Deng, B., Jia, L., & Cheng, Z. (2016). Radix Astragali-based Chinese herbal medicine for oxaliplatin-induced peripheral neuropathy: A systematic review and meta-analysis. Evidence-Based Complementary and Alternative Medicine, 2016, 2421876. 

DOI Link

Purpose

STUDY PURPOSE: To conduct a systematic review of the research evidence for the effects of Radix Astragali (RA)–based Chinese herbal medicine in the prevention and treatment of oxaliplatin-induced peripheral neuropathy (PN)

TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy

DATABASES USED: MEDLINE (1982–2015), Cochrane Controlled Trials (2015, Issue 12), Springer (1997–2015), China National Knowledge Infrastructure (CNKI) (1997–2015), Wangfang Database of China Science Periodical Database (CSPD) (1998–2015)
 
INCLUSION CRITERIA: All randomized, controlled trials (RCTs) examining the use of RA-based Chinese herbal medicine (single or a compound of several herbs, all dose forms [i.e., oral, decoction, or lotion] and deliveries [i.e., oral, topical, or intravenous]) for its effects on preventing and treating oxaliplatin-induced PN; adults aged 18 years or older with confirmed malignant pathology or cytology treated with OXAL, FOLFOX, or XELOX 
 
EXCLUSION CRITERIA: RCTs with unclear diagnostic confirmation; RCTs without the use of RA, other herbal combinations, or other forms of complementary alternative therapy; animal studies

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 841
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Medline = 1, Springer = 1, Cochrane = 0, CNKI = 475, Wangfang = 364 studies. Data were extracted independently by two authors using an electronic database. Quality of RCTs was evaluated with the improved Jadad scale (high quality score 4–7) and guided by the Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0. Eight hundred forty-one studies were screened for title and abstract review, 731 were excluded, and 110 studies evaluated by full-text review. Final studies were based on eligibility in this systematic review (n = 24). All studies included were from mainland China (4 RCTs from 2009 and 20 RCTs from 2011–2015). Data synthesis employed Review Manager (RevMan), 5.0, to analyze the results of RCTs. Dichotomous data were reported as odds ratio, and continuous data were reported as mean difference. In the meta-analysis, heterogeneity was evaluated between RCTs results and considered significant if more than 50% (p < 0.1). If significant heterogeneity was found between the RCT results, a random effect model was used in the meta-analysis; otherwise, a fixed effect model was used if no significant heterogeneity existed. A funnel plot analysis was used to evaluate publication bias.

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 24 
  • TOTAL PATIENTS INCLUDED IN REVIEW = 1,552
  • SAMPLE RANGE ACROSS STUDIES: 40–135; average size = 66
  • KEY SAMPLE CHARACTERISTICS: 11 trials inpatients (n = 689); no setting identified for the other 13 trials (n = 863); 24 trials = 58.63% were male; colorectal cancer (n = 1,033); gastric cancer (n = 399); lung/breast/other cancers (n = 52), not specified (n = 68); range for total OXALI dose in all studies = 130 mg/m2–800 mg/m2; range for total OXALI dose in 11 trials 260–600 mg/m2

Phase of Care and Clinical Applications

PHASE OF CARE: Not specified or not applicable; cannot determine if studies were in palliative care setting

APPLICATIONS: Elder care

Results

The findings showed significant results in these areas: reduced chemotherapy-induced peripheral neuropathy (CIPN) all-grade incidence, reduced high-grade incidence, and improved sensory nerve conduction velocity
  • Fifteen RCTs comparing RA-based combined remedies to no intervention significantly reduced CIPN occurrence (n = 993 patients, odds ratio [OR] = 0.19, 95% CI confidence interval [0.14, 0.25], p < 0.01).
  • One RCT comparing RA-based prescription to mecobalamin reduced CIPN occurrence (n = 42 patients, OR = 0.17, 95% CI [0.03, 0.94], p < 0.05).
  • Two RCTs comparing RA-based prescription in addition to reduced glutathione versus calcium/magnesium infusions with the same conventional medications reduced CIPN occurrence (n = 120 patients, OR = 0.42, 95% CI [0.18, 0.97], p < 0.05).
  • Fourteen RCTs comparing RA-based intervention versus no intervention significantly reduced the incidence of high-grade PN (11 trials used Levi’s grading) (n = 931 patients, OR = 0.17, 95% CI [0.09, 0.31], p < 0.01). No significant difference was found in the two trials comparing RA to mecobalamin or the two trials comparing RA to reduced glutathione or calcium/magnesium infusion with the same conventional medications. 
  • Three RCTs comparing RA-based prescriptions and mecobalamin to mecobalamin alone found significant effect for RA-based prescription and mecobalamin in relieving CIPN (n = 213 patients, OR = 4.84, 95% CI [2.38, 9.83], p < 0.01).
  • Six RCTs reported that the TA-based intervention significantly improved sensory nerve conduction velocity (MD = 4.42 m/s, 95% CI [3.27, 5.57], p < 0.01). No difference existed in motor nerve conduction velocity.
  • No adverse events were reported in the 24 included studies for RA-based interventions. No consistent data was reported for quality of life, with only two trials including quality of life improvement after RA-based interventions.
  • Funnel plots did not indicate publication bias.
  • Effect sizes were not reported.

Conclusions

This meta-analysis indicated that RA-based interventions may provide potential benefit for oxaliplatin-induced PN. Although this meta-analysis did not show significant heterogeneity for different trial results, it did show considerable heterogeneity in the variables, treatments, and outcome measures studied. Studies included RA-based interventions with no reliable measures of drug composition, varied drug doses, self-made drug preparations, or RA combined with herbal compositions with variation in drug delivery methods. Therefore, it is premature to interpret these results as beneficial because of the substantial limitations for reliability and validity of the study results.

Limitations

  • Limited search
  • High heterogeneity
  • Low sample sizes
  • Predominant yield of studies from only two databases: CNKI and Wanfang
  • Safety, adverse event, or quality of life not used in search terms
  • Twenty-four RCTs included three different CIPN grading scales.
  • More than 50% of RA-based prescriptions included other herbal substances.
  • No consistent reliable measure of drug composition
  • Ten of the 24 RCTs had self-made prescriptions.
  • Different RCT comparators (i.e., intervention, no intervention)
  • More RCTs comparing RA-based prescription versus no intervention
  • Doses/administration/duration of RA treatment different (oral = 10 RCTs, topical = 12 RCTs, IV = 1 RCT)
  • Unclear phase of care or previous neurotoxic chemotherapy exposures
  • Differences in duration of chemotherapy exposures and accumulated OXALI doses
  • No multicenter large scale trials
  • Effect sizes were not reported.

Nursing Implications

It remains unclear if RA provides benefit in alleviating oxaliplatin-induced PN. Additional RCTs are required to evaluate the reliable preparations of RA to investigate its full effects isolated in simple form versus its combined effect with other herbs. The effect of RA on the antitumor activity of oxaliplatin or other chemotherapeutic agents needs further study. Large multisite RCTs are needed to further evaluate drug safety in all phases of treatment and to identify the most effective dose, delivery method, duration of treatment, and quality of life.

Legacy ID

6503