Chen, M., Zhang, L., Wang, Q., & Shen, J. (2013). Pyridoxine for prevention of hand-foot syndrome caused by chemotherapy: A systematic review. PloS One, 8(8), e72245.

DOI Link

Purpose

STUDY PURPOSE: To evaluate the evidence related to the efficacy of pyridoxine (vitamin B6) in preventing hand-foot syndrome (HFS) caused by anti-cancer therapies

TYPE OF STUDY: Systematic review

Search Strategy

DATABASES USED: Cochrane Central Register of Controlled Trials (CENTRAL) in Cochrane Library, PUBMED, EMBASE, LILACS, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals, WANFANG, and the U.S. ClinicalTrials.gov website
 
KEYWORDS: Pyridoxine*, vitamin B6, hand foot syndrome*, and palmar-plantar erythrodysesthesia
 
INCLUSION CRITERIA: Adult patients > 18 years old receiving anti-cancer chemotherapies with an Eastern Cooperative Oncology Group performance status of 0–2, a life expectancy > 12 weeks, and no contraindication to chemotherapy (e.g., bone marrow is functioning adequately and kidney and liver function is normal). Included all randomized controlled trials (RCTs) in all languages. 
 
EXCLUSION CRITERIA: Previous treatment for HFS, hypersensitivity to pyridoxine, pregnancy, lactation, or studies that enrolled a combination of drug use for HFS

Literature Evaluated

TOTAL REFERENCES RETRIEVED: N = 270
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Reviewers from different professions reviewed all potential studies independently and extracted data. Subgroup analysis was planned according to the dose of pyridoxine. Risk of bias was independently assessed by three authors using a standard form. To measure the effectiveness of the pyridoxine in preventing HFS, a risk ratio (RR) with a 95% confidence interval (CI) was calculated for the meta-analysis. The Review Manager version 5.1.0 software was used to perform the meta-analysis.  

Sample Characteristics

FINAL NUMBER STUDIES INCLUDED: 5
 
TOTAL PATIENTS INCLUDED IN REVIEW: 612 patients 
 
KEY SAMPLE CHARACTERISTICS: Mean age was 62.1 years (range 20–87). There was a wide range of cancer types including colorectal, breast, ovarian, stomach biliary tract, endometrial, and duodenum. Colorectal cancer patients were most commonly represented in this study (350 patients). The capecitabine dose was initiated at 2000–2500 mg/m2 orally per day, either alone or as part of a combination treatment, for two weeks and was followed by seven days rest. The pegylated liposomal doxorubicin (PLD) dose was 40 mg/m2 intravenously every four weeks for single-agent therapy. The oral pyridoxine was prescribed to begin on the same day that the chemotherapy regimen started. Chemotherapy treatment continued until the patient experienced disease progression or toxicity, or if the patient preferred to stop the treatment. Five patients were excluded because of reactions to the chemotherapy during the first course of chemotherapy. The remaining 607 patients were part of the meta-analysis.     

Phase of Care and Clinical Applications

PHASE OF CARE:  Active antitumor treatment
 
APPLICATIONS: Elder care

Results

  • Incidence of HFS: No statistically significant differences were found in the risk of HFS among patients receiving placebo compared to pyridoxine (RR 0.96; 95% CI, 0.86–1.06; n = 551).  
  • Incidence of grade 2 or worse HFS: No statistically significant differences were found in the risk of grade 2–4 HFS among patients receiving a placebo compared to pyridoxine (RR 0.96; 95% CI, 0.73–1.24; n = 551). In regard to different doses of pyridoxine, significant differences were found for prevention of grade 2 or grade 3 HFS with pyridoxine 400 mg PO daily compared to 200 mg PO. (RR 0.55; 95% CI, 0.33–0.92; n = 56).  
  • Time to development of grade 2 or worse HFS: The median time for development of grade 2 or worse HFS was reported in one trial. Although the pyridoxine 400 mg group (87 days) was slightly longer than the 200 mg group (61 days), no statistical significant difference was found (p = 0.44).  
  • Quality of life (QOL): In 2 RCTs (n = 106 and n = 34), there were no significant differences in QOL between the pyridoxine group and the placebo groups.  

Conclusions

Based on the analysis of results of five randomized controlled trials, there is not sufficient evidence to make any recommendation for patients taking pyridoxine to prevent HFS caused by chemotherapy drugs. However, that data suggests that pyridoxine 400 mg was more effective in preventing grade 2 and grade 3 HFS than pyridoxine 200 mg. Future research studies that include large sample sizes are needed to continue to evaluate pyridoxine’s efficacy and safety, especially high doses of pyridoxine, in comparison with placebo.

Limitations

  • Information from primary studies was not sufficient to perform subgroup analysis by types of chemo regimen.  
  • This review included only RCTs.  
  • Adverse effects of pyridoxine were not assessed absolutely.

Nursing Implications

HFS is a relatively common skin toxic reaction to certain chemotherapy. Nurses may collaborate with physicians in identifying effective treatments. Although RCT results do not support using pyridoxine for preventing HFS caused by chemotherapy, pyridoxine 400 mg PO may have some efficacy in preventing grade 2 and 3 HFS.

Legacy ID

4436