Pyridoxine for prevention of hand-foot syndrome caused by chemotherapy: a systematic review

Abstract

Background: Hand-foot syndrome (HFS) is a relatively frequent dermatologic toxic reaction to certain anti-cancer chemotherapies. The syndrome can evolve into a distressing condition that limits function and affects quality of life. Pyridoxine (vitamin B6) has been used empirically for the prevention of HFS caused by anti-cancer therapy. However, evidence of its efficacy remains controversial.

Methodology//principal findings: Systematic literature searches were conducted on the Cochrane Library, PUBMED, EMBASE, LILACS, CBM, CNKI, VIP, WANFANG and the U.S. ClinicalTrials.gov website. We included all related randomized controlled trials (RCTs) irrespective of language. Reviewers from different professions independently assessed all potential studies and extracted data. Subgroup analysis was planned according to dose of pyridoxine. 5 RCTs involving 607 patients were contributed to the meta-analysis. No significant differences were found between patients receiving pyridoxine and placebo for prevention of incidence of HFS and grade 2 or worse HFS (relative risk (RR) 0.96, 95%confidence interval (CI) 0.86-1.06; RR0.95, 95%CI 0.73-1.24, respectively). Similarly, no significant improvement in quality of life was detected among patients. However, significant difference was found for prevention of grade 2 or worse HFS with pyridoxine 400 mg daily compared to 200 mg (RR0.55, 95%CI 0.33-0.92).

Conclusions/significance: There is inadequate evidence to make any recommendation about using pyridoxine for prevention of HFS caused by chemotherapy. However, pyridoxine 400 mg may have some efficacy. Further studies of large sample sizes are needed to evaluate the efficacy and safety of pyridoxine, especially at high dose, in comparison with placebo.

Figure 1. Flow diagram of study selection process.

This PRISMA 2009 flow diagram illustrates the results of search and the process of screening and selecting studies for inclusion, and the reasons for exclusions in this review.

Figure 2. Quality assessment in included studies.

This plot is created by the software of RevMan 5.1.0. It illustrates the quality of included studies with each of the judgement (‘low risk’, ‘high risk’ or ‘unclear risk’ of bias). All studies had low risk bias in selective reporting and other issues, and unclear risk in random sequence generation. One study (Fang 2010) had high risk bias in allocation concealment and blinding.

Figure 3. Forest plot showing the meta-analysis of pyridoxine versus placebo in the incidence of Hand-foot syndrome.

This forest plot is created by the software of RevMan 5.1.0. Horizontal lines indicate 95% CIs. Solid boxes indicate the response rate in each study. Test of heterogeneity (I² = 0%) indicates the absence of substantial heterogeneity. The bottom of diamond indicates the pooled response rate (RR0.96, P = 0.99).

Figure 4. Forest plot showing the meta-analysis of pyridoxine versus placebo in the incidence of grade 2 or worse Hand-foot syndrome.

This forest plot is created by the software of RevMan 5.1.0. Test of heterogeneity (I² = 0%) indicates the absence of substantial heterogeneity. The bottom of diamond indicates the pooled response rate (RR0.95, P = 0.28).

Figure 5. Forest plot showing the meta-analysis of pyridoxine 400 mg versus 200 mg in the incidence of grade 2 or worse Hand-foot syndrome.

This forest plot is created by the software of RevMan 5.1.0. The diamond indicates the response rate (RR0.55, P = 0.02).