Kripp Melanie, Prasnikar Nicole, Vehling-Kaiser Ursula, Quidde Julia, Al-Batran Salah-Eddin, Stein Alexander, Neben Kai, Hannig Carla Verena, Tessen Hans Werner, Trarbach Tanja, Hinke Axel, Hofheinz Ralf-Dieter
Medizinische Klinik 3, Hämatologie und Onkologie, Universitätsmedizin Mannheim, Mannheim, Germany.
Hämatologie, Internistische Onkologie und Palliativmedizin, Asklepios Klinik Barmbek, Hamburg, Germany.
Oncotarget. 2017 Sep 23;8(62):105061-105071. doi: 10.18632/oncotarget.21249. eCollection 2017 Dec 1.
Dermatologic toxicities, especially akne-like skin rash, are the most common side-effects associated with anti-epidermal growth factor receptor (EGFR) therapy. Preemptive treatment with oral tetracyclines is recommended as a standard. Topical prophylactic options have thus far not been compared to tetracyclines. In the current study, we sought to establish an alternative topical treatment.
In this multicentre, randomized, open-label phase II study patients with (K)Ras-wildtype colorectal cancer receiving panitumumab were randomized (1:1) to receive either doxycycline 100 mg b.i.d. (standard arm) or erythromycin ointment 2% followed by doxycycline in case of insufficient activity. The primary endpoint was the percentage of patients developing no skin toxicity ≥ grade 2 at any time during the first 8 weeks of panitumumab treatment. Skin toxicity was assessed using the NCI CTCAE v 4.0. Secondary endpoints comprised the assessment of skin toxicity using a more thorough grading system (WoMo score), evaluation of skin-related (DLQI) and global quality of life (EORTC QLQ C30).
In total, 88 patients were included in this trial. 69% of the patients in the erythromycin arm suffered from skin toxicity of grade ≥ 2 versus 63% in the standard arm (.). However, as per WoMo score significantly more patients in the erythromycin arm developed moderate or severe skin toxicity at earlier time points. Skin related and overall quality of life was comparable between both arms.
Based on this data erythromycin cannot be regarded as an alternative to doxycycline as prevention of EGFR-related skin toxicity.
皮肤毒性，尤其是痤疮样皮疹，是与抗表皮生长因子受体（EGFR）治疗相关的最常见副作用。推荐口服四环素进行预防性治疗作为标准方法。迄今为止，局部预防性治疗方案尚未与四环素进行比较。在本研究中，我们试图建立一种替代性的局部治疗方法。
在这项多中心、随机、开放标签的II期研究中，接受帕尼单抗治疗的（K）Ras野生型结直肠癌患者被随机分组（1:1），分别接受每日两次100mg强力霉素治疗（标准组）或2%红霉素软膏治疗，若效果不佳则加用强力霉素。主要终点是在帕尼单抗治疗的前8周内任何时间未发生≥2级皮肤毒性的患者百分比。使用美国国立癌症研究所不良事件通用术语标准第4.0版评估皮肤毒性。次要终点包括使用更全面的分级系统（WoMo评分）评估皮肤毒性、评估皮肤相关生活质量（皮肤病生活质量指数，DLQI）和总体生活质量（欧洲癌症研究与治疗组织核心问卷，EORTC QLQ C30）。
本试验共纳入88例患者。红霉素组69%的患者发生≥2级皮肤毒性，标准组为63%（此处原文括号内容缺失）。然而，根据WoMo评分，红霉素组在更早时间点出现中度或重度皮肤毒性的患者明显更多。两组的皮肤相关生活质量和总体生活质量相当。
基于这些数据，红霉素不能被视为预防EGFR相关皮肤毒性的强力霉素替代药物。
