Efficacy of Traditional Chinese Medicine Injection in Preventing Oxaliplatin-Induced Peripheral Neurotoxicity: An Analysis of Evidence from 3598 Patients

Abstract

Background: Oxaliplatin is an effective chemotherapeutic agent for the treatment of malignant tumors. However, severe oxaliplatin-induced peripheral neurotoxicity (OIPN) has been well documented. Traditional Chinese medicine injections (TCMIs) have shown significant efficacy in preventing OIPN. However, it is difficult for clinicians to determine the differences in the efficacy of various TCMIs in preventing OIPN. The aim of this study was to compare the efficacy of various TCMIs in preventing OIPN through a network meta-analysis (NMA) to further inform clinical decision-making.

Methods: The Chinese Journal Full Text Database, Chinese Biomedical Literature Database, Wanfang Data Knowledge Service Platform, Chinese Science and Technology Journal Full Text Database, the Cochrane Library, Web of Science, PubMed, and Embase databases were searched for randomized controlled trials (RCTs) of TCMIs for OIPN prevention. The retrieval time was from the establishment of the database to April 12, 2021. NMA was performed using Stata 14.0 software after 2 evaluators independently screened the literature, extracted information, and evaluated the risk of bias of the included studies.

Results: A total of 45 eligible RCTs involving 3598 cancer patients and 13 TCMIs were included. The 13 TCMIs included Xiaoaiping injection (XAPI), compound kushen injection (CKSI), Aidi injection (ADI), Brucea javanica oil emulsion injection (BJOEI), Shenmai injection (SMI), Kangai injection (KAI), Astragalus injection (AI), elemene emulsion injection (EEI), Shenfu injection (SFI), Shenqi Fuzheng injection (SIFZI), Kanglaite injection (KLEI), Huachansu injection (HCSI), and lentinan injection (LI). NMA results showed that AI was superior to AD and SIFZI was superior to ADI in reducing the incidence of grade I neurotoxicity. SIFZI was superior to EEI and ADI, and BJOEI was superior to chemotherapy alone in reducing the incidence of grade II neurotoxicity. SMI was superior to LI and CKSI in reducing the incidence of grade III neurotoxicity. SIFZI was superior to LI, BJOEI, XAPI, EEI, SMI, chemotherapy alone, HCSI, KLEI, and ADI in reducing the total incidence of grade I-IV neurotoxicity. SFI was superior to ADI. Based on the SUCRA values, AI was the most likely intervention to reduce the incidence of grade I neurotoxicity, SIFZI was the most likely intervention to reduce the total incidence of grade II and I-IV neurotoxicity, and SMI was the most likely intervention to reduce the incidence of grade III and IV neurotoxicity.

Conclusion: TCMIs can prevent OIPN to some extent, among which SIFZI, SMI, and AI may be the most promising TCMIs. However, given the limitations of current studies, more well-designed, high-quality clinical trials will be needed in the future to validate the benefits of TCMIs.

Figure 1

Flowchart of the literature screening process.

Figure 2

Risk of bias graph of the included RCTs. (a) Risk of bias summary; (b) risk of bias graph.

Figure 3

Network diagrams for different outcomes. (a) Incidence of grade I neurotoxicity; (b) incidence of grade II neurotoxicity; (c) incidence of grade III neurotoxicity; (d) incidence of grade IV neurotoxicity; (e) total incidence of grade I ∼ IV neurotoxicity.

Figure 4

Pooled estimates of the network meta-analysis. (a) Pooled relative risk (95% confidence intervals) for the incidence of grade I neurotoxicity; (b) pooled relative risk (95% confidence intervals) for the incidence of grade II neurotoxicity; (c) pooled relative risk (95% confidence intervals) for the incidence of grade III neurotoxicity; (d) pooled relative risk (95% confidence intervals) for the incidence of grade IV neurotoxicity; (e) pooled relative risk (95% confidence intervals) for the total incidence of grade I ∼ IV neurotoxicity.

Figure 5

The surface under the cumulative ranking curve (SUCRA) plots for different outcomes. (a) Incidence of grade I neurotoxicity; (b) incidence of grade II neurotoxicity; (c) incidence of grade III neurotoxicity; (d) incidence of grade IV neurotoxicity; (e) total incidence of grade I ∼ IV neurotoxicity.

Figure 6

Publication bias. (a) Incidence of grade I neurotoxicity comparison-correction funnel chart; (b) incidence of grade II neurotoxicity comparison-correction funnel chart; (c) incidence of grade III neurotoxicity comparison-correction funnel chart; (d) total incidence of grade I ∼ IV neurotoxicity comparison-correction funnel chart.