背景:培美曲塞(Alimta(®))是新一代抗叶酸剂,用于治疗恶性胸膜间皮瘤和非小细胞肺癌(NSCLC)。我们报告了两例培美曲塞引起的新毒性:下肢硬皮病样硬化。
方法:第一例涉及一名66岁男性患者,从一开始就被诊断为肺腺癌转移,在接受6个疗程顺铂-培美曲塞一线治疗后,维持治疗包括培美曲塞。培美曲塞第四个周期后,他出现了左腿红斑性水肿,后来是双边的。临床上,有疼痛的蜂窝织炎与瘀伤相关。病变出现丹毒样感染,也没有发烧.第二例涉及一名70岁的女性,被诊断患有转移性NSCLC。从培美曲塞的第一个疗程开始,作为维持治疗,她的双腿出现红斑性水肿,没有发烧。在第二道菜之后,我们观察到由两条腿上的红斑-紫罗兰色斑块组成的病变的复发,伴有严重的双侧硬结和疼痛性水肿,与重大功能障碍有关。诊断为双侧丹毒,并给予氯唑西林抗生素治疗。在这两种情况下,培美曲塞停药,当地结局非常缓慢,硬皮病的持久性。
结论:这种皮肤不良反应尚未被识别,导致诊断延迟。它通常最初与双侧丹毒混淆,尽管没有发烧。根据一些研究,皮肤毒性的严重程度可能与患者的叶酸状态有关。因此,补充叶酸和维生素B12联合地塞米松可以降低这种副作用的发生率。紫杉烷类没有复发也没有恶化,已知可诱发硬皮病的化疗药物。我们认为,由于其潜在的严重程度,必须认识到这种皮肤毒性。
BACKGROUND: Pemetrexed (Alimta(®)) is a new-generation antifolate used to treat malignant pleural mesothelioma and non-small cell lung cancer (NSCLC). We report two cases of a new toxicity induced by pemetrexed: scleroderma-like induration of the lower extremities.
METHODS: The first case concerned a 66-year-old man diagnosed with pulmonary adenocarcinoma metastatic from the outset and in whom maintenance treatment comprised pemetrexed after first-line therapy comprising six courses of cisplatin-pemetrexed. After the fourth cycle of pemetrexed, he presented an erythematous oedema of the left leg, which was subsequently bilateral. Clinically, there was painful cellulitis associated with areas of bruising. The lesions had an appearance of erysipeloid-like infection, and there was no fever. The second case concerned a 70-year-old woman diagnosed with metastatic NSCLC. From the first course of pemetrexed, given as maintenance therapy, she presented erythematous oedema of both legs, without fever. After the second course, we observed the recurrence of the lesions consisting of erythemato-violaceous plaques on both legs, with severe bilateral indurated and painful oedema, associated with major functional disability. A diagnosis of bilateral erysipelas was made, and antibiotic treatment with cloxacillin was given. In both cases, pemetrexed was discontinued and the local outcome was very slowly favourable, with persistence of scleroderma.
CONCLUSIONS: This cutaneous adverse effect is unrecognized, resulting in delayed diagnosis. It is often initially confused with bilateral erysipelas, despite absence of fever. According to some studies, the severity of the cutaneous toxicity may be connected with patients\' folate status. Thus folate and vitamin B12 supplementation combined with dexamethasone could decrease the incidence of this side effect. There was no recurrence and no worsening with taxanes, chemotherapy agents known to induce scleroderma. We feel that this cutaneous toxicity must be recognised on account of its potential severity.