Prophylaxis and treatment

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What healthcare professionals should do to treat side effects of multikinase inhibitor treatment

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 founded on clinical experience, including those of the authors.  Effective management of these toxicities involves a multimodal strategy that includes patient education, prophylactic and supportive care, and dose modifications (flexible dosing ).1-4 

Persistent and visible skin symptoms often obstruct the daily activities of patients, work and social functions and the ensuing physical and psychological burden may even influence their compliance to treatment.2 Hence, patient education on the potential drug-related cutaneous side effects associated with multikinase inhibitors is key for successful management and prevention of these side effects. Cumulative experience arising from clinical trials and clinical practice with other targeted anti-cancer agents such as EGFR-inhibitors, has demonstrated that pre-emptive rather than reactive therapeutic strategies are more efficient in controlling the different side effects caused by these agents.4,5 

In the case of pre-emptive measures not being sufficient to avoid the appearance of adverse events, early initiation of appropriate effective therapeutic measures is crucial for adverse event management and to maintain multikinase inhibitor dose intensity. In this regard, active participation of the patient is recommended to encourage rapid establishment of contact with the patient’s healthcare provider upon the initial appearance of symptoms. Such a strategy will allow for appropriate treatment of the problem and will lead to a faster recovery from the side effect, and will also help avoid any dose interruptions.

Acneiform rash: Nowadays acneiform rash with MTK inhibitors is most often managed with a prophylactic treatment regimen consisting of oral tetracycline antibiotics, a topical emollient and sun protection measures. Frequent monitoring for rash, particularly at the beginning of therapy, may be useful.6-10

Patients should take extra care with their skincare and avoid any identified conditions or irritants that may worsen the rash, as well as notifying their healthcare team early upon symptom onset.

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.6 Patients with hyperkeratotic areas at baseline may be given a pedicure using sterile instruments prior to the start of the therapy.7, 11–13 Prevention should include cushioning callused areas or frictional or high pressure 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 as well as sandals, slippers or high heels.14-15 Orthotic devices to normalise weight-bearing and prevent friction may also be considered.11, 16 Wearing gloves is advised to do manual labour (e.g. wash the dishes, cleaning, gardening etc.).

Guidance on skin care and protection should be provided for prevention of HFSR.6, 12 Patients should be encouraged to maintain frequent communication with their healthcare team to ensure symptoms are detected and managed as soon as possible.5, 11 Patients should avoid pressure and friction on the skin, or traumatic activity, as well as consider wearing gloves or protective socks if a potentially traumatic activity is planned.

Dry skin and pruritus: Possible triggers of pruritus should be investigated by considering the patient’s medical history together with a thorough clinical assessment.13 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. For patients with pre-existing conditions such as eczema the usual skin care should be intensified and for those with active rosacea, eczema or acne, a dermatologist should be consulted.10 

Patients should be advised to use tepid water, minimise showering, avoid soaps, and use topical emollients (fragranced or unfragranced, whichever the patient feels comfortable with) that are not too greasy to avoid occlusion of the follicles.18 Based on the authors’ experience, use of moisturisers immediately after bathing may allow better hydration of the skin and vigorous drying of the skin should be avoided to minimise irritation.

Nail changes (paronychia): Preventive strategies include wearing comfortable shoes, putting on gloves while cleaning, keeping 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.8,15 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.

Stomatitis: An oral care plan should be developed before treatment and evaluated periodically,11 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.6, 18 Evaluating the use of dental appliances (e.g. dentures, braces etc.) and possibly an overall assessment by a dental professional may be necessary. Making patients aware to contact their HCP at the onset of any symptoms of mucositis is also needed.5

Photosensitivity: Patients should be alerted to the likelihood of photosensitivity and should employ effective photoprotection strategies. For multikinase inhibitors associated with photosensitivity, regular application of sunscreen with a sun protection factor (SPF) of at least 30 is required.7-8 In some countries, SPF 50 is recommended. Protective clothing and hats should be worn when outside.

Keratoacanthomas and squamous cell carcinomas: Patients should be exhaustively examined 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.13, 18-19 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 excessive sun exposure.

Patients should be alerted to this potential toxicity and should themselves be advised to monitor their skin to potentially allow earlier identification of such lesions. Avoiding sun exposure or using appropriate protective measures against this stress factor is paramount.19

The table below provides a summary of key points for HCP to know and patients to do, in order to prevent and manage common skin toxicities while under treatment with multikinase inhibitors.

