Many investigators have studied for prevention and care of Hand-Foot Skin Reaction(HFSR), and urea cream is typical representative. Recent study was performed prevention effect of urea cream for Hand-Foot Skin Reaction(HFSR) on 871 Chinese. But the study did not designed as placebo-control group and it had big defect in double-blinded. Therefore, it needs complementary study as double-blinded placebo-controlled trial and effect of urea cream on Korean patient group.
Sorafenib is multiple tyrosine kinase inhibitor. It blocks path that such as Raf-1, Vascular Endothelial Growth Factor Receptor (VEGFR), Platelet-Drived Growth Factor Receptor-β (PDGFR-β), c-Jit, Flt-3. Sorafenib was known to increase life rate about processed hepatocellular carcinoma. So it is advised as standard treatment for liver cancer patient who has processed Barcelona Clinic Liver Cancer (BCLC) disease period C. Sorafenib related side effect has reported such as fatigue, diarrhea, vomit, nausea, pruritus, depilation, Hand-Foot Skin Reaction(HFSR). Among the symptoms, Hand-Foot Skin Reaction(HFSR) is the most occurrence after using sorafenib and major reason of drug dose de-escalation, it function as decrease anti-cancer effect of sorafenib. It is known for the reason of Hand-Foot Skin Reaction(HFSR) occurrence is caused by tyrosine kinase inhibitive action, and its characteristic symptom is known as keratocyte necrosis, dermal edema, parakeratosis, hyperkeratosis. The level is categorized grade 1,2,3 according to the severity. The result of meta-analysis of 24 clinical trials that contained 6000 patients, Hand-Foot Skin Reaction(HFSR) occured 39% of sorafenib used patients and 9% of total patients had grade 3 Hand-Foot Skin Reaction(HFSR). But prevalence rate on hepatocellular carcinoma patients who used sorafenib is about 51% on Japanese, 45% on Asia-pacific patient (inclusive Korean) and 73.6% on Chinese. Prevalence rate of Hand-Foot Skin Reaction(HFSR) is different from result of each study, but about 50% of sorafenib used patients has had Hand-Foot Skin Reaction(HFSR) generally and Asian has more higher degree of prevalence rate. Therefore, prevent and care of Hand-Foot Skin Reaction(HFSR) on Korean hepatocellular carcinoma patients who used sorafenib is required. Urea cream is typical representative for prevention and care of Hand-Foot Skin Reaction(HFSR). As stability-guaranteed drug, it is relatively cheap, locally affect and has used for psoriasis treatment. Also it is known for curative effacement on Hand-Foot Skin Reaction(HFSR) after use tyrosine kinase inhibitor such as sorafenib, sunitinib. Therefore, it needs complementary study as double-blinded placebo-controlled trial and effect of urea cream on Korean patient group.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
288
Sorafenib 400mg (twice daily), Spread urea cream (urea 20%)
Sorafenib 400mg (twice daily), Spread placebo cream (urea 0%)
Korea University Guro Hospital
Seoul, South Korea
Cumulative incidence of Hand-Foot Skin Reaction(HFSR) on each group
Comparison of cumulative incidence of HFSR between placebo group and urea cream group
Time frame: 12 weeks treatment
Cumulative incidence of severe HFSR on each group
Comparison of cumulative incidence of severe HFSR (grade 2 or grade 3) between placebo group and urea cream group
Time frame: 12 weeks treatment
Incidence of dose reduction or discontinuation of sorafenib due to HFSR on each group
Comparison of incidence of dose reduction or discontinuation of sorafenib due to HFSR on each group
Time frame: 12 weeks treatment
Assessment of Quality Of Life (QOL)
Assessment of QOL related to HFSR using The Hand-Foot Skin Reaction and Quality of Life Questionnaire (HF-QoL) scoring system. HF-QOL instrument comprises a 20-item symptom scale and an 18-item daily activity scale. Each item was scored from 0 (not at all) to 4 (always or extremely). Therefore, the range of score for HF-QoL was from 0 to 152 points. (Ref. Anderson et al. The Oncoligist 2015;20:831-838)
Time frame: 12 weeks treatment
Overall survival
Overall survival of patients
Time frame: 12 weeks treatment
Tumor response
Tumor response using mRECIST criteria
Time frame: 12 weeks treatment
Other side effect
The occurrence rate of other side effect excluding HFSR
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Time frame: 12 weeks treatment
Incidence of HFSR on 2, 4, 8, and 12 weeks on each group
Comparison of incidence of HFSR on 2, 4, 8, and 12 weeks between placebo group and urea cream group
Time frame: 2, 4, 8, and 12 weeks