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Melanoma brain metastases and vemurafenib: need for further investigation.

Abstract
Brain metastases are a major cause of morbidity and mortality in patients with advanced melanoma. With the development of targeted agents for the treatment of metastatic melanoma, a great deal of interest has focused on whether selective BRAF inhibitors may play a role in the treatment of brain metastases in lieu of or in addition to surgery and/or radiation therapy. However, relatively little is known about the intracranial effectiveness of vemurafenib, the only US Food and Drug Administration-approved selective BRAF V600E inhibitor, because patients with brain metastases have historically been excluded from vemurafenib clinical trials. We describe 3 patients with BRAF V600E mutation metastatic melanoma in whom treatment with vemurafenib resulted in prompt extracranial disease response but progression of metastatic disease in the brain. Further, we discuss possible mechanisms responsible for the suboptimal central nervous system response observed in these patients and alternative therapies for patients with melanoma metastatic to the brain.
AuthorsNicole M Rochet, Roxana S Dronca, Lisa A Kottschade, Rahul N Chavan, Brian Gorman, Julie R Gilbertson, Svetomir N Markovic
JournalMayo Clinic proceedings (Mayo Clin Proc) Vol. 87 Issue 10 Pg. 976-81 (Oct 2012) ISSN: 1942-5546 [Electronic] England
PMID23036672 (Publication Type: Case Reports, Journal Article)
CopyrightCopyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Indoles
  • Sulfonamides
  • Vemurafenib
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
Topics
  • Adult
  • Brain Neoplasms (drug therapy, genetics, pathology, secondary)
  • Disease Progression
  • Fatal Outcome
  • Female
  • Humans
  • Indoles (therapeutic use)
  • Male
  • Melanoma (drug therapy, genetics, secondary)
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins B-raf (antagonists & inhibitors, genetics)
  • Skin Neoplasms (drug therapy, genetics, pathology)
  • Sulfonamides (therapeutic use)
  • Vemurafenib

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