Prevention of Hand-foot Skin Reaction
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Study type: Interventional

Summary: 
      Sorafenib-induced hand-foot skin reaction (HFSR) is a dose-dependent side effect in patients
      with advance hepatocellular carcinoma (HCC). The appropriate prophylactic dose of urea-based
      cream and comparison of its effectiveness with other creams remain unclear. The aim of this
      study was re-validating the prophylactic HFSR incidence density and cutaneous wetness of 10%
      urea-based cream on sorafenib-induced HFSR in patients with advanced HCC.
    

Detailed description: 
      Methods

      Patients

      This study population consisted of patients with (1) HCC by proof of pathology, (2) presence
      of tumor thrombus in the main trunk of the portal vein or the first-order branches of the
      portal vein with minimal ascetics or with no ascetics by abdominal CT scan, (3) Child-Pugh
      liver function class A, (4) planning to receive oral sorafenib 400 mg twice per day, (5) age
      of 20 or more years old, and (6) able to communication in Chinese, Taiwanese or Hakka.
      Patients with (1) encephalopathy, psychosis, cognition impairment, blindness or hearing
      impairment, (2) allergic history to urea, (3) present ulceration, blisters, infective
      problems on the palms or soles, or (4) previous surgery, systematic chemotherapy or frequent
      radial ablation were excluded.

      Research procedure

      This is a randomized double-blind experiment study. Sample size was estimated by the G. power
      software version 3.1, which was set with logistic regression, odds ratio: 3.8, and power:
      0.80. The estimated sample size should be 125 at least. This study, there was recruited 129
      patients (43 patients in each groups). All eligible patients were recruited from Taipei
      Veterans General Hospital between January 1st and December 31th, 2014. They were randomly
      assigned in a ratio of 1:1:1 to treat with best supportive care plus moisturizing cream (A
      group), BSC plus 10% urea-based cream (B group) and BSC alone (group C which is comparison
      group),by method of EXCEL random sampling. A case manager recruited the eligible patients who
      also conducted informed consent and patient education. A research employee had
      responsibilities to record patients' demographic data, provide non-label cream and check
      previous container of the cream that should be exhausted. A medical oncologist or a nurse had
      responsibilities to assess patients' severity of HFSR and cutaneous wetness. The assessment
      was done on 3 days before starting sorafenib treatment and each 7 days after the starting,
      total 9 times. Creams were provided after the assessment. When patients developed HFSR, they
      will be referred to receive the most appropriate management.

      Interventions

      Interventions for group C (comparison group) who received BSC alone were (1) informed of
      potential presentations of HFSR, (2) asked for wearing waterproof gloves before execute
      household or work with water, (3) provided the method of contacting with healthcare
      specialists for confirming early diagnosis of HFSR, and (4) asked for self-report when they
      occurred symptoms of HFSR. The A group with BCS plus moisturizing cream received the
      interventions as the comparison group, was given the moisturizing cream (dimethicone,
      fragrance free, Aveeno, United States) for 9 times and was instructed how to use the cream.
      The education of usage included (1) using the cream twice a day from 3 days before starting
      sorafenib and each week post starting sorafenib, (2) scooping out nut-sized cream with a
      unique spoon each time, (3) gently applied the cream evenly on symmetrical palms below wrists
      and symmetrical soles below ankles each time, (4) wore unique cotton gloves immediately after
      the appalment of cream for 30 minutes each time. A B group with BCS plus 10% urea-based cream
      had the similar interventions as the A group with BCS plus moisturizing cream except being
      given the cream container with different component (10% urea; Sipharr, Taiwan). The outlook
      of the containers with the two kinds of cream was the same. All the cream looks white and
      grey.

      Outcomes and assessment

      Data of con founders and two end-points, incidence density of HFSR and cutaneous wetness,
      were collected. The con-founders included gender, age, numbers of chronic illnesses, numbers
      of metastatic regions as well as levels of white count, hemoglobin, bleeding time, liver
      enzymes, albumin and electrolyte.

      The grades of HFSR were assessed by NCI-CTCAE version 4, which was developed by Dueck et al.
      This is an available psychometric patient-reported instrument. Body water with 33% or less
      meant dry skin, 34% to 37% meant mild dry skin, 38% to 42% meant general status, 43% to 46/%
      was mild moisty skin and 47% or more presented moisty skin. When using the scanner, examiners
      had to confirm whether it tied to fix on the skin.

      Ethical considerations

      This study was approved by the Institution Review Board of the Taipei Veterans General
      Hospital (2013-13-009B). Informed consent was obtained from all patients by a case manager on
      3 days before starting sorafenib. Patients were explained the study protocol and were
      educated self-care skills by the case manager. All of them were well aware that their rights
      will be protected, the risk of participation will be limited to the lowest and most suitable
      management will be arranged when they developed sorafenib-induced HFSR.
    

Intervention name(s): best support care; moisture cream; 10% urea-based cream
Intervention type(s): Other; Other; Other
Intervention description(s): Best support care; BSC plus moisture cream; BSC plus 10% urea-based cream.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Prevention
Keywords: hand-foot skin reaction; side effect of sorafenib; symptom related to target therapy; efficacy of urea-based cream; symptom management