Background: Tyrosine kinase inhibitors (TKIs) are crucial to treating endocrine-related malignancies, including advanced thyroid cancers and neuroendocrine tumors, but their benefit is tempered by cutaneous adverse events (CAEs) that impair adherence and quality of life. Objective: To summarize the dermatologic toxicities of TKIs used in endocrine oncology and provide practical, multidisciplinary guidance for prevention and management. Methods: Narrative synthesis of clinical trial reports, post-marketing studies, and specialty guidelines pertinent to lenvatinib, vandetanib, cabozantinib, and other commonly used TKIs, integrating dermatologic and endocrine perspectives on mechanisms and care pathways. Results: VEGFR-targeted TKIs frequently cause hand–foot skin reaction, xerosis, fissuring, paronychia, and impaired wound healing; multikinase inhibition also produces alopecia, pigmentary changes, and mucositis. Epidermal growth factor receptor (EGFR) and rearranged during transfection (RET) inhibition with vandetanib is associated with acneiform eruption, photosensitivity, and nail fragility. Pathogenesis reflects on-target inhibition of VEGF/EGFR signaling leading to keratinocyte dysfunction, vascular fragility, and altered eccrine mechanics. Early risk stratification, patient education, and bundle-based prophylaxis (emollients, keratolytics, urea-based creams, sun protection) reduce incidence and severity. Grade-based algorithms combining topical corticosteroids/antibiotics, dose interruptions or reductions, and short systemic courses (e.g., doxycycline, antihistamines) enable symptom control while maintaining anticancer intensity. Close coordination around procedures minimizes wound-healing complications. Conclusions: Dermatologic toxicities are predictable, mechanism-linked, and manageable with proactive, multidisciplinary care. Standardized prevention and treatment pathways tailored to specific TKIs—particularly lenvatinib, vandetanib, and cabozantinib—can preserve dose intensity, optimize quality of life, and sustain antineoplastic efficacy.
Cutaneous Adverse Events of Tyrosine Kinase Inhibitors in Endocrine Tumors: Clinical Features, Mechanisms, and Management Strategies
Rosset, Francois;Nervo, Alice;Piovesan, Alessandro;Pala, Valentina;Vaccaro, Elisa;Mastorino, Luca;Arvat, Emanuela
2025-01-01
Abstract
Background: Tyrosine kinase inhibitors (TKIs) are crucial to treating endocrine-related malignancies, including advanced thyroid cancers and neuroendocrine tumors, but their benefit is tempered by cutaneous adverse events (CAEs) that impair adherence and quality of life. Objective: To summarize the dermatologic toxicities of TKIs used in endocrine oncology and provide practical, multidisciplinary guidance for prevention and management. Methods: Narrative synthesis of clinical trial reports, post-marketing studies, and specialty guidelines pertinent to lenvatinib, vandetanib, cabozantinib, and other commonly used TKIs, integrating dermatologic and endocrine perspectives on mechanisms and care pathways. Results: VEGFR-targeted TKIs frequently cause hand–foot skin reaction, xerosis, fissuring, paronychia, and impaired wound healing; multikinase inhibition also produces alopecia, pigmentary changes, and mucositis. Epidermal growth factor receptor (EGFR) and rearranged during transfection (RET) inhibition with vandetanib is associated with acneiform eruption, photosensitivity, and nail fragility. Pathogenesis reflects on-target inhibition of VEGF/EGFR signaling leading to keratinocyte dysfunction, vascular fragility, and altered eccrine mechanics. Early risk stratification, patient education, and bundle-based prophylaxis (emollients, keratolytics, urea-based creams, sun protection) reduce incidence and severity. Grade-based algorithms combining topical corticosteroids/antibiotics, dose interruptions or reductions, and short systemic courses (e.g., doxycycline, antihistamines) enable symptom control while maintaining anticancer intensity. Close coordination around procedures minimizes wound-healing complications. Conclusions: Dermatologic toxicities are predictable, mechanism-linked, and manageable with proactive, multidisciplinary care. Standardized prevention and treatment pathways tailored to specific TKIs—particularly lenvatinib, vandetanib, and cabozantinib—can preserve dose intensity, optimize quality of life, and sustain antineoplastic efficacy.
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