Braik, T., Yim, B., Evans, A.T., Kassem, M., Mullane, M., Lad, T., . . . McDunn, S. (2014). Randomized trial of vitamin B6 for preventing hand-foot syndrome from capecitabine chemotherapy. The Journal of Community and Supportive Oncology, 12, 65–70.

To determine whether pyridoxine can prevent hand-foot syndrome (HFS) in patients with cancer being treated with capecitabine

Eligible patients were randomized to receive either pyridoxine at a dose of 100 mg per day plus capecitabine-containing chemotherapy or a placebo plus capecitabine-containing chemotherapy. The placebo pills did not visually match the pyridoxine pills although they were similar. The primary investigator and the treating oncologist were blinded to treatment groups. The potency of the pyridoxine was not tested, but the drug came from multiple lots over the course of the study. Pyridoxine or placebo treatment was initiated on the first day of capecitabine treatment. Adherence was assessed by a phone call to patients during the third week of each treatment cycle as well as by pill counting. Data were collected by the treating oncologist after each cycle of chemotherapy for up to four cycles. Three topical agents that contained urea or lactic acid were not permitted to be used during the study, Aqua Care^® medicated calamine lotion (.3%), Dr. Scholl’s^® Smooth Touch deep moisturizing cream, and Dove^® moisturizing cream wash.

• N = 77  
• MEAN AGE = 54.1 years
• MALES: 38%, FEMALES: 62%
• KEY DISEASE CHARACTERISTICS: All patients were diagnosed with a cancer requiring capecitabine therapy and had never received capecitabine before.  
• OTHER KEY SAMPLE CHARACTERISTICS: Ethnicities included African American (53%), white (21%), Hispanic (18%), and Asian (7%). Inclusion criteria included age reater than 18 years old, an Eastern Cooperative Oncology Group score of 0–2, a life expectancy > 6 months, not taking vitamin B supplements, no prior HFS, no contraindication to chemotherapy, and adequate renal and liver function. Exclusion criteria included previous treatment for HFS, hypersensitivity to pyridoxine, immunosuppression or positive human immunodeficiency virusserology, and pregnancy or lactation.

• SITE: Single-site    
• SETTING TYPE: Not specified    
• LOCATION: John H. Stroger Jr. Hospital of Cook County, Chicago, IL (Hematology and Oncology Division)

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Adults  

Randomized, double-blinded, placebo-controlled trial

• The National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3 toxicity grading criteria was used to grade HFS.

HFS developed in 26% of patients in the pyridoxine group (n = 38) and 21% patients in the placebo group (n = 39). In both groups, 16% developed grade 2 or 3 HFS. No significant differences in HFS grades were observed in the two arms of the study.

Based on a review of the study’s primary endpoints (e.g., HFS incidence, grade), there is no true benefit from using prophylactic vitamin B6 in patients with cancer receiving capecitabine-containing chemotherapy.

• Small sample (< 100)
• Risk of bias (sample characteristics)
• Key sample group differences that could influence results
• Other limitations/explanation: Low percentage of patients of Asian ethnicities; included patients who received doses of capecitabine that were lower than the standard dose, which might explain the lower incidence of HFS in the studied population

The results of this study demonstrated that administering pyridoxine (vitamin B6) to patients receiving capecitabine-containing chemotherapy did not lower the incidence or grade of HFS. Other strategies should be implemented to prevent capecitabine-induced HFS.