Ghiringhelli François, Vincent Julie, Beltjens Françoise, Bengrine Leila, Ladoire Sylvain
INSERM UMR866, Dijon, France.
Faculté de Médecine, Université de Bourgogne, Dijon, France.
Invest New Drugs. 2015 Dec;33(6):1263-6. doi: 10.1007/s10637-015-0295-6. Epub 2015 Oct 22.
Aflibercept is a recombinant fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor (VEGF). This molecule binds to all isoforms of VEGF-A as well as VEGF-B and placental growth factor, preventing them from activating their respective receptors. Aflibercept is used for the treatment of metastatic colorectal cancer (mCRC) in association with irinotecan. For reasons that remain to be elucidated, the addition of aflibercept to irinotecan-based chemotherapy increases the incidence of grade 3-4 diarrhea. We performed systematic colonic biopsies in three patients with grade 3 diarrhea after introduction of fluorouracil, leucovorin, irinotecan and aflibercept treatment for mCRC. For each patient, the diarrhea necessitated treatment discontinuation. Colonoscopy showed normal colonic mucosa. However, histopathological examination of the biopsies performed in these three patients revealed typical features of microscopic colitis. All three patients were treated with budesonide and mesalazine, leading to rapid regression of clinical symptoms. Chemotherapy was reintroduced in all patients, with only mild, grade 1 diarrhea under mesalazine and budesonide treatment. These are the first observations of aflibercept-induced microscopic colitis, and support the use of specific treatment on top of anti-diarrheal treatment in case of important digestive adverse events.
阿柏西普是一种重组融合蛋白，可作为血管内皮生长因子（VEGF）的可溶性诱饵受体。该分子与VEGF-A的所有亚型以及VEGF-B和胎盘生长因子结合，阻止它们激活各自的受体。阿柏西普与伊立替康联合用于治疗转移性结直肠癌（mCRC）。由于尚待阐明的原因，在基于伊立替康的化疗中添加阿柏西普会增加3-4级腹泻的发生率。我们对3例接受氟尿嘧啶、亚叶酸钙、伊立替康和阿柏西普治疗mCRC后出现3级腹泻的患者进行了系统性结肠活检。对于每位患者，腹泻均需要停止治疗。结肠镜检查显示结肠黏膜正常。然而，对这3例患者进行的活检组织病理学检查显示出显微镜下结肠炎的典型特征。所有3例患者均接受布地奈德和美沙拉嗪治疗，临床症状迅速缓解。所有患者均重新开始化疗，在美沙拉嗪和布地奈德治疗下仅出现轻度1级腹泻。这些是关于阿柏西普诱导的显微镜下结肠炎的首次观察结果，并支持在发生严重消化不良反应时，在止泻治疗基础上加用特异性治疗。
