Service de Dermatologie, Hôpital Tenon, AP-HP and Faculté de Médecine P&M Curie, Université Paris IV, France.
J Thorac Oncol. 2011 Dec;6(12):2083-9. doi: 10.1097/JTO.0b013e31822e722f.
Pemetrexed is approved to treat non-small cell lung cancer and has an overall favorable toxicity profile. A case of pemetrexed-induced cutaneous adverse events (CAE), i.e., periorbital edema with conjunctivitis and edema of the limbs, leading to severe fluid retention, was diagnosed in our unit. The aim of this study was to evaluate the incidence and risk factors for CAEs.
Patients treated with pemetrexed were identified from a prospective cohort. To detect pemetrexed-associated CAEs, questionnaires were answered by patients and the referring oncologist.
Included were 107 patients treated with four cycles or more of pemetrexed. Pemetrexed-induced CAEs were observed in 37 of 107 (35%) total patients (TPs) and 25 of 47 (53%) alive patients (APs). Conjunctivitis was the most frequent CAE: 27 of 107 (25%) in TPs and 21 of 47 (44%) in APs. Periorbital edema occurred in 16 of 107 (15%) TPs and 14 of 47 (30%) APs. Limb edema was present in 14 of 107 (13%) TPs and 12 of 47 (25%) APs. Only two cases of CAE influenced pemetrexed treatment. No significant differences in age, body surface area, smoking status, and performance status were detected. Patients with CAE had more cycles of pemetrexed (7 versus 5.5; p = 0.028). In univariate and multivariate analyses, gender ratio was statistically different (p = 0.031): 48% (12/25) of women in the CAE group versus only 18% (4/18) in the control group.
Pemetrexed induces frequent conjunctivitis, peripheral edema, and edema of the limbs. Female gender seems to be an independent risk for CAE. CAEs are frequently disabling and symptomatic treatment should be proposed.
培美曲塞已被批准用于治疗非小细胞肺癌，其总体毒性特征良好。我们科室诊断了一例培美曲塞引起的皮肤不良反应（CAE），即眶周水肿伴结膜炎和四肢水肿，导致严重的体液潴留。本研究旨在评估 CAE 的发生率和危险因素。
从前瞻性队列中确定接受培美曲塞治疗的患者。为了检测培美曲塞相关的 CAE，患者和转诊肿瘤学家回答了问卷。
共纳入 107 例接受 4 个周期或以上培美曲塞治疗的患者。107 例患者中，37 例（35%）总患者（TP）和 25 例（53%）存活患者（AP）出现培美曲塞诱导的 CAE。结膜炎是最常见的 CAE：TP 中为 27 例（25%），AP 中为 21 例（44%）。眶周水肿发生于 107 例患者中的 16 例（15%）TP 和 47 例患者中的 14 例（30%）AP。四肢水肿发生于 107 例患者中的 14 例（13%）TP 和 47 例患者中的 12 例（25%）。仅有两例 CAE 影响培美曲塞治疗。未发现年龄、体表面积、吸烟状况和表现状态存在显著差异。发生 CAE 的患者培美曲塞治疗周期更多（7 个周期比 5.5 个周期；p = 0.028）。单因素和多因素分析显示，性别比例存在统计学差异（p = 0.031）：CAE 组中女性占 48%（12/25），而对照组中仅占 18%（4/18）。
培美曲塞可引起频繁的结膜炎、外周水肿和四肢水肿。女性似乎是 CAE 的独立危险因素。CAE 常导致残疾，应提出对症治疗。
