Reactions 1704, p131 - 2 Jun 2018
Various toxicities including first report of acute
intraventricular conduction disorder: case report
An 86-year-old woman developed maculopapular eruption,
elevated aspartate aminotransferase level, elevated alanine
aminotransferase level, elevated alkaline phosphatase level
and acute intraventricular conduction disorder during
treatment with dabrafenib and trametinib [routes not stated].
The woman was diagnosed with metastatic melanoma and
was detected to have a BRAF V600E mutation. She started
receiving treatment with dabrafenib 150mg twice daily and
trametinib 2mg daily. After 16 days of the treatment initiation,
she developed grade 2 maculopapular eruption and grade 3
elevation of aspartate aminotransferase level, grade 2 elevation
of alanine aminotransferase level and grade 2 elevation of
alkaline phosphatase level.
The woman’s drugs were replaced by prednisolone. After
her condition improved, prednisolone dose was reduced and
she was restarted on low doses of dabrafenib 100mg twice
daily and trametinib 1.5mg daily. Five hours later, she
complained of chills, and her BP was 73/50mm Hg with a heart
rate of 114 beats/minute. An ECG demonstrated a widened
QRS complex by 136ms. Ischaemic heart disease was ruled
out based on echocardiographic findings. Acute
intraventricular conduction disorder was suspected.
Dabrafenib and trametinib were discontinued, and she was
started on rehydration. After 3 days, her vital signs and ECG
findings returned to normal.
On day 9, low doses of dabrafenib 75mg twice daily and
trametinib 1.0mg daily were restarted. After 4 hours, she again
experienced widening of the QRS complex and decreased BP.
Dabrafenib and trametinib were stopped, after which
normalisation of anomalous QRS complex and BP was
Author comment: "While dabrafenib and trametinib
combination therapy improved the overall survival of patients
with BRAF mutant metastatic melanoma treatment-related
adverse events are a major problem. Ours is the first
documentation of progressive intraventricular conduction
disorder (IVCD) demonstrated electrocardiographically (ECG)
as a widened QRS complex."
Yamamura K, et al. Acute intraventricular conduction disorder due to combination
therapy with dabrafenib and trametinib for metastatic melanoma: Case report.
Journal of Dermatology 45: e120-e121, No. 5, May 2018. Available from: URL:
http://doi.org/10.1111/1346-8138.14148 - Japan
Editorial comment: A search of AdisBase, Medline, Embase
and the WHO ADR database did not reveal any previous case
reports of acute intraventricular conduction disorder associated
Reactions 2 Jun 2018 No. 17040114-9954/18/1704-0001/$14.95 Adis © 2018 Springer International Publishing AG. All rights reserved