Response of Patients with Taxane-Refractory Advanced Urothelial Cancer to Enfortumab Vedotin, a Microtubule-Disrupting Agent.

Makito Miyake, Nobutaka Nishimura, Tatsuki Miyamoto, Takuto Shimizu, Kenta Ohnishi, Shunta Hori, Yosuke Morizawa, Daisuke Gotoh, Yasushi Nakai, Kazumasa Torimoto, Tomomi Fujii, Kiyohide Fujimoto