Case series of dabrafenib-trametinib-induced pyrexia successfully treated with colchicine
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The most common adverse event (AE) of dabrafenib and trametinib (DT) is pyrexia, which has been reported to occur in up to 71% of patients. Pyrexia resulted in therapy discontinuation in up to 26% of patients that otherwise were benefiting from the treatment. Little is known about the pathogenesis and optimal management of this common AE. We hypothesized that the etiology of pyrexia in patients treated with DT could be extrapolated from DT-related cutaneous adverse effects in which a paradoxical MAPK pathway activation has been identified. Based on preliminary data by our group suggesting an upregulation of the mitogen-activated protein kinases (MAPKs) in human lymphocytes exposed to dabrafenib and trametinib, specifically elevated expression of phosphorylated JNK (p-JNK), p38 MAPK (p-p38 MAPK), and ERK5 (p-ERK5), we hypothesized that the mechanism of MAPK pathway activation with DT therapy is similar to that reported in patients with familial Mediterranean fever (FMF), a rare, inherited condition characterized by episodes of fever and rash that responds exceedingly well to colchicine-based therapy in which the MAPK pathway is hyper-activated. Based on this association, our group explored the use of oral colchicine for the treatment of DT-associated pyrexia in five patients with metastatic melanoma.
KeywordsPyrexia Dabrafenib Trametinib MAPK pathway Colchicine
We acknowledge the Melanoma Care Team in the Division of Medical Oncology at Mayo Clinic Rochester for providing excellent patient care and supporting this research project. We also acknowledge Dr. Anagha Bangalore Kumar and Courtney L. Erskine for their technical support and our research coordinator Renee Bradshaw and Heidi Turner for their research support.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest, the authors have full control of the data; we agree to allow the journal to review their data if requested.
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