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Reactive management of hand-foot skin reaction induced by multikinase treatment

General recommendation: Severe HFSR can be painful and interfere with normal daily activities. It is essential to educate patients before treatment, to prioritise prevention, and to ensure early detection and prompt treatment of symptoms if these occur.1

Treatment overview

Treatment for HFSR in patients receiving multikinase inhibitors is based largely on anecdotal evidence and expert opinion.2

Supportive measures should be initiated promptly when symptoms are noted. This may include application of cold packs, wearing thick cotton gloves and/or socks at night, use of moisturising creams for relief and application of a keratolytic cream to aid exfoliation.3, 4 In severe cases, temporary relief from the itching, burning, pain and swelling of HFSR may be obtained using topical preparations containing one or more of a vasoconstrictor (e.g. phenylephrine), astringent (e.g. witch hazel), anaesthetic (e.g. pramoxine) and protective agents.5 Keratolytic options include a 20%–40% urea-based cream or salicylic acid 6%;1,4 these should only be applied to hyperkeratosis-affected areas as they may cause ulcers on unaffected skin.5 Alpha hydroxyl acids (5%–8%) may be applied liberally twice a day.1 Hydrocolloid or alginate dressings can be used to protect pressure points and may aid healing.5

A potent topical corticosteroid such as clobetasol propionate 0.05% may be initiated at the onset of grade 1 or grade 2 symptoms.1, 6-9 A combination preparation with clobetasol propionate 0.05% and salicylic acid 3.5% may be considered.5 Pain management is required for grade 2 or higher symptoms; lidocaine gel 4% may be tried.5, 6 These measures should be continued for grade 3 symptoms, but treatment should be withheld for at least 7 days or until HFSR improves.1, 4 Topical antibiotics may be needed to treat blisters and erosions.8 Wet lesions should be swabbed and oral antibiotics initiated as appropriate.5

For mild to moderate pain, apply topical anesthetics: use for instance lidocaine HCl gel 4%. For more severe pain, patients should be switched to oral analgesics if needed. 5,6 

Following improvement of an acute episode of HFSR, tender hyperkeratotic lesions may develop.1 Topical corticosteroids (e.g. fluocinonide 0.05%, clobetasol 0.05%) may be used to treat severe inflammation and painful erythematous areas.10 Immersion of hands and feet in cold water may relieve pain.10 Other options for treating these lesions include urea 40% cream, tazarotene 0.1% cream or fluorouracil 5% cream.1

After treatment of a callus, an emollient cream should be applied to prevent the rapid recurrence of hyperkeratotic lesions.1 Non-urea-based creams should also be liberally applied to unaffected areas of the hands and feet.1

Patients should be evaluated weekly. With the second or third occurrence of hand-foot skin reaction intensifying supportive measures is advised. If symptoms worsen despite the intensified measures, drug interruption or discontinuation should be considered.

Table 30: Management of hand-foot skin reaction associated with multikinase by CTCAE grade4, 6-9




  • Avoid hot water and alcohol-containing hand products
  • Wear thick cotton gloves and/or socks at night
  • Moisturising creams
  • Urea 20% cream twice daily on the calluses and hyperkeratosic areas
  • Clobetasol 0.05% cream once daily


  • Continue treatment as for grade 1
  • Pain management with lidocaine 4% gel or oral analgesics as needed (NSAIDs, COX-2 inhibitors, or paracetamol)
  • Topical antibiotics to treat blisters and erosions


  • Continue supportive treatment as for grades 1 and 2
  • If pain is not controlled with classical analgesics, GABA agonists or narcotics may be considered


  • Not applicable

NSAIDs: nonsteroidal anti-inflammatory drugs; GABA: gamma-aminobutyric acid


  • Emollient cream
  • Alpha hydroxyl acids 5%–8% (e.g. glycolic acid)
  • Salicylic acid 6%
  • Urea 20-40% cream
  • Lidocaine 4% gel
  • Oral analgesia (e.g. codeine, pregabalin)
  • Clobetasol 0.05% ointment
  • Fluocinonide 0.05% cream
  • Tazarotene 0.1% cream
  • Fluorouracil 5% cream

Multikinase inhibitor treatment

Continue with/withhold the selected multikinase inhibitor treatment regimen, as recommended in the current and relevant SPC and according to the patient’s condition.


  1. Wood LS et al. Commun Oncol. 2010; 7: 23-29.
  2. Anderson R et al. Oncologist. 2009; 14(3): 291-302.
  3. De Wit M et al. Support Care Cancer. 2014; 22 : 837-46.
  4. Lacouture ME et al. Oncologist. 2008; 13: 1001-1011.
  5. Boers-Doets CB. The TARGET SYSTEM. Approach to assessment, grading, and management of dermatological & mucosal side effects of targeted anticancer therapies. ISBN 978-94-92070-00-5. 2014.
  6. Balagula Y et al. J Support Oncol. 2010; 8(4): 149-161.
  7. Grothey A et al. Oncologist. 2014;19:669-80.
  8. Krishnamoorthy SK et al. Therap Adv Gastroenterol. 2015;8:285-97.
  9. McLellan B et al. Ann Oncol. 2015;26:2017-26.
  10. Gomez P & Lacouture ME. Oncologist. 2011; 16: 1508-1519.

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