Table 27: What the Healthcare Provider (HCP) should know and patients do

Skin toxicity What HCP should know What patients can do
Applicable to all skin related toxicities
  • Patient education about toxicity (causes and management)
  • Pre-emptive management, if possible
  • Provide guidance on skin care and protection
  • Consider options for flexible dosing
  • Adopt proactive attitude
  • Notify healthcare team as early as possible upon symptom onset
Rash
  • Prophylactic treatment regimens include oral tetracycline antibiotics, a topical emollient and sun protection measures
  • Frequent monitoring for rash, particularly at the beginning of therapy, should be undertaken
  • Take extra care with skincare
  • Avoid any identified conditions or irritants that may worsen the rash
Hand-foot skin reaction (HFSR)
  • A complete examination of hands and feet prior to starting treatment
  • Patients with hyperkeratotic areas at baseline may be given a pedicure prior to the start of the therapy
  • Prevention should include cushioning callused areas or frictional or high pressure areas and the application of moisturising and keratolytic creams to control any existing palmar and plantar hyperkeratosis
  • Consider providing orthotic devices to normalise weight-bearing and prevent friction may also be considered
  • During the first 2 to 4 weeks of treatment, advice should be provided with regards to minimising the development of blisters (i.e. by avoiding vigorous exercise and other activities that place stress mainly through friction on the hands and feet, including avoiding tight-fitting footwear as well as sandals or slippers), as well as wearing gloves to do manual labour (e.g. wash the dishes etc.)
  • Avoid pressure and friction on the skin, and avoid traumatic activity
  • During the first 2 to 4 weeks of treatment, avoid vigorous exercise and other activities that place stress mainly through friction on the hands and feet, including avoiding tight-fitting footwear as well as sandals, slippers or high heels
  • Consider wearing gloves or protective socks, if a potentially traumatic activity is planned
  • Advisable to wear gloves for doing manual labour (e.g. wash the dishes, cleaning, gardening etc.)
Dry skin and pruritus
  • Potential triggers for pruritus should be investigated in patient’s medical history together with a thorough clinical assessment
  • Advice with regards to moisturising should be provided, as well as for the use of moisturisers that are free of possible irritants
  • If pre-existing conditions are present, such as eczema the usual skin care should be intensified and for those with active rosacea, eczema or acne, a dermatologist should be consulted
  • Use tepid water, minimise showering and avoid soaps
  • Use topical emollients (fragranced or unfragranced) that are not too greasy
  • Use of moisturisers immediately after bathing may allow better hydration of the skin and avoid vigorous drying of the skin to minimise irritation
Nail changes (incl. paronychia)
  • Advice should be provided on preventive strategies including wearing comfortable shoes, putting on gloves while cleaning, 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
  • Patients should be educated regarding appropriate clipping of the nail plates, including avoidance of cutting the lateral margins of the nail plate shorter than the digit tip
  • Wear comfortable shoes, put on gloves while cleaning, keep hands dry as much as possible, minimising friction or pressure on the nail fold, avoid picking or manipulating of the nail, and apply petrolatum around the nails to retain moisture
  • Avoid cutting the lateral margins of the nail plate shorter than the digit tip
Stomatitis
  • Advice should be provided on keeping a good oral hygiene overall
  • An oral care plan should be developed before treatment and evaluated periodically, 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
  • Evaluate the use of dental appliances (e.g. dentures, braces etc.)
  • Practice keeping a good oral hygiene and effective dental care, and follow the dental plan discussed with the HCP
Photosensitivity
  • Patients should be alerted to the likelihood of photosensitivity
  • Advice should be provided with regards to protection measures including, regular application of sunscreen of a sun protection factor (SPF) of at least 30 (in some countries, SPF 50 is recommended) and wearing of protective clothing and hats when outside
  • Follow advice on regular application of sunscreen of a sun protection factor (SPF) of at least 30 (in some countries, SPF 50 is also recommended) and wearing of protective clothing and hats when outside
Keratoacanthomas and squamous cell carcinomas
  • Patients should be exhaustively examined 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
  • 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 excessive sun exposure
  • Patients should regularly monitor their skin to potentially allow earlier identification of these lesions
  • Avoid sun exposure and/ or ensure protective measures are taken against this stress factor

References

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  2. Komatsu H, et al., Eur J Oncol Nurs. 2019;38:65-69.
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  11. Lacouture ME, et al. Oncologist. 2008;13:1001–1011.
  12. Anderson R, et al. Oncologist. 2009;14:291–302.
  13. Gutzmer R, et al. Dtsch Arztebl Int. 2012;109:133–140.
  14. Autier J, et al. Arch Dermatol. 2008;144:886–892.
  15. Wood LS, et al. Commun Oncol. 2010;7:23–29.
  16. McLellan B, et al. Dermatol Ther. 2011;24:396–400.
  17. Potthoff K, et al. Ann Oncol. 2011;22:524–535.
  18. Kollmannsberger C, et al. Oncologist. 2011;16:543–553.
  19. Balagula Y, et al. J Support Oncol. 2010; 8:149–161.

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Last update: 13 September 2019