOLFOX provided a significant effect in ORR. Moreover, ORR was improved when the accumulated CKI dose reached 280 ml per course and 420 ml in total. 7 days/course as well as 14 days/course of CKI combined with FOLFOX were effective durations in ORR. As for DCR, 7 days/course of CKI combined with FOLFOX could improve efficacy. Furthermore, CKI + FOLFOX may be useful in ORR and DCR for at least 4 cycles of combination therapies. The TSA showed that firm results in ORR and DCR were established and additional trials were unlikely to change the results.
UNASSIGNED: CKI combined with chemotherapy provides a statistically significant and clinically important effect in the improvement of ORR, DCR, performance status, ADR reduction, and immune function in patients with CRC. However, more rigorously designed, large-scale, and multi-center RCTs are needed in the future.