Pruritus | Multikinase Inhibitor Skin Toxicity

Pruritus linked to multikinase inhibitor treatment

Definition: Pruritus or itch associated with acneiform rash or xerosis.¹

Incidence: Pruritus is reported to be very common (>1/10) or common (≥1/100 to <1/10) in patients treated with multikinase inhibitors (cabozantinib, imatinib, sorafenib, sunitinib, dasatinib, pazopanib and vandetanib).^2-17

Grading and lesion characteristics: According to the CTCAEv5.0,¹⁸ pruritus is “A disorder characterised by an intense itching sensation”. Grading according to the CTCAEv5.0¹⁸ or to MESTT¹⁹ is quite similar.

Table 8: Grading of Pruritus According to the CTCAEv5.0

Grade	Description
1	Mild or localised; topical intervention indicated
2	Widespread and intermittent; skin changes from scratching (e.g. oedema, papulation, excoriations, lichenification, oozing/crusts); oral intervention indicated; limiting instrumental ADL
3	Widespread and constant; limiting self-care ADL or sleep; systemic corticosteroid or immunosuppressive therapy indicated

ADL: Activities of Daily Living

Table 9: Grading Pruritus According to MESTT

Grade	Description
1	Mild OR localised, intermittent, not requiring therapy
2	2A Moderate localised OR widespread intermittent AND requiring intervention 2B Moderate localised OR widespread constant AND requiring intervention
3	Severe, widespread constant AND interfering with sleep

Grade

Description

1

Mild OR localised, intermittent, not requiring therapy

2

2A Moderate localised OR widespread intermittent AND requiring intervention

2B Moderate localised OR widespread constant AND requiring intervention

3

Severe, widespread constant AND interfering with sleep

Onset: Pruritus onset usually occurs with the onset of xerosis or rash. Pruritus is often concurrent with rash as a manifestation of cutaneous inflammation and histamine release; and can begin early or later in the course of multikinase inhibitor therapy, depending on the kinetics and type of cutaneous reaction. Patients previously treated with other therapies may be more prone to developing pruritus and it is often associated with skin xerosis that can be successfully controlled with moisturisers.

Resolution: There are limited data in the literature regarding the resolution of pruritus following multikinase inhibitor therapy as a manifestation of skin inflammation; it usually responds to topical anti-inflammatory measures and moisturisers. Also see Prophylaxis and treatment - reactive management - skin changes – Pruritus.

Related Links

References

Lacouture ME, et al. Support Care Cancer. 2011;19:1079-1095.
European Medicines Agency. Cabometyx (cabozantinib) Summary of Product Characteristics 2019.
Food and Drug Administration. Cabometyx (cabozantinib) Prescribing Information 2019.
European Medicines Agency. Cometriq (cabozantinib) Summary of Product Characteristics 2019.
Food and Drug Administration. Cometriq (cabozantinib) Prescribing Information 2018.
European Medicines Agency. Glivec (imatinib) Summary of Product Characteristics 2019.
Food and Drug Administration. Gleevec (imatinib) Prescribing Information 2018.
European Medicines Agency. Nexavar (sorafenib) Summary of Product Characteristics 2018.
Food and Drug Administration. Nexavar (sorafenib) Prescribing Information 2018.
European Medicines Agency. Sutent (sunitinib) Summary of Product Characteristics 2019.
Food and Drug Administration. Sutent (sunitinib) Prescribing Information 2019.
European Medicines Agency. Sprycel (dasatinib) Summary of Product Characteristics 2019.
Food and Drug Administration. Sprycel (dasatinib) Prescribing Information 2018.
European Medicines Agency. Votrient (pazopanib) Summary of Product Characteristics 2018.
Food and Drug Administration. Votrient (pazopanib) Prescribing Information 2017.
European Medicines Agency. Caprelsa (vandetanib) Summary of Product Characteristics 2019.
Food and Drug Administration. Caprelsa (vandetanib) Prescribing Information 2018.
National Cancer Institute Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events and Common Toxicity Criteria [v5.0]. 27 November 2017. (Accessed 15 April 2019).
MASCC EGFR Inhibitor Skin Toxicity Tool (MESTT) (Accessed 15 April 2019).