Extreme elevation of acute phase reactants and shock secondary to dabrafenib–trametinib

Abstract

The emerging role of BRAF and MEK tyrosine-kinase inhibitors has shown new opportunities of treatment for patients with advanced melanoma and BRAF mutations. Its use is associated with some toxicities, as pyrexia, that clinicians may not be familiarized with. We present the case of a patient diagnosed with stage IV melanoma BRAF Val600E mutated who was started on dabrafenib and trametinib and developed three severe episodes of fever, hypotension and acute phase reactants elevation during the first 3 months of therapy, in the absence of microbiological demonstration of infection. The episodes were initially managed as a septic shock with broadspectrum antibiotics and vasoactive drugs, while treatment with dabrafenib and trametinib was withheld. After two subsequent dose reduction of dabrafenib, the patient did not experience new episodes of fever. Melanoma Res 31: 268

Cerebral infarction after treatment with dabrafenib plus trametinib for BRAF‐V600E‐positive non–small cell lung cancer: A case report

“…Immediately thereafter, paralysis occurred, suggesting that hemoconcentration caused by intravascular dehydration because of high fever may have caused the CI. Although not reported in clinical trials, there has been one report of fever and hypotension in cases of melanoma 5 . As is well known, CI is a common disease and the CI might have occurred by chance, or the sequelae of DIC or steroid use might have influenced the onset of CI.…”

“…Although not reported in clinical trials, there has been one report of fever and hypotension in cases of melanoma. 5 As is well known, CI is a common disease and the CI might have occurred by chance, or the sequelae of DIC or steroid use might have influenced the onset of CI. However, the pyrexia and hypotension immediately after administration occurred and then CI occurred.…”