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The phototoxicity of vemurafenib: An investigation of clinical monochromator phototesting and in vitro phototoxicity testing

Paper ID Volume ID Publish Year Pages File Format Full-Text
30238 44465 2015 6 PDF Available
Title
The phototoxicity of vemurafenib: An investigation of clinical monochromator phototesting and in vitro phototoxicity testing
Abstract

•Erythrocyte porphyrin increases slightly during vemurafenib therapy.•Porphyrin may not be linked to phototoxic mechanism of vemurafenib.•There may be an association between commencing systemic steroid and loss of photosensitivity.

BackgroundVemurafenib is a targeted therapy approved for the treatment of patients with metastatic melanoma harbouring the BRAF V600E mutation. Photosensitivity has been reported in over 50% of patients and has been demonstrated to involve at least the broadband UVA spectrum in most patients. Erythrocyte protoporphyrin levels have also been reported as elevated in some patients.ObjectivesWe report the results of monochromator phototesting in one patient recorded before and while taking vemurafenib. Analysis of porphyrin levels was also conducted.ResultsAfter one month of vemurafenib therapy the patient demonstrated markedly increased light sensitivity in the UVA spectrum between 335 ± 27 nm, 365 ± 27 nm and 400 ± 27 nm. However responses in the UVB (305 ± 5 nm) and blue light (430 ± 27 nm) regions were normal. There was no abnormal immediate erythemal response. Pre-vemurafenib baseline phototesting was normal, as was repeat testing two months later when the patient was taking high doses of systemic steroid. No abnormal porphyrins were detected and the antinuclear antibody test was normal. In parallel studies, HaCaT keratinocytes incubated with vemurafenib were killed by UVA but not by visible (blue) light and did not show evidence of detectable intracellular porphyrin in the presence of the drug.ConclusionThese data confirm vemurafenib induced UVA photosensitivity with a probable phototoxic mechanism not mediated via enhanced porphyrin.

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Keywords
Vemurafenib; Phototoxicity; Monochromator phototesting; Porphyrin
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 151, October 2015, Pages 233–238
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us