Aidi injection plus platinum-based chemotherapy for stage IIIB/IV non-small cell lung cancer: A meta-analysis of 42 RCTs following the PRISMA guidelines

Abstract

Ethnopharmacological relevance: Aidi injection is one of the most commonly used Chinese patent medicines for advanced non-small cell lung cancer (NSCLC). It is made from an extraction of Mylabris Phalerata, Radix Astragalus, Radix Ginseng, and Acanthopanax Senticosus.

Aim of the study: The objective of this study is to evaluate the efficacy and safety of Aidi injection in combination with platinum-based chemotherapy for stage IIIB/IV NSCLC.

Materials and methods: A systematic review and meta-analysis were performed following the PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Trials were combined using Review Manager 5.3 and Comprehensive Meta-Analysis(CMA) 2.0. Dichotomous data were expressed as risk ratio (RR) and continuous outcomes as weighted mean difference (WMD), with their 95% confidence intervals (CI) respectively. All randomized controlled trials (RCTs) comparing Aidi injection plus platinum-based chemotherapy versus platinum-based chemotherapy, with efficacy and safety outcomes were selected. Disease Control Rate (DCR) was the primary outcome, Objective Response Rate (ORR), survival rate, quality of life (QOL), and toxic effects were the secondary outcomes.

Results: 42 RCTs recruiting 4081 patients with stage IIIB/IV NSCLC were included, with overall low-moderate methodological quality. Compared with platinum-based chemotherapy alone, Aidi injection plus platinum-based chemotherapy can increase relative benefit of DCR (RR = 1.13, 95% CI 1.09-1.16, P < 0.00001), ORR (RR = 1.26, 95% CI 1.18-1.36, P < 0.00001), improve 1-, 2-, 3-year survival rates (RR = 1.14, 95% CI 1.02-1.28, P = 0.03; RR = 1.31, 95% CI 1.05-1.64, P = 0.02; and RR = 1.88, 95% CI 1.32-2.67, P = 0.0005, respectively), QOL (RR = 1.80, 95% CI 1.61-2.01, P < 0.00001), and reduce severe (grade 3 and 4) toxicities by 36% (RR = 0.64, 95% CI 0.58-0.70, P < 0.00001).

Conclusions: From the available evidence, compared with platinum-based chemotherapy alone, Aidi injection plus platinum-based chemotherapy improves the clinical efficacy and alleviates the toxicity of chemotherapy in patients with stage IIIB/IV NSCLC. However, considering the intrinsic limitations of the included RCTs, well-designed, rigorously performed, high-quality trials are still required to further assess and confirm the results.

Keywords: Aidi injection; Astragaloside II (PubChem CID: 71306915); Astragaloside IV (PubChem CID: 13943297); Cantharidin (PubChem CID: 5944); Chemotherapy; Efficacy; Ginsenoside Rb1 (PubChem CID: 118987129); Ginsenoside Rc (PubChem CID: 12855889); Ginsenoside Rd (PubChem CID: 24721561); Ginsenoside Re (PubChem CID: 441921); Ginsenoside Rg1 (PubChem CID: 441923); Ginsenoside Rg3 (PubChem CID: 9918693); Ginsenoside Rh2 (PubChem CID: 119307); Isofraxidin (PubChem CID: 5318565); Meta-analysis; NSCLC; Safety; Stage IIIB/IV; Syringin (PubChem CID: 5316860); Systematic review; Toxicity; Trial Sequential Analysis.