PMID- 25014231
OWN - NLM
STAT- MEDLINE
DCOM- 20150313
LR  - 20140819
IS  - 1744-764X (Electronic)
IS  - 1474-0338 (Linking)
VI  - 13
IP  - 9
DP  - 2014 Sep
TI  - Dabrafenib for the treatment of BRAF V600-positive melanoma: a safety evaluation.
PG  - 1249-58
LID - 10.1517/14740338.2014.939954 [doi]
AB  - INTRODUCTION: V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitors 
      are emerging as the standard of care for treating advanced melanomas harboring 
      the BRAF V600 oncogenic mutation. Dabrafenib is the second approved selective 
      BRAF inhibitor (after vemurafenib) for the treatment of unresectable or 
      metastatic BRAF V600-positive melanoma. AREAS COVERED: This review covers the 
      current data on the efficacy and safety of the selective BRAF inhibitor 
      dabrafenib in patients with metastatic BRAF V600 positive melanoma. The 
      pharmacological, safety and efficacy data are discussed from Phase I, II, and III 
      studies of dabrafenib monotherapy as well as in combination with the MEK 
      inhibitor trametinib. EXPERT OPINION: Dabrafenib has demonstrated comparable 
      efficacy to vemurafenib in BRAF V600E mutant melanoma patients. Dabrafenib is 
      well tolerated in patients with metastatic melanoma, including patients with 
      brain metastases. Nevertheless side effects are common, but usually manageable. 
      In the Phase III study testing dabrafenib, 53% of patients reported grade 2 or 
      higher adverse events (AEs). Toxicities were similar to those seen in the 
      early-phase trials, with the most common being cutaneous manifestations 
      (hyperkeratosis, papillomas, palmar-plantar erythrodysesthesia), pyrexia, 
      fatigue, headache, and arthralgia. Combining a BRAF inhibitor with a MEK 
      inhibitor, which may block paradoxical MAPK activation in BRAF wild type (skin) 
      cells, may lower the incidence of squamoproliferative eruptions.
FAU - Rutkowski, Piotr
AU  - Rutkowski P
AD  - Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 
      Department of Soft Tissue/Bone Sarcoma and Melanoma , Roentgena 5, 02-781 Warsaw 
      , Poland +48 22 6439375 ; +48 22 6439791 ; rutkowskip@coi.waw.pl.
FAU - Blank, Christian
AU  - Blank C
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20140711
PL  - England
TA  - Expert Opin Drug Saf
JT  - Expert opinion on drug safety
JID - 101163027
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Imidazoles)
RN  - 0 (Oximes)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridones)
RN  - 0 (Pyrimidinones)
RN  - 33E86K87QN (trametinib)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
RN  - QGP4HA4G1B (dabrafenib)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage/adverse effects/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse 
      effects/therapeutic use
MH  - Humans
MH  - Imidazoles/administration & dosage/adverse effects/*therapeutic use
MH  - Melanoma/*drug therapy/genetics/pathology
MH  - Mutation
MH  - Neoplasm Metastasis
MH  - Oximes/administration & dosage/adverse effects/*therapeutic use
MH  - Protein Kinase Inhibitors/administration & dosage/adverse effects/therapeutic use
MH  - Proto-Oncogene Proteins B-raf/genetics
MH  - Pyridones/administration & dosage
MH  - Pyrimidinones/administration & dosage
MH  - Skin Neoplasms/*drug therapy/genetics/pathology
OTO - NOTNLM
OT  - adverse events
OT  - dabrafenib
OT  - melanoma
OT  - v-raf murine sarcoma viral oncogene homolog B1 inhibitor
EDAT- 2014/07/12 06:00
MHDA- 2015/03/17 06:00
CRDT- 2014/07/12 06:00
PHST- 2014/07/12 06:00 [entrez]
PHST- 2014/07/12 06:00 [pubmed]
PHST- 2015/03/17 06:00 [medline]
AID - 10.1517/14740338.2014.939954 [doi]
PST - ppublish
SO  - Expert Opin Drug Saf. 2014 Sep;13(9):1249-58. doi: 10.1517/14740338.2014.939954. 
      Epub 2014 Jul 11.