title: Randomized controlled trial of the prophylactic effect of urea-based cream on sorafenib-associated hand-foot skin reactions in patients with advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  In this randomized, open-label trial, 871 patients with advanced HCC throughout China were treated with 10% UBC three times per day plus best supportive care (BSC; n = 439) or BSC alone excluding all creams (n = 432), starting on day 1 of sorafenib treatment, for up to 12 weeks. HFSR was assessed every 2 weeks and at 14 weeks for patients completing the study. Once HFSR occurred, patients were allowed any cream, including a UBC.
  
  
  RESULTS
  The 12-week incidence of any grade HFSR was significantly lower in the UBC group versus the BSC-alone group (56.0% v 73.6%, respectively; odds ratio [OR], 0.457; 95% CI, 0.344 to 0.608; P < .001), as was the incidence of grade ≥ 2 HFSR (20.7% v 29.2%, respectively; OR, 0.635; 95% CI, 0.466 to 0.866; P = .004). Median time to first occurrence of HFSR was significantly longer in the UBC group than the BSC-alone group (84 v 34 days, respectively; hazard ratio, 0.658; 95% CI, 0.541 to 0.799; P < .001). Elevated AST was associated with increased risk of HFSR but did not alter the treatment effect of UBC. UBC plus BSC, compared with BSC alone, did not affect the sorafenib dose reduction or interruption rate (9.1% v 11.8%, respectively; P = .1937), response rate (11.1% v 10.1%, respectively; P = .6674), or disease control rate (98.8% v 98.2%, respectively; P = .5350) at week 12.
  
  
  CONCLUSIONS
  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 with BSC. Blinded, randomized, placebo-controlled trials to determine the role of UBC on the incidence and severity of HFSR are warranted.
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: ZhengGang
authors: Z
authors: Ren
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: KangShun
authors: K
authors: Zhu
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: HaiYan
authors: H
authors: Kang
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: MinQiang
authors: M
authors: Lu
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: ZengQiang
authors: Z
authors: Qu
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: LiGong
authors: L
authors: Lu
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: TianQiang
authors: T
authors: Song
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: WeiPing
authors: W
authors: Zhou
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: Hui
authors: H
authors: Wang
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: WeiZhu
authors: W
authors: Yang
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: Xuan
authors: X
authors: Wang
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: YongPing
authors: Y
authors: Yang
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: LeHua
authors: L
authors: Shi
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: YuXian
authors: Y
authors: Bai
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China.
authors: XiaoFeng
authors: X
authors: Guo
authors: ZhengGang Ren and Sheng-Long Ye, Liver Cancer Institute, Zhongshan Hospital, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education; ZengQiang Qu, WeiPing Zhou, and LeHua Shi, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai; KangShun Zhu and MinQiang Lu, The Third Affiliated Hospital of Sun Yat-sen University; LiGong Lu, Guangdong Provincial People's Hospital, Guangdong; HaiYan Kang, 301 Military Hospital; YongPing Yang, 302 Military Hospital; XiaoFeng Guo, Chinese Anti-Cancer Association, Beijing; TianQiang Song, Tianjin Cancer Hospital, Tianjin; Hui Wang, Jilin Provincial Tumor Hospital, Jilin; WeiZhu Yang, Union Hospital of Fujian Medical University, Fujian; Xuan Wang, The 81 Hospital of the Chinese People's Liberation Army, Nanjing; and YuXian Bai, Heilongjiang Provincial Cancer Hospital, Heilongjiang, People's Republic of China. slye@shmu.edu.cn.
authors: Sheng-Long
authors: SL
authors: Ye
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy*; D002681:China; D004655:Emulsions / Q000008:administration & dosage*; D005260:Female; D060831:Hand-Foot Syndrome / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives*; D016017:Odds Ratio; D010671:Phenylurea Compounds / Q000009:adverse effects*; D011788:Quality of Life; D012867:Skin / Q000187:drug effects; D000077157:Sorafenib; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014508:Urea / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D010671:Phenylurea Compounds; D009536:Niacinamide; D014508:Urea; D000077157:Sorafenib