J A Woods1, J S Ferguson2, S Kalra3, A Degabriele3, J Gardner3, P Logan3, J Ferguson3. 1. Photobiology Unit, University of Dundee, Ninewells Hospital & Medical School, Dundee, Scotland, United Kingdom. Electronic address: j.woods@dundee.ac.uk. 2. Photobiology Unit, University of Dundee, Ninewells Hospital & Medical School, Dundee, Scotland, United Kingdom; St George's Hospital, Department of Dermatology, Blackshaw Rd, Tooting, London, United Kingdom. 3. Photobiology Unit, University of Dundee, Ninewells Hospital & Medical School, Dundee, Scotland, United Kingdom.
Abstract
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.
BACKGROUND:Vemurafenib is a targeted therapy approved for the treatment of patients with metastatic melanoma harbouring the BRAFV600E 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.
Authors: Subashini Sharon Gnanendran; Lauren Maree Turner; James Austin Miller; Shelley Ji Eun Hwang; Andrew Charles Miller Journal: Curr Treat Options Oncol Date: 2020-03-19
Authors: Jade Cury-Martins; Adriana Pessoa Mendes Eris; Cristina Martinez Zugaib Abdalla; Giselle de Barros Silva; Veronica Paula Torel de Moura; Jose Antonio Sanches Journal: An Bras Dermatol Date: 2020-02-15 Impact factor: 1.896