Wolf, S.L., Qin, R., Menon, S.P., Rowland, K.M., Jr, Thomas, S., Delaune, R., . . . Loprinzi, C.L. (2010). Placebo-controlled trial to determine the effectiveness of a urea/lactic acid-based topical keratolytic agent for prevention of capecitabine-induced hand-foot syndrome: North Central Cancer Treatment Group Study N05C5. Journal of Clinical Oncology, 28, 5182–5187.

To determine the effectiveness of a urea/lactic acid–based topical keratolytic agent (ULABTKA) for the prevention of capecitabine-induced hand-foot syndrome (HFS).

Eligible patients received their first dose of capecitabine at 2,000 or 2,500 mg/m² per day for 14 days, every 21 days. Patients then were randomized to the ULABTKA arm or placebo cream. Creams were applied to the hands and feet BID for 21 days over four consecutive cycles. Patients kept a daily diary. Toxicity data were collected at baseline and the end of each 21 day cycle. The primary end point was incidence of moderate or severe HFS in the first cycle, based on patient report. Secondary end points included the incidence of moderate or severe HFS by physician grading, times to grade, and physician determination.

• The study reported on a sample of 127 patients. Of 137 total patients enrolled, only 67 on study drug and 60 on placebo reported characteristics and outcomes.
• Twenty patients were aged younger than 50 years, 36 were aged from 50 to 60 years, and 71 were aged older than 60 years.
• The sample was 84% female, 16% male, and 96% Caucasian.
• Sixty-five percent of the sample had breast cancer, 23% had lung cancer, and 11% had colon cancer.
• All patients were to receive their first cycle of capecitabine; 85% were on metastatic treatment and 14% were on adjuvant treatment.

• Multi-site
• Outpatient
• North Central Cancer Treatment Group (NCCTG)

Patients were undergoing the active treatment phase of care.

This was a randomized, double-blind, phase 3 clinical trial.

• All patients were provided information regarding initial signs and symptoms of HFS.
• Patients completed a self-reported HFS diary daily.
• Physicians determined HFS grades for symptoms with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, at baseline and the end of each 21-day cycle.
• Patients completed a symptom experience diary at baseline and each week.
• Patients were queried about the occurrence of rash and diarrhea at each visit.

• No significant differences were observed in toxicities between the two groups across all visits.
• With regard to primary end point, the difference between the two study arms was not statistically significant. In fact, the incidence of moderate-to-severe HFS was higher in the treatment arm.

The use of urea/lactic acid for the prevention of HFS in patients receiving capecitabine therapy cannot be supported on the basis of this trial.

The primary end point only concerned the first 21-day cycle, rather than looking over the planned four cycles. This raises the question over whether more power could have existed to detect smaller differences. More patients received the lower dose of capecitabine.

Nurses should educate patients to limit or not use urea/lactic acid cream if starting on capecitabine.