Crizotinib-associated toxic epidermal necrolysis in an ALK-positive advanced NSCLC patient

Abstract

Abstract.Crizotinib is an oral small-molecule inhibitor of anaplastic lymphoma kinase (ALK) tyrosine-kinase that has been approved for treating patients with advanced echinoderm microtubule associated protein like 4-ALK rearranged non-small-cell lung cancer (NSCLC). Toxic epidermal necrolysis (TEN) is a rare adverse event associated with crizotinib. The present study reported a case of a 75-year-old Chinese male patient with advanced NSCLC with ALK fusion, who developed TEN after 56 days of crizotinib treatment and demised due to this dermatological adverse event. The occurrence of severe cutaneous necrolysis that predominantly involves the skin and mucous membranes during crizotinib treatment should alert clinicians to be aware of TEN and take prompt actions.

Potentially life‑threatening severe cutaneous adverse reactions associated with tyrosine kinase inhibitors (Review)

“…Since then, additional drugs within this class have been approved including alectinib, ceritinib, and brigatinib (38). While these agents are rarely associated with severe cutaneous toxicities, they have been linked to erythema multiforme (39) and TEN (40).…”

“…Stevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) has been associated with EGFR inhibitors (54,(62)(63)(64)(65)(66)(67)(68)(69)(70), BRAF inhibitors (71-78), bcr-abl/c-KIT/PDGFR inhibitors (79,80), ALK inhibitors (40), and MKIs (52)(53)(54). Drug reaction with eosinophilia and systemic symptoms (DRESS) has been associated with BRAF inhibitors (71,(81)(82)(83)(84)(85), bcr-abl/ c-KIT/PDGFR inhibitors (86-91), HER-2 inhibitors (92), and MKIs (56).…”

Conceptual frameworks of synthetic lethality in clear cell carcinoma of the ovary (Review)

“…Specific inhibitors of the cancer driver genes or oncogenes may contribute to development of idiosyncratic toxicity (23). An example of synthetic lethality is PARP inhibition in BRCA1/2-deficient ovarian and/or breast cancer types (3,24,25).…”

Postmarketing safety of anaplastic lymphoma kinase (ALK) inhibitors: an analysis of the FDA Adverse Event Reporting System (FAERS)

“…11 Treatment with ALK inhibitors is usually well tolerated; however, there are common class adverse events such as nausea, vomiting, diarrhea, pneumonitis, and cardiac toxicity. 12 Some less common adverse events have been reported as well including rectal perforation, 13 cataract, macular edema or blindness, 14,15 osteitis, 16 ventricular fibrillation, 17,18 pulmonary arterial hypertension, 19 pancreatitis, 20 cholestasis, 21 alopecia, 22 proteinuria, 23 myasthenia gravis, 24 toxic epidermal necrolysis, 25 sarcoid-like reaction, 26 and photosensitivity. 27 Treatment discontinuation due to adverse events among different ALK inhibitors were as follow: 12% with crizotinib as in the PROFILE 1014 trial, 28 5% with ceritinib as in the ASCEND 4 trial, 29 11% with alectinib as in the ALEX trial, 30 12% with brigatinib as in the ALTA-1L trial, 10 and 7% with lorlatinib as in the CROWN trial.…”

“…Treatment with ALK inhibitors is usually well tolerated; however, there are common class adverse events such as nausea, vomiting, diarrhea, pneumonitis, and cardiac toxicity. 12 Some less common adverse events have been reported as well including rectal perforation, 13 cataract, macular edema or blindness, 14 , 15 osteitis, 16 ventricular fibrillation, 17 , 18 pulmonary arterial hypertension, 19 pancreatitis, 20 cholestasis, 21 alopecia, 22 proteinuria, 23 myasthenia gravis, 24 toxic epidermal necrolysis, 25 sarcoid-like reaction, 26 and photosensitivity. 27 …”