Goto Ayano, Ozawa Yuichi, Koda Keigo, Akahori Daisuke, Koyauchi Takashi, Amano Yusuke, Kakutani Takuya, Sato Yoshiko, Hasegawa Hirotsugu, Matsui Takashi, Yokomura Koshi, Suda Takafumi
Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita Ward, Hamamatsu, Shizuoka 433-8558, Japan.
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka 431-3192, Japan.
Respir Investig. 2018 Mar;56(2):179-183. doi: 10.1016/j.resinv.2017.11.009. Epub 2017 Dec 21.
The management of skin toxicity is crucial for efficient afatinib treatment, but the role of tetracycline class antibiotics (TCs) in managing these rashes is relatively unknown.
We reviewed the clinical records of patients who were administered afatinib for the treatment of non-small cell lung cancer harboring epidermal growth factor receptor mutations between October 2014 and November 2016. Twenty-five patients, who received TCs for the management of afatinib-related skin disorders, were enrolled.
Minocycline was administered orally to participants. Afatinib-related toxic effects, such as rash, diarrhea, and paronychia, were observed in 92%, 92%, and 40% of cases, respectively. Although 24% of diarrhea and 4% of paronychia cases were rated grade 3 or higher, no severe cases of rash were observed during afatinib treatment. Of the 18 afatinib dose reductions, 14 (78%), three (17%), and one (6%) resulted from diarrhea, paronychia, and stomatitis, respectively; no patients required a dose reduction because of rash. When minocycline treatment started, 21 patients (84%) had a rash of grade 1 or less, and three patients had a grade 2 rash. A response to afatinib was observed in 18 patients (72%) and the median duration of afatinib administration was 501 days. An adverse event related to minocycline (grade 1 nausea) was observed in one patient.
A large proportion of the study patients started minocycline before grade 2 rash development and the severity of afatinib-related rash was lower than that previously reported. Oral TCs may be beneficial, especially if started early.
皮肤毒性的管理对于阿法替尼的有效治疗至关重要,但四环素类抗生素(TCs)在处理这些皮疹中的作用相对未知。
我们回顾了2014年10月至2016年11月期间接受阿法替尼治疗携带表皮生长因子受体突变的非小细胞肺癌患者的临床记录。纳入了25例接受TCs治疗阿法替尼相关皮肤疾病的患者。
参与者口服米诺环素。分别在92%、92%和40%的病例中观察到阿法替尼相关的毒性作用,如皮疹、腹泻和甲沟炎。虽然24%的腹泻病例和4%的甲沟炎病例评级为3级或更高,但在阿法替尼治疗期间未观察到严重皮疹病例。在18次阿法替尼剂量减少中,分别有14次(78%)、3次(17%)和1次(6%)是由于腹泻、甲沟炎和口腔炎导致的;没有患者因皮疹需要减少剂量。开始米诺环素治疗时,21例患者(84%)有1级或以下的皮疹,3例患者有2级皮疹。18例患者(72%)观察到对阿法替尼有反应,阿法替尼给药的中位持续时间为501天。1例患者观察到与米诺环素相关的不良事件(1级恶心)。
大部分研究患者在2级皮疹出现之前开始使用米诺环素,且阿法替尼相关皮疹的严重程度低于先前报道。口服TCs可能有益,尤其是早期开始使用时。