Necrotizing Vasculitis Triggered by Gefitinib: An Unusual Clinical Presentation

Ko, Jui‐Hung; Shih, Yi-Chin; Hui, Rosaline Chung‐Yee; Yang, Chih-Hsun

doi:10.1200/jco.2010.31.8352

Cited by 8 publications

(7 citation statements)

References 6 publications

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“…However, these drugs may cause a range of cutaneous reactions, such as acneiform rash, pruritus, paronychia, and xeroderma . In addition to common papulopustular reactions, there have also been several reports of EGFR‐TKIs being associated with vascular adverse events, namely, purpuric drug eruptions , leukocytoclastic vasculitis , livedo reticularis with retiform purpura , and purpura with petechiae . These conditions might belong to a spectrum of a single disorder.…”

Section: Introductionmentioning

confidence: 99%

Purpuric drug eruptions induced by EGFR tyrosine kinase inhibitors are associated with IQGAP1‐mediated increase in vascular permeability

Sheen

Lin

Tzeng

et al. 2020

The Journal of Pathology

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Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) are used as a treatment for non‐small‐cell lung cancer. There have been some reports of EGFR‐TKIs being associated with vascular adverse events. We found that EGFR‐TKIs decreased the proliferation of HMEC‐1s (immortalized human dermal microvascular endothelial cells) and HMVECs (human dermal microvascular endothelial cells), and also inhibited the phosphorylation of EGFR and ERK. We examined the mRNA expression profile of erlotinib‐treated HMEC‐1s and identified IQ motif containing GTPase activating protein 1 (IQGAP1) as the most consistently up‐regulated transcript and protein. IQGAP1 was also overexpressed and co‐localized with endothelial cells in the lesional skin. Notably, increased IQGAP1 expression was associated with decreased transendothelial electrical resistance and increased vascular permeability in vitro. Erlotinib treatment enriched the staining of IQGAP1 and reduced the intensities of α‐catenin at the sites of cell–cell contact. In conclusion, erlotinib induces adherens junction dysfunction by modulating the expression of IQGAP1 in dermal endothelial cells. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Introductionmentioning

confidence: 99%

Purpuric drug eruptions induced by EGFR tyrosine kinase inhibitors are associated with IQGAP1‐mediated increase in vascular permeability

Sheen

Lin

Tzeng

et al. 2020

The Journal of Pathology

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“…Interestingly, in several cases, rechallenge with reduced‐dose erlotinib and osimertinib did not induce further leucocytoclastic vasculitis 3,4 . However, recurrence of symptoms did occur in one case following rechallenge with gefitinib, 5 and likewise with cabozantinib in our case. Notably, our patient has since been treated for > 4 months with axitinib, another TKI with a different kinase specificity, which has resulted in radiological response and no treatment‐related toxicity.…”

Section: Figurementioning

confidence: 49%

Cutaneous leucocytoclastic vasculitis secondary to cabozantinib therapy for renal cell carcinoma

Coltart

Sutton²,

Roche

et al. 2021

Clin Exp Dermatol

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“…[85][86][87] The most serious AE observed with gefitinib is pulmonary toxicity, including interstitial lung disease, which may be fatal. 88 Indeed, gefitinib-associated skin reactions correlate with an increased likelihood of tumor response and symptomatic improvement, although durable tumor regression has also been observed in patients with mild forms of rash. 85 The most common skin AEs of gefitinib are acneiform eruptions, xerosis, and paronychia, most of which can be attributed to the specific inhibition of cutaneous EGFR by gefitinib.…”

Section: Adverse Effectsmentioning

confidence: 99%

Clinical Pharmacokinetics of Tyrosine Kinase Inhibitors

Josephs

Fisher

Spicer

et al. 2013

Therapeutic Drug Monitoring

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The treatment of many malignancies has been improved in recent years by the introduction of molecular targeted therapies. These drugs interact preferentially with specific targets that are mutated and/or overexpressed in malignant cells. A group of such targets are the tyrosine kinases, against which a number of inhibitors (tyrosine kinase inhibitors, TKIs) have been developed. Imatinib, a TKI with targets that include the breakpoint cluster region-Abelson (bcr-abl) fusion protein kinase and mast/stem cell growth factor receptor kinase (c-Kit), was the first clinically successful drug of this type and revolutionized the treatment and prognosis of chronic myeloid leukemia and gastrointestinal stromal tumors. This success paved the way for the development of other TKIs for the treatment of a range of hematological malignancies and solid tumors. To date, 14 TKIs have been approved for clinical use and many more are under investigation. All these agents are given orally and are substrates of a range of drug transporters and metabolizing enzymes. In addition, some TKIs are capable of inhibiting their own transporters and metabolizing enzymes, making their disposition and metabolism at steady-state unpredictable. A given dose can therefore give rise to markedly different plasma concentrations in different patients, favoring the selection of resistant clones in the case of subtherapeutic exposure, and increasing the risk of toxicity if dosage is excessive. The aim of this review was to summarize current knowledge of the clinical pharmacokinetics and known adverse effects of the TKIs that are available for clinical use and to provide practical guidance on the implications of these data in patient management, in particular with respect to therapeutic drug monitoring.

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Necrotizing Vasculitis Triggered by Gefitinib: An Unusual Clinical Presentation

Cited by 8 publications

References 6 publications

Purpuric drug eruptions induced by EGFR tyrosine kinase inhibitors are associated with IQGAP1‐mediated increase in vascular permeability

Purpuric drug eruptions induced by EGFR tyrosine kinase inhibitors are associated with IQGAP1‐mediated increase in vascular permeability

Cutaneous leucocytoclastic vasculitis secondary to cabozantinib therapy for renal cell carcinoma

Clinical Pharmacokinetics of Tyrosine Kinase Inhibitors

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