What Healthcare Professionals Should Know

Recommendations for the prevention of cutaneous toxicities with multikinase inhibitor therapies are based on practices utilised in clinical studies, post-marketing experience and reports and empirical results based on clinical experience, including those of the authors. In all instances, patient education is an important component of management.


Frequent monitoring for rash, particularly at the beginning of therapy, may be useful. Preventive measures, such as regular use of alcohol-free emollients from the start of treatment, use of mild soaps, and avoiding extreme temperatures and direct sun exposure, may help prevent or reduce the severity of rash.1,2

Hand-Foot Skin Reaction

 A complete examination of hands and feet prior to starting treatment may ensure that any changes associated with HFSR are better identified.1 Patients with hyperkeratotic areas at baseline may be given a pedicure using sterile instruments prior to the start of the therapy.2–5 Prevention should include cushioning callused areas and the application of moisturising and keratolytic creams to control any existing palmar and plantar hyperkeratosis. During the first 2 to 4 weeks of treatment, it is vital to minimise the development of blisters by avoiding vigorous exercise and other activities that place stress mainly through friction on the hands and feet, including avoiding tight-fitting footwear.6,7 Orthotic devices to normalise weight-bearing and prevent friction may also be considered.3,8

Dry Skin and Pruritus

Possible triggers of pruritus should be investigated by considering the patient’s medical history together with a thorough clinical assessment.5 Based on the expert’s experience, moisturising is an essential component of preventing xerosis and pruritus, and use of moisturisers that are free of possible irritants is prudent.

Nail Changes

Preventive strategies include wearing comfortable shoes, putting on gloves while cleaning,3 keeping the hands dry as much as possible, minimising friction or pressure on the nail fold, avoiding picking or manipulating of the nail, and applying petrolatum around the nails to retain moisture.9 Patient education regarding appropriate clipping of the nail plates appears to be also beneficial, including avoidance of cutting the lateral margins of the nail plate shorter than the digit tip.


An oral care plan should be developed before treatment and evaluated periodically,3 taking into account such factors as use of a soft toothbrush or swab; regular rinsing with an alcohol-free mouthwash, saline solution or bicarbonate; eating soft, room-temperature foods and avoiding hot, spicy or acidic food and drinks; and keeping a good oral hygiene.1,10


For multikinase inhibitors associated with photosensitivity, regular application of sunscreen with a sun protection factor (SPF) of at least 30 is required.2 Protective clothing and hats should be worn when outside.

Keratoacanthomas and Squamous Cell Carcinomas

Patients should be exhaustively explored at baseline and regularly monitored for the development of lesions as the treatment with the drug advances in order to ensure early and appropriate treatment.5,11 Inclusion of dermatologists as part of a multi-disciplinary team to help in early diagnosis is advised, especially in those patients that have presented a history of intense and frequent sun exposure.


1De Wit M, et al. Prevention and management of adverse events related to regorafenib. Support Care Cancer. 2014;22:837–846.
2Walko CM, Grande C. Management of common adverse events in patients treated with sorafenib: nurse and pharmacist perspective. Semin Oncol. 2014;41:S17–S28.
3Lacouture ME, et al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist. 2008;13:1001–1011.
4Anderson R, et al. Search for evidence-based approaches for the prevention and palliation of hand-foot skin reaction (HFSR) caused by the multikinase inhibitors (MKIs). Oncologist. 2009;14:291–302.
5Gutzmer R, et al. Cutaneous side effects of new antitumor drugs: clinical features and management. Dtsch Arztebl Int. 2012;109:133–140.
6Autier J, et al. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor. Arch Dermatol. 2008;144:886–892.
7Wood LS, et al. Practical considerations in the management of hand–foot skin reaction caused by multikinase inhibitors. Commun Oncol. 2010;7:23–29.
8McLellan B, Kerr H. Cutaneous toxicities of the multikinase inhibitors sorafenib and sunitinib. Dermatol Ther. 2011;24:396–400.
9Potthoff K, et al. Interdisciplinary management of EGFR-inhibitor-induced skin reactions: a German expert opinion. Ann Oncol. 2011;22:524–535.
10Kollmannsberger C, et al. Sunitinib in metastatic renal cell carcinoma: recommendations for management of noncardiovascular toxicities. Oncologist. 2011;16:543–553.
11Balagula Y, Lacouture ME, Cotliar JA. Dermatologic toxicities of targeted anticancer therapies. J Support Oncol. 2010;8:149–161.

Last update: 22 August 2014