Mar 02, 2015
By Shira Klapper, Senior Writer/Editor
As part of a randomized, controlled study out of China, patients with hepatocellular carcinoma (HCC) used a urea-based cream at the start of treatment with sorafenib. The goal of the study? To assess whether prophylactically using the cream affected the onset and severity of hand-foot skin reaction (HFSR), a dermatologic serious adverse side effect that frequently affects patients who take sorafenib, a multikinase inhibitor that is the standard therapy for HCC worldwide. This is the first study to look at the effects of taking the cream preventatively, at the onset of treatment, before any symptoms appear.
The study, published in the Journal of Clinical Oncology (JCO), found that over a 14-week period, incidence of HFSR—of any grade—was lower among patients who started using the urea-based cream at the start of treatment, compared to patients who received best supportive care alone. The Incidence of HFSR that was specifically grade 2 or higher was also lower among the prophylactic group. Patients who used the cream also experienced a significantly longer time to the onset of symptoms of HFSR and reported a higher quality of life, according to a questionnaire answered by patients. The study “Randomized Controlled Trial of the Prophylactic Effect of Urea-Based Cream on Sorafenib-Associated Hand-Foot Skin Reactions in Patients with Advanced Hepatocellular Carcinoma,” was published online, ahead of print, February 9, 2015.
Urea cream is widely used to treat HFSR, whose symptoms can include numbness, tingling, and painful swelling and blistering that affects patients’ hands and feet and may affect their ability to carry out activities of daily living.
Shedding light on the motivation behind the study, coauthor Sheng-Long Ye, MD, PhD, explained how the symptoms of HFSR can impact patients’ lives on many levels. “Though HFSR is not life-threatening, the dermatologic symptoms have an impact on quality of life in terms of physical, psychological, and social well-being”.
In addition, the symptoms of HFSR can often disrupt the cancer treatment—and therefore, prognosis. “Often, the symptoms reach a point where we have to reduce the dose for sorafenib,” said Dr. Ye. “The thought behind this study was that perhaps by administering the urea-based cream at the start of treatment, we could decrease the side effects and improve patients’ lives.”
Two patient groups: urea-based cream or care as usual
The study randomly assigned patients to two groups: 439 patients in the treatment group began using the 10% urea-based cream plus best supportive care three times a day starting on day one of sorafenib treatment. The 432 patients in the control group used best supportive care alone starting on day one of treatment; patients in the control group were allowed to start using the urea-based cream once symptoms began to appear. Patients’ symptoms were assessed every two weeks and at 14 weeks after the start of treatment.
In addition to physical symptoms, patients’ quality of life was measured through a self-assessment questionnaire that included 48 items. The questionnaire assessed the condition of feet, hands, and fingers and other parts of the body and the impact of these symptoms on the patients’ ability to sleep and perform daily activities and on their social life and mood.
Findings: Urea-based cream decreases symptoms
Fifty six percent of patients in the urea-based cream group experienced any grade of HFSR, compared to 73.6% in the group that received best supportive care alone. When it came to HFSR of grade 2 or higher, the incidence was 20.7% among the treatment group, compared to 29.2% among the control group. The treatment group also fared significantly better when it came to the time to first occurrence—symptoms appeared in the treatment group at 84 days after the first day of treatment, compared to 34 days among the control group. In addition, the questionnaires indicated that at weeks six and eight, HFSR symptoms had less impact on the daily activities of patients who used the urea-based cream since the start of treatment. There were no differences in the frequency of dose reductions between the two groups.
Sheng-Long Ye, MD, PhD, is a Professor of Medicine and Oncology, former Vice Chairman of the Liver Cancer Institute, and Chief of the Department of Hepatic Oncology at the Zhong Shan Hospital at Fudan University, in Shanghai.
Click here to read the abstract.
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ZhenGang R, Zhu K, Kang H, et al. Randomized controlled trial of the prophylactic effect of urea-based cream on sorafenib-associated hand-foot skin reactions in patients with advanced hepatocellular carcinoma. J Clin Oncol. Epub 2015 Feb 9.
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@ 2014 American Society of Clinical Oncology