Woods J A, Ferguson J S, Kalra S, Degabriele A, Gardner J, Logan P, Ferguson J
Photobiology Unit, University of Dundee, Ninewells Hospital & Medical School, Dundee, Scotland, United Kingdom.
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.
J Photochem Photobiol B. 2015 Oct;151:233-8. doi: 10.1016/j.jphotobiol.2015.08.004. Epub 2015 Aug 12.
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.
We report the results of monochromator phototesting in one patient recorded before and while taking vemurafenib. Analysis of porphyrin levels was also conducted.
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.
These data confirm vemurafenib induced UVA photosensitivity with a probable phototoxic mechanism not mediated via enhanced porphyrin.
维莫非尼是一种获批用于治疗携带BRAF V600E突变的转移性黑色素瘤患者的靶向疗法。超过50%的患者报告有光敏反应，并且已证实在大多数患者中至少涉及宽带UVA光谱。也有报道称一些患者的红细胞原卟啉水平升高。
我们报告了一名患者在服用维莫非尼之前和期间进行单色仪光测试的结果。还对卟啉水平进行了分析。
维莫非尼治疗一个月后，患者在335±27nm、365±27nm和400±27nm的UVA光谱中表现出明显增强 的光敏性。然而，UVB（305±5nm）和蓝光（430±27nm）区域的反应正常。没有异常的即时红斑反应。服用维莫非尼之前的基线光测试正常，两个月后患者服用高剂量全身类固醇时的重复测试也正常。未检测到异常卟啉，抗核抗体测试正常。在平行研究中，用维莫非尼孵育的HaCaT角质形成细胞被UVA杀死，但未被可见光（蓝光）杀死，并且在药物存在下未显示可检测到的细胞内卟啉的证据。
这些数据证实维莫非尼可诱导UVA光敏性，其可能的光毒性机制不是通过增强卟啉介导的。
