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

Background: Vemurafenib 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. Objectives: We report the results of monochromator phototesting in one patient recorded before and while taking vemurafenib. Analysis of porphyrin levels was also conducted. Results: After 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. Conclusion: These data confirm vemurafenib induced UVA photosensitivity with a probable phototoxic mechanism not mediated via enhanced porphyrin. (C) 2015 Elsevier B.V. All rights reserved.