Cardiac toxicity of combined vemurafenib and cobimetinib administration
| Autor: | Mariapina Gallo, Georgios Eleftheriou, Laura Trevisani, Mauro Gori, Filippo Taddei, Roberto Fiocchi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
050101 languages & linguistics
medicine.medical_specialty Torsades de pointes 02 engineering and technology QT interval Sudden cardiac death chemistry.chemical_compound Piperidines Internal medicine 0202 electrical engineering electronic engineering information engineering medicine Humans 0501 psychology and cognitive sciences Pharmacology (medical) cardiovascular diseases Vemurafenib Melanoma Pharmacology Cobimetinib Ejection fraction business.industry 05 social sciences Middle Aged medicine.disease Cardiotoxicity chemistry Heart failure Ventricular fibrillation cardiovascular system Cardiology Azetidines 020201 artificial intelligence & image processing Female Neoplasm Recurrence Local business medicine.drug |
| Zdroj: | International journal of clinical pharmacology and therapeutics. 57(5) |
| ISSN: | 0946-1965 |
| Popis: | Vemurafenib and cobimetinib are extremely effective in treating V600E-mutated metastatic melanoma, but their use is associated with toxic cardiac effects. Vemurafenib-induced prolonged QTc interval may be associated with ventricular fibrillation and sudden cardiac death. Cobimetinib-induced myocardial damage may lead to severely reduced heart function and lethal heart failure. Few data are available about the time course of recovery after these side effects. We provide the first description of cardiac recovery after potentially fatal cardiac side effects due to vemurafenib and cobimetinib administration. A 51-year-old woman was admitted to our hospital with diarrhea, vomiting, and asthenia. At admission, her left ventricular ejection fraction (LVEF) was severely reduced and QTc interval was extremely elongated (normal range QTc ≤ 440 ms). Blood levels of troponin I (normal values below 0.07 ng/mL) and brain natriuretic peptide (brain natriuretic peptide (BNP), normal range l 100 pg/mL) were elevated. During hospitalization, she developed recurrent runs of torsades de pointes degenerating into ventricular fibrillation, requiring direct current electric shock (DC shocks). Vemurafenib and cobimetinib were discontinued. Three weeks later, QTc was still higher than 500 ms and LVEF lower than 30%: an implantable cardioverter-defibrillator (ICD) was implanted. Myocardial function improved within 1 month, and QTc intervals became 500 ms 1 week later. After 6 months, a normal ejection fraction (> 55%) was observed, and the QTc interval was 455 ms. The patient died rather from metastatic melanoma recurrence 8 months later. This case report highlights the time-course of recovery after combined vemurafenib-cobimetinib-induced severe myocardial damage. Further research is warranted to assess whether and how antineoplastic therapy may be resumed after QT normalization and heart function recovery. . |
| Databáze: | OpenAIRE |
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