From the Guidelines
Tyrosine Kinase Inhibitors (TKIs) are associated with a range of side effects, including skin toxicity, oral mucositis, diarrhea, endocrine dysfunction, and liver problems, with the most common adverse effect being skin toxicity, usually manifested as acneiform rash, skin fissure, xerosis, and paronychia, as reported in the 2022 study 1. The side effects of TKIs can be managed with supportive care, including topical and systemic corticosteroids, antibiotics, and oral isotretinoin. Patients who develop pruritus may benefit from H1-antihistamines or gamma-aminobutterc agonists such as gabapentin. Key points to consider when managing TKI side effects include:
- The severity of cutaneous side effects is dose-related, but most of them are mild to moderate and self-limiting, as noted in the 2016 study 1.
- Mild to moderate adverse events can be managed with topical therapies, systemic therapies with antihistamines, or short courses of systemic steroids.
- Severe cases always require interruption or temporary reduction of TKI, and rare cases of very severe skin reactions require the permanent withdrawal of the causative TKI.
- Regular monitoring of liver function tests is essential, as TKIs can cause hepatotoxicity, and some TKIs also cause specific side effects, such as dasatinib causing pleural effusions, nilotinib increasing cardiovascular risk, and pazopanib causing hypertension, as discussed in the context of TKI therapy 1.
From the Research
Side Effects of Tyrosine Kinase Inhibitors (TKI)
- TKIs cause a variety of side effects in nearly all treated patients, including:
- Hypertension
- Gastrointestinal disturbances (diarrhea, abdominal pain, nausea, vomiting)
- Skin reactions (rashes, acne, hand-foot syndrome)
- Fatigue
- Weight loss 2
- Most side effects are mild and moderate and manageable by dose adjustment and concomitant therapy, however, some complications may be life-threatening or even fatal 2
- Skin toxicity, including folliculitis, is a common side effect of TKIs, occurring in more than 50% of patients 3
- Other common side effects of TKIs include:
- Cardiovascular toxicities, including hypertension, atrial fibrillation, reduced cardiac function, and heart failure, are also reported with TKIs 4, 5
- TKIs may also cause endocrine adverse effects, such as hypercholesterolemia and hypertriglyceridemia, and thyroid dysfunction 4
- Dermatological and gastrointestinal adverse effects, including skin toxicity and diarrhea, are also common with TKIs 4, 5
- The occurrence and management of side effects may differ between different TKIs, with second-generation TKIs reducing the incidence of most side effects reported with imatinib 6