Yoshimoto, N., Yamashita, T., Fujita, T., Hayashi, H., Tsunoda, N., Kimura, M., . . . Iwata, H. (2010). Impact of prophylactic pyridoxine on occurrence of hand-foot syndrome in patients receiving capecitabine for advanced or metastatic breast cancer. Breast Cancer, 17, 298–302.

To assess the impact of prophylactic pyridoxine on hand-foot syndrome (HFS). The impact of urea ointment on HFS also was assessed.

Patients who were prescribed capecitabine at two hospitals between November 1, 2006, and October 30, 2007, received prophylactic pyridoxine 60 mg per day. The results were compared to those of a control group that did not receive prophylactic pyridoxine when the patients were prescribed capecitabine. Information on the prescription of urea ointment was available for the research group; 18 were prescribed urea ointment before HFS occurred.

• The study reported on a sample of 38 patients in the research group and 40 patients in the control group.
• Mean patient age was 55 years (range 31–88) for both groups.
• All patients in the research group were women. Gender in the control group is unknown.
• All patients had a cancer diagnosis.
• In the research group, capecitabine was given either as monotherapy or in combination with cyclophosphamide. This was the same in the control group, except some patients also received epirubicin.

• Multi-site
• Outpatient
   

Patients were undergoing the active treatment phase of care.

This was a retrospective study on patients treated with capecitabine with or without prophylactic pyridoxine.

• HFS was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
• Standard response criteria
• Time to HFS was estimated using the Kaplan-Meier method and compared with the same historical data using the log-rank test.

• Twenty of the 38 patients receiving prophylactic pyridoxine (53%) developed HFS, compared with 83% of the 40 historical control patients who received no pyridoxine. 
• Pyridoxine did not appear to reduce the severity of HFS, but a nonsignificant trend toward delayed onset of HFS existed among patients receiving pyridoxine prophylaxis versus those without.
• A nonsignificant trend toward less-severe HFS also existed among patients who were prescribed urea ointment. 

Study findings did not support the effectiveness of pyridoxine in preventing HFS. Application of urea ointment may reduce the likelihood of developing HFS and prevent exacerbation to more severe HFS.  

•  The sample size was small (fewer than 100).
• The research group was all women. The authors proposed this may have affected the results, as women generally tend to care more about the condition of their skin on their hands and feet than men.
• The study had a retrospective design.
• Different chemotherapies were used in the study and control groups.
• Very limited sample demographic information was provided to determine key group differences that may have affected outcomes.
   

Because the data regarding prophylactic use of pyridoxine from this study contrasted with prospective data from a randomized phase 3 trial in patients with gastrointestinal disease, strongly recommending this approach is difficult. Evidence in this study is weak, and numerous limitations exist.