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A case of intracranial hemorrhage caused by combined dabrafenib and trametinib therapy for metastatic melanoma.
Am J Case Rep. 2014 Oct 12; 15:441-3.AJ

Abstract

BACKGROUND

Combination therapy with BRAF V600E inhibitor dabrafenib and MEK inhibitor trametinib significantly improves progression-free survival of patients with BRAF V600-positive metastatic melanoma, but their use can be associated with life-threatening toxicities. We report the case of a patient receiving dabrafenib and trametinib for metastatic melanoma who developed intracranial hemorrhage while on therapy. Combination therapy with dabrafenib and trametinib improves progression-free survival of patients with BRAF V600-positive metastatic melanoma. Nevertheless, it is associated with an increased incidence and severity of any hemorrhagic event. To the best of our knowledge, this is the first report of intracranial hemorrhage with pathological confirmation.

CASE REPORT

We present the case of a 48-year-old man with metastatic melanoma of unknown primary site. He had metastases to the right clavicle, brain, liver, adrenal gland, and the right lower quadrant of the abdomen. He progressed on treatment with alpha-interferon. He was found to have a 4.5-cm mass in the left frontotemporal lobe and underwent gross total resection followed by adjuvant CyberKnife stereotactic irradiation. He was subsequently started on ipilimumab. Treatment was stopped due to kidney injury. He was then placed on dabrafenib and trametinib. He returned for follow-up complaining of severe headache and developed an episode of seizure. MRI showed a large area of edema at the left frontal lobe with midline shift. Emergency craniotomy was performed. Intracranial hemorrhage was found intra-operatively. Pathology from surgery did not find tumor cells, reported as organizing hemorrhage and necrosis with surrounding gliosis; immunohistochemistry for S100 and HMB45 were negative.

CONCLUSIONS

This case demonstrates the life-threatening adverse effects that can be seen with the newer targeted biological therapies. It is therefore crucial to maintain a high index of suspicion when patients on this combination therapy present with new neurologic symptoms.

Authors+Show Affiliations

Department of Internal Medicine, University of Miami, Miami, USA.Department of Hematology and Oncology, University of Miami, Miami, USA.Department of Pathology, University of Miami, Miami, USA.

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

25305754

Citation

Lee, Le Min, et al. "A Case of Intracranial Hemorrhage Caused By Combined Dabrafenib and Trametinib Therapy for Metastatic Melanoma." The American Journal of Case Reports, vol. 15, 2014, pp. 441-3.
Lee le M, Feun L, Tan Y. A case of intracranial hemorrhage caused by combined dabrafenib and trametinib therapy for metastatic melanoma. Am J Case Rep. 2014;15:441-3.
Lee, l. e. . M., Feun, L., & Tan, Y. (2014). A case of intracranial hemorrhage caused by combined dabrafenib and trametinib therapy for metastatic melanoma. The American Journal of Case Reports, 15, 441-3. https://doi.org/10.12659/AJCR.890875
Lee le M, Feun L, Tan Y. A Case of Intracranial Hemorrhage Caused By Combined Dabrafenib and Trametinib Therapy for Metastatic Melanoma. Am J Case Rep. 2014 Oct 12;15:441-3. PubMed PMID: 25305754.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A case of intracranial hemorrhage caused by combined dabrafenib and trametinib therapy for metastatic melanoma. AU - Lee,Le Min, AU - Feun,Lynn, AU - Tan,Yaohong, Y1 - 2014/10/12/ PY - 2014/10/13/entrez PY - 2014/10/13/pubmed PY - 2015/4/22/medline SP - 441 EP - 3 JF - The American journal of case reports JO - Am J Case Rep VL - 15 N2 - BACKGROUND: Combination therapy with BRAF V600E inhibitor dabrafenib and MEK inhibitor trametinib significantly improves progression-free survival of patients with BRAF V600-positive metastatic melanoma, but their use can be associated with life-threatening toxicities. We report the case of a patient receiving dabrafenib and trametinib for metastatic melanoma who developed intracranial hemorrhage while on therapy. Combination therapy with dabrafenib and trametinib improves progression-free survival of patients with BRAF V600-positive metastatic melanoma. Nevertheless, it is associated with an increased incidence and severity of any hemorrhagic event. To the best of our knowledge, this is the first report of intracranial hemorrhage with pathological confirmation. CASE REPORT: We present the case of a 48-year-old man with metastatic melanoma of unknown primary site. He had metastases to the right clavicle, brain, liver, adrenal gland, and the right lower quadrant of the abdomen. He progressed on treatment with alpha-interferon. He was found to have a 4.5-cm mass in the left frontotemporal lobe and underwent gross total resection followed by adjuvant CyberKnife stereotactic irradiation. He was subsequently started on ipilimumab. Treatment was stopped due to kidney injury. He was then placed on dabrafenib and trametinib. He returned for follow-up complaining of severe headache and developed an episode of seizure. MRI showed a large area of edema at the left frontal lobe with midline shift. Emergency craniotomy was performed. Intracranial hemorrhage was found intra-operatively. Pathology from surgery did not find tumor cells, reported as organizing hemorrhage and necrosis with surrounding gliosis; immunohistochemistry for S100 and HMB45 were negative. CONCLUSIONS: This case demonstrates the life-threatening adverse effects that can be seen with the newer targeted biological therapies. It is therefore crucial to maintain a high index of suspicion when patients on this combination therapy present with new neurologic symptoms. SN - 1941-5923 UR - https://www.unboundmedicine.com/medline/citation/25305754/A_case_of_intracranial_hemorrhage_caused_by_combined_dabrafenib_and_trametinib_therapy_for_metastatic_melanoma_ L2 - https://www.amjcaserep.com/download/index/idArt/890875 DB - PRIME DP - Unbound Medicine ER -