Sunscreen Use and Ultraviolet (UV) Radiation Avoidance
The evidence that interventions designed to reduce exposure to UV radiation by the use of sunscreen, protective clothing, or limitation of sun exposure time decrease the incidence of nonmelanoma skin cancer is inadequate. A randomized study suggested a possible reduction in incidence of squamous cell carcinomas (SCCs), but study design and analysis problems complicate interpretation of the results.[1,2]
Updated statistics with estimated new cases and deaths for 2013 (cited American Cancer Society as reference 1).
Cellular and Molecular Classification of Melanoma
Added Carvajal et al. as reference 6.
Stage IV and Recurrent Melanoma
Revised text of the signal transduction inhibitors treatment option to include BRAF inhibitors.
Added text to include a treatment option that states that clinical trials should be considered because of the advances in the development of novel agents and combinations of agents designed to reverse or interrupt aberrant molecular pathways that support tumor growth.
Added text to state that studies to date indicate that both BRAF and MEK (mitogen-activated ERK-[extracellular signal-regulated kinase] activating kinase) inhibitors can significantly impact the natural history of melanoma, although they do not appear to provide a cure as single agents.
Added Dabrafenib as a new subsection.
Added MEK inhibitors as a new subsection.
Added Combinatorial Therapy with Signal Transduction Inhibitors as a new subsection.
Added KIT inhibitors as a new subsection.
Added text to state that an extended schedule and escalated dose of TMZ was compared with DTIC in a multicenter trial randomly assigning 859 patients, but no improvement was seen in overall survival (OS) or progression-free survival for the TMZ group, and this dose and schedule resulted in more toxicity than the standard dose, single-agent DTIC (cited Patel et al. as reference 40 and level of evidence 1iiA).
Added text to state that the design of two recent randomized, phase III trials in previously untreated patients with metastatic melanoma included DTIC as the standard therapy arm; vemurafenib and ipilimumab showed superior OS compared with DTIC in the two separate trials.
Added text to include signal transduction inhibitors, including phosphoinositide-3 kinase and Akt inhibitors as a treatment option.
Added text to the antiangiogenesis agents treatment option to state that preclinical data suggest that increased vascular endothelial growth factor production may be implicated in resistance to BRAF inhibitors (cited Martin et al. as reference 44)..
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