PMID- 26109403
OWN - NLM
STAT- MEDLINE
DCOM- 20160913
LR  - 20220316
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 173
IP  - 4
DP  - 2015 Oct
TI  - Cutaneous toxicities associated with vemurafenib therapy in 107 patients with 
      BRAF V600E mutation-positive metastatic melanoma, including recognition and 
      management of rare presentations.
PG  - 1024-31
LID - 10.1111/bjd.13958 [doi]
AB  - BACKGROUND: Vemurafenib significantly improved overall survival compared with 
      dacarbazine in patients with metastatic or unresectable BRAF V600E-positive 
      melanoma in the BRIM-3 trial. However, vemurafenib was associated with a number 
      of skin-related adverse events (AEs). OBJECTIVES: To investigate the incidence 
      and management of vemurafenib-associated skin AEs. METHODS: This retrospective, 
      observational study included adult patients with stage IIIC or IV melanoma who 
      received vemurafenib between March 2010 and August 2013. Patients received oral 
      vemurafenib 960 mg twice daily, with dose interruptions and reductions allowed 
      for AE management. RESULTS: In total 107 patients were treated with vemurafenib 
      during the study period. The most frequent clinically important skin-related AEs 
      were rash (64%), squamoproliferative growths (41%), photosensitivity (40%) and 
      squamous cell carcinoma (SCC) or keratoacanthoma (KA; 20%). Rare cases of 
      granulomatous dermatitis and cutaneous T-cell lymphoma were also found. Rash was 
      manageable with corticosteroids and dose modifications; squamoproliferative 
      growths and SCCs/KAs were treated with cryotherapy and surgical excision, 
      respectively. Patients were counselled regarding phototoxicity. The uncontrolled 
      nature and retrospective design of the study, and the small patient numbers are 
      limitations. CONCLUSIONS: Vemurafenib appears to have a predictable and 
      manageable AE profile. Proactive management can limit the impact of AEs on 
      patients, allowing treatment to continue despite toxicities.
CI  - (c) 2015 British Association of Dermatologists.
FAU - Sinha, R
AU  - Sinha R
AD  - Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, U.K.
AD  - Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, U.K.
FAU - Larkin, J
AU  - Larkin J
AD  - Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, U.K.
FAU - Gore, M
AU  - Gore M
AD  - Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, U.K.
FAU - Fearfield, L
AU  - Fearfield L
AD  - Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, U.K.
AD  - Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, U.K.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20151011
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (Indoles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Sulfonamides)
RN  - 207SMY3FQT (Vemurafenib)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
SB  - IM
CIN - Br J Dermatol. 2015 Oct;173(4):892-3. PMID: 26511828
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Squamous Cell/chemically induced
MH  - Drug Eruptions/*etiology/pathology/therapy
MH  - Exanthema/genetics
MH  - Female
MH  - Humans
MH  - Indoles/administration & dosage/*adverse effects
MH  - Keratoacanthoma/chemically induced
MH  - Lymphoma, T-Cell, Cutaneous/chemically induced
MH  - Male
MH  - Melanoma/*drug therapy/genetics
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Photosensitivity Disorders/chemically induced
MH  - Protein Kinase Inhibitors/administration & dosage/*adverse effects
MH  - Proto-Oncogene Proteins B-raf/antagonists & inhibitors/genetics
MH  - Retrospective Studies
MH  - Skin Neoplasms/*drug therapy/genetics
MH  - Sulfonamides/administration & dosage/*adverse effects
MH  - Vemurafenib
MH  - Young Adult
EDAT- 2015/06/26 06:00
MHDA- 2016/09/14 06:00
CRDT- 2015/06/26 06:00
PHST- 2015/05/27 00:00 [accepted]
PHST- 2015/06/26 06:00 [entrez]
PHST- 2015/06/26 06:00 [pubmed]
PHST- 2016/09/14 06:00 [medline]
AID - 10.1111/bjd.13958 [doi]
PST - ppublish
SO  - Br J Dermatol. 2015 Oct;173(4):1024-31. doi: 10.1111/bjd.13958. Epub 2015 Oct 11.