Ren, Z., Zhu, K., Kang, H., Lu, M., Qu, Z., Lu, L., . . . Ye, S. L. (2015). Randomized controlled trial of the prophylactic effect of urea-based cream on sorafenib-associated hand-foot skin reactions in patients with advanced hepatocellular carcinoma. Journal of Clinical Oncology, 33, 894–900. 

To assess whether urea-based cream (UBC) has prophylactic benefits on sorafenib-induced hand-foot skin reaction (HFSR) in patients with advanced hepatocellular carcinoma (HCC)

Patients were randomized to the intervention or control group. Patients in the intervention group received 10% UBC three times a day plus best supportive care (BSC), and those in the control group received BSC alone starting on day 1 of sorafenib treatment for up to 12 weeks. Once HFS developed, patients were allowed to use any creams per the treating physician. HFSR was evaluated every two weeks for 12 weeks, and an additional follow-up assessment was conducted at 14 weeks.

• N = 699
• AGE = 20–86 years
• MALES: 86%, FEMALES: 14%
• KEY DISEASE CHARACTERISTICS: Advanced HCC
• OTHER KEY SAMPLE CHARACTERISTICS: Performance status, previous anticancer therapy, history of disease

• SITE: Multi-site    
• SETTING TYPE: Not specified  
• LOCATION: 64 centers throughout China

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care, palliative care 

• Investigator-initiated, randomized, open-label, phase-III, multicenter clinical trial

• Patient-reported questionnaire
• HFSR evaluated by physician at each visit with Common Terminology Criteria of Adverse Events (CTCAE), version 3, every two weeks for 12 weeks

During the 12-week study, the patients receiving prophylactic UBC plus BSC had a significantly lower incidence and severity of HFSR than those receiving only BSC at each study visit (p < 0.001) for the entire 12-week study period (p < 0.001). At each study visit, the incidence of any grade HFSR was lower in the study group (p < 0.001). The time to first occurrence was significantly longer in the UBC group (p < 0.001). The rates of grade II and grade III HFSR were lower in the experimental group compared to the controls (p = 0.004).

UBC prophylaxis in patients with advanced HCC starting sorafenib reduced HFSR rates, extended the time to first occurrence of HFSR, and improved patient quality of life compared to BSC.

• Risk of bias (no blinding)
• Unintended interventions or applicable interventions not described that would influence results
• Findings not generalizable
• “Blinded, randomized, placebo-controlled trials to determine the role of UBC on the incidence and severity of HSFR are warranted.”
• The UBC and BSC group had 85 nonevaluable patients resulting in 354 patients evaluable for time to first HFSR. The BSC group had 87 nonevaluable patients resulting in 345 patients evaluable for time to first HFSR.

UBC plus BSC appears to be of benefit in this particular population of patients receiving sorafenib for advanced HCC. Although this cannot be generalized to other populations, it is worth suggesting to patients as they begin this therapy. Understanding the limitations of this study allows nurses to educate patients appropriately and supports their decisions to add UBC to their care.