CONCISE COMMUNICATION
BJD
British Journal of Dermatology
Systemic retinoids for the chemoprevention of cutaneous
squamous cell carcinoma and verrucal keratosis in a cohort
of patients on BRAF inhibitors
R. Anforth,
1,2
T.C.M.P. Blumetti,
1
A. Clements,
2,3
R. Kefford,
2,3,4
G.V. Long
2,3,4
and P. Fernandez-Pe~ nas
1,2
1
Department of Dermatology(D5a) and
3
Westmead Institute for Cancer Research, Westmead Hospital, Sydney, NSW 2145, Australia
2
Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
4
Melanoma Institute Australia, Sydney, NSW, Australia
Correspondence
Rachael Anforth.
E-mail: rachael.anforth@sydney.edu.au
Accepted for publication
15 July 2013
Funding source
This study was supported in part by Epiderm,
Australia (P.F.-P. and R.A.). Melanoma Institute
Australia receives funding from Roche.
Conflicts of interest
P.F.-P. has acted as a consultant or in an advisory
role for Roche; G.V.L. has acted as a consultant or
in an advisory role for Roche, Amgen, Bristol-
Myers Squibb, GlaxoSmithKline (GSK) and Novar-
tis. R.K. has received honoraria from GSK and
Roche, and other remuneration from GSK.
DOI 10.1111/bjd.12519
Summary
Background The treatment of metastatic melanoma has changed greatly with the
development of inhibitors targeted at the mutated BRAF kinase present in up to 50%
of metastatic melanoma cases. These agents, vemurafenib and dabrafenib, have been
shown to increase median survival. Unfortunately, they have also been associated
with the development of verrucal keratosis (VK) and cutaneous squamous cell carci-
noma (cuSCC). These lesions require surgical excision, and when a large number of
these lesions need to be treated, it can significantly affect the patient’s quality of life.
Objectives To determine if acitretin is suitable as a chemopreventative agent against
the development of verrucal keratosis and cuSCC, in patients on BRAF inhibitors.
Methods Patients treated with a BRAF inhibitor, vemurafenib or dabrafenib, for
stage IV metastatic melanoma, who had undergone more than five surgical exci-
sions to remove lesions suggestive of cuSCC, were offered the opportunity to
commence acitretin as a chemopreventative agent. Patients were evaluated every
4 weeks. Clinical and histological data were collected.
Results Eight patients, who had a total of 24 cuSCC removed, were included in
the study. After commencement of acitretin, only five cuSCC were excised from
two patients. The most significant reduction was in a patient who had developed
13 cuSCC over 10 months and only two cuSCC 3 months after commencing aci-
tretin. No modifications in the dose of the BRAF inhibitor were made as a result
of cuSCC in any of these patients.
Conclusions Acitretin should be considered as a chemopreventative agent for VK and
cuSCC in patients taking BRAF inhibitors, before considering dosage reductions.
What’s already known about the topic?
•
The BRAF inhibitors vemurafenib and dabrafenib trigger the development of verru-
cal keratosis (VK) and cutaneous squamous cell carcinomas (cuSCC), requiring
multiple surgical interventions and, in some cases, dose reduction.
What does this study add?
•
Acitretin may be a useful agent in the prevention of VK and cuSCC in patients on
BRAF inhibitors.
•
Acitretin may help avoid dose reduction due to the development of VK and cuSCC
in patients on BRAF inhibitors.
•
The patient’s quality of life is improved as the number of surgical procedures
required is reduced.
© 2013 British Association of Dermatologists 1310 British Journal of Dermatology (2013) 169, pp1310–1313