von Gruenigen, V., Frasure, H., Fusco, N., DeBernardo, R., Eldermire, E., Eaton, S., & Waggoner, S. (2010). A double-blind, randomized trial of pyridoxine versus placebo for the prevention of pegylated liposomal doxorubicin-related hand-foot syndrome in gynecologic oncology patients. Cancer, 116, 4735–4743.

To compare the efficacy of pyridoxine versus placebo for the prevention of hand-foot syndrome (HFS) in patients with recurrent ovarian, metastatic breast, or endometrial cancer who received pegylated liposomal doxorubicin (PLD) chemotherapy. A secondary objective was to compare quality of life (QOL) between patients who experienced HFS during chemotherapy and those who did not.  

Patients were randomly assigned to receive pyridoxine 100 mg BID (group A) or placebo (group B). Patients also received standard HFS education and completed a QOL questionnaire. Incidence of HFS was compared between groups.

• The study reported on a sample of 34 women (18 in group A and 16 in group B).
• Mean patient age was 64 years (range 45–81).
• All patients had recurrent ovarian, breast, or endometrial cancer and were receiving PLD.
• Five patients (3 in group A and 2 in group B) were not evaluable for HFS assessment.
• The sample was 85% Caucasian.
• Five patients receiving pyridoxine and five patients receiving placebo had disease progression and died during PLD therapy.

• Single site
• Outpatient

Patients were undergoing the active treatment phase of care.

This was a randomized, double-blind, placebo-controlled trial.

• Functional Assessment of Cancer Therapy (FACT) QOL analyses    
• Chi-square or Fisher exact tests
• National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0
   

• Overall, 52% of patients developed HFS (all grades), and 35% developed grade 2 or 3 events. No grade 4 events were observed.
• Fifty-three percent of patients in group A developed HFS compared to 50% of patients in group B.
• No difference existed between groups for grade 2 or 3 events. In addition, no differences existed between groups in global or domain QOL scores after cycle 3 of PLD.
• The physical domain declined for patients with grade 2 or 3 HFS; however, the decline was not statistically significant.

Pyridoxine as administered in the current study did not prevent HFS in patients who received PLD. No difference existed in the incidence of HFS between patients who received prophylactic pyridoxine and those who received placebo. In addition, the HFS rash appeared to be tolerable in most patients because it did not disrupt patient-rated QOL in this study.

• The sample size was small (fewer than 100 patients).
• The population was all women, and most were Caucasian.
• The total sample size was reduced to 24 patients because of reactions during chemotherapy and death during PLD therapy. 
• QOL results are questionable because the line item in the tool used in the physical well-being domain relates to overall side effects of treatment and does not specifically address HFS.

Findings do not support the effectiveness of pyridoxine in the prevention of HFS. The study was likely underpowered. Additional research is needed on strategies to prevent and manage HFS.