Eriksen Jesper Grau, Kaalund Inger, Clemmensen Ole, Overgaard Jens, Pfeiffer Per
Department of Oncology, Odense University Hospital, 5000, Odense C, Denmark.
Department of Clinical Pathology, Odense University Hospital, Odense, Denmark.
Support Care Cancer. 2017 Jul;25(7):2179-2185. doi: 10.1007/s00520-017-3623-x. Epub 2017 Feb 15.
Cetuximab inhibits the epidermal growth factor receptor (EGFR), and papulopustular eruptions is a frequent side effect. Vitamin K3 (menadione) has preclinically shown to be a potential activator of the EGFR by phosphorylating the receptor (pEGFR). The present randomised study investigated the effect of a vitamin K3 cream on cetuximab-induced rash.
Thirty patients were included in this double-blinded placebo-controlled trial. Patients receiving cetuximab 500 mg/m every second week plus chemotherapy for metastatic cancer were included. In each patient, vitamin K3 cream and placebo were applied twice daily on two separate areas of the skin of minimum 10 × 10 cm for up to 2 months. Papulopustular eruptions were evaluated clinically and monitored by clinical photos. Skin biopsies, from ten patients taken before and after 1 month of treatment from each treatment area, were stained for EGFR and pEGFR.
Application of vitamin K3 cream twice daily during treatment with cetuximab did not reduce the number of papulopustular eruptions, and this was independent of the use of systemic tetracycline. No significant changes in the staining of EGFR or pEGFR were observed in the skin of the vitamin K3-treated area compared to the placebo area.
The present data do not support any clinical or immunohistochemical benefit of using vitamin K3 cream for cetuximab-induced rash.
西妥昔单抗可抑制表皮生长因子受体（EGFR），丘疹脓疱性皮疹是其常见的副作用。维生素K3（甲萘醌）在临床前研究中已显示出通过使受体磷酸化（pEGFR）而成为EGFR潜在激活剂的可能性。本随机研究调查了维生素K3乳膏对西妥昔单抗所致皮疹的影响。
30例患者纳入了这项双盲安慰剂对照试验。纳入接受每两周500mg/m西妥昔单抗联合化疗治疗转移性癌症的患者。对每位患者，维生素K3乳膏和安慰剂每天两次分别涂抹于至少10×10cm的两个不同皮肤区域，持续2个月。对丘疹脓疱性皮疹进行临床评估，并通过临床照片进行监测。从每个治疗区域选取10例患者，在治疗1个月前后进行皮肤活检，对EGFR和pEGFR进行染色。
在使用西妥昔单抗治疗期间，每天两次涂抹维生素K3乳膏并未减少丘疹脓疱性皮疹的数量，且这与全身性四环素的使用无关。与安慰剂区域相比，维生素K3治疗区域皮肤中EGFR或pEGFR的染色未观察到显著变化。
目前的数据不支持使用维生素K3乳膏治疗西妥昔单抗所致皮疹具有任何临床或免疫组化益处。
