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Overview of prophylactic management of multikinase inhibitor-induced adverse skin reactions

Healthcare providers are pivotal in preparing patients and managing their expectations prior to initiation of multikinase inhibitor treatment. The currently available evidence and recommendations for prophylactic skin treatment during multikinase inhibitor treatment are based on the following principles: 1) educating of patients with regards to prevention and management, 2) avoiding exposure to irritant agents, 3) diminishing stress over the skin, and 4) favouring the normal homeostasis and self-repairing of the skin. In this regard, general recommendations that should be given to patients are listed below:

  • Measures to prevent hand-foot skin reaction
    • A full body skin examination with a focus on hyperkeratotic areas on palms and soles1
    • Pedicure to remove any pre-existing hyperkeratotic areas or calluses that may predispose to hand-foot skin reaction1 prior to treatment initiation
    • Avoid friction, pressure and irritation to hands and feet
    • Nicely fitting shoes (no sandals, slippers, high heels or shoes that are too tight) and cotton socks
    • Wear gloves for washing, cleaning, working
    • Don’t wash hands too often, avoid hot water and use gentle cleansing oil
    • Use hand- or foot cream
    • Cushioning of frictional or high pressures zones of the skin that are prone to calluses2
    • Use of moisturising and keratolytic urea creams to control existing hand-foot skin reaction3
  • Measures for skin hydration and protection1
    • Patients should be advised to:
      • Reduce exposure of the skin to hot water, use lukewarm water instead
      • Reduce the frequency and duration of bathing or showering
      • Apply moisturiser twice a day and also directly after bathing/showering
      • Use bath/shower oil or mild moisturising soaps
      • Avoid extreme temperatures
  • Sun protection1, 4,5
    • Patients must be given adequate practical advice on appropriate sun-protective measures including:
      • Sunscreens with a sun-protection factor of at least 30 with good UVA protection should be recommended from March to September, in Europe (SPF 50 is recommended by some clinicians/certain countries)
      • Patients should also be advised to reapply sunscreen every two to three hours in case of outdoor activities
      • Protective clothing and hats should be worn when outside
  • Prophylactic antibiotics are used for papulopustular acneiform eruption1
    • Minocycline 100 mg daily
    • Doxycycline 100 mg daily
  • Nail care5, 6 
    • Patients should be advised to avoid
      • Trauma to the nail folds such as
        • Nail biting
        • Pushing back the nail cuticle
        • Tearing of skin around the nail
        • Cutting nails too short
        • Wearing shoes that are too tight
        • Household or manual work without wearing gloves
  • Secondary skin lesions4, 5
    • Sun protection (see above)
    • Baseline examination for preexisting hyperkeratosis, especially in patients with history of excessive sun exposure
    • Monitor patients every month for evidence of secondary skin lesions or keratoacanthoma lesions
  • Oral care7, 8
    • Patients should be assessed and educated on good oral hygiene methods
    • Advise to avoid hard, hot, sharp or spicy food
    • Assess the oral cavity regularly and advise to inform caregiver at first signs and symptoms of oral complications
    • Patients should use saline-based mouthwashes; acid- or alcohol-based mouthwashes should be avoided. To date, there is no evidence to support the use of one type of mouthwash over another.8 Rinsing the mouth to remove bacteria is key to good oral care 


  1. Lacouture ME, et al. The Oncologist. 2008;13:1001-1011.
  2. Wood LS, et al. Commun Oncol. 2010;7:23–29.
  3. McGuire DB, et al. Support Care Cancer. 2013;21:3165-3177.
  4. Sinha R, et al. British Journal of Dermatology. 2012;167:987–994.
  5. Brose MS, et al. Cancer Treat Rev. 2018;66:64-73.
  6. Robert C, et al. Lancet Oncol. 2005;6:491-500.
  7. Boers-Doets C, et al. Future Oncol. 2013;9:1883–1892.
  8. Boers-Doets C, et al. The Oncologist. 2012;17:135–144.

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