| Objective:1. To evaluate the clinical efficacy and safety of traditional Chinese medicine (TCM) for preventing Oxaliplatin-induced peripheral neurotoxicity by evidence-based medicine (EBM), thus providing relatively reliable evidence for clinical practice.2. To analysis the application guideline of TCM for preventing Oxaliplatin-induced peripheral neurotoxicity.3. To discuss the drawbacks of current clinical researches towards TCM prevention of Oxaliplatin-induced peripheral neurotoxicity and provide methodological guideline for TCM clinical studies.Methods:CBM, CNKI, VIP, Wan Fang Database, Medline, EMBASE, and CENTRAL were searched from inception through to October 2015 for clinical randomized controlled trials (RCTs) for prevention of Oxaliplatin-induced peripheral neurotoxicity by TCM, supplemented by manual retrieval. Repetitive searches and repetitive published literatures were eliminated, screening literatures by inclusion criteria and exclusion criteria, then extract data from the included trials. The methodological quality of eligible studies was evaluated using the Cochrane Risk Bias Assessment tool (Version 5.1.0) released by the Cochrane Collaboration, and summarized effects were calculated using Reviewer Manager 5.3 software.Results:1.75 publications in total were included. The methodological quality of all the included trials was low. The main issues were as follows:nonstandard randomization, missing concealed allocation, missing blind method and impropriety in handling losses of participants.2. Traditional Chinese Compound Prescriptions were used in the 65 included literatures. The following categories of TCM had the higher frequency:the TCM with the function of promoting blood circulation and dredging collaterals (126 times), the TCM with the function of tonifying Qi (120 times), the TCM with the function of nourishing blood (73 times), the TCM with the function of warming-promoting (58 times). The following 3 herb medicine had the highest frequency:Astragalus mongholicus (42 times), Angelica sinensis (30 times), Cassia Twig (30 times). TCM injections were used in the 10 included literatures, which were considered to have the function of tonifying Qi and activating blood circulation.3. Total incidence of peripheral neurotoxicity:3.1 "chemotherapy+TCM" vs "chemotherapy alone or chemotherapy+placebo":Included 59 trials and 3845 patients. Summary analysis illustrated:RR=0.60,95%CI:[0.56,0.64],P<0.00001. Subgroup analysis:TCM orally, RR=0.58,95%CI:[0.53,0.64], P<0.00001; external application of TCM, RR=0.62,95%CI:[0.57,0.67], P<0.00001; TCM injections, RR=0.57,95%CI: [0.48,0.69], P<0.00001; test of subgroup differences showed P=0.57. All the results had low sensitivity, good stability and no obvious publication bias.3.2 "chemotherapy+TCM" vs "chemotherapy+conventional western medicine":Included 5 trials and 444 patients. Meta-analysis illustrated:RR=0.50,95%CI:[0.41,0.62], P<0.00001. The result had low sensitivity, good stability and no obvious publication bias.3.3 "chemotherapy+TCM+conventional western medicine" vs "chemotherapy+conventional western medicine":Included 7 trials and 472 patients. Meta-analysis elucidated:RR=0.42, 95%CI:[0.32,0.54], P<0.00001. The result had low sensitivity, good stability and no obvious publication bias.4.1ncidence of severe peripheral neurotoxicity:4.1 "chemotherapy+TCM" vs "chemotherapy alone or chemotherapy+placebo":Included 59 trials and 3818 patients. Meta-analysis illustrated:RR=0.34,95%CI:[0.28,0.43], P<0.00001. The result had low sensitivity, good stability and no obvious publication bias.4.2 "chemotherapy+TCM" vs "chemotherapy+conventional western medicine":Included 6 trials and 504 patients. Meta-analysis illustrated:RR=0.51,95%CI:[0.19,1.34], P=0.17, there was no significant difference statistically between treatment group and control group. The result had low sensitivity, good stability and no obvious publication bias.4.3 "chemotherapy+TCM+conventional western medicine" vs "chemotherapy+conventional western medicine":Included 8 trials and 32 patients. Meta-analysis illustrated:RR=0.32, 95%CI:[0.14,0.75], P=0.008. The result had low sensitivity, good stability and no obvious publication bias.5. The incidence of severe leucopenia:Included 24 trials and 1604 patients. Meta-analysis illustrated:RR=0.46,95%CI:[0.32,0.65], P<0.00001.6. The incidence of severe thrombocytopenia:Included 21 trials and 1445 patients. Meta-analysis illustrated:RR=0.66,95%CI:[0.38,1.17], P=0.15. There was no significant difference statistically between treatment group and control group.7. The incidence of severe gastrointestinal reaction:Included 24 trials and 1485 patients. Meta-analysis illustrated:RR=0.63,95%CI:[0.46,0.87], P=0.005.8. The incidence of severe hypohepatia:Included 22 trials and 1493 patients. Meta-analysis illustrated:RR=0.50,95%CI:[0.26,0.97], P=0.04.9. The incidence of severe renal damage:Included 17 trials and 1267 patients. Meta-analysis illustrated:RR=0.46,95%CI:[0.11,2.00], P=0.30. There was no significant difference statistically between treatment group and control group.10. The incidence of other adverse events:There were 6 trials (9 patients) with external washing of TCM. One patient had scald. Eight patients had mild skin irritation. Meta analysis illustrated: there was no significant difference statistically between treatment group and control group (P=0.05).Conclusion:1. For preventing Oxaliplatin-induced peripheral neurotoxicity with Traditional Chinese Medicines, TCM prescriptions and injections with the functions of invigorating Qi and nourishing blood, activating blood, warming and activating meridian shall be utilized.2. Whether oral or external administration or intravenous injection of TCM can effectively prevent the incidence of Oxaliplatin-induced peripheral neurotoxicity. TCM is also able to effectively decrease the incidence of Oxaliplatin-induced severe peripheral neurotoxicity.3. Compared with conventional western medicine treatment, TCM has a better efficiency in preventing the incidence of Oxaliplatin-induced peripheral neurotoxicity. Nevertheless, more evidences are needed to support that this efficacy of TCM is better than conventional western medicine.4. TCM can enhance the therapeutic effect of conventional western medicine to prevent the incidence of Oxaliplatin-induced peripheral neurotoxicity severe peripheral neurotoxicity.5. TCM has a good safety profile in preventing the incidence of Oxaliplatin-induced peripheral neu-rotoxicity. TCM can reduce the incidence of severe leucopenia, severe gastrointestinal reaction and severe hypohepatia. No other adverse events are observed.6. At present, the clinical RCTs of TCM generally have the low methodological quality.7. The above conclusion shall be further confirmed by more multi-center, large sample and standardized clinical RCTs, due to the limited quantity and quality of the included studies, as well as the limitations of this systematic review. |
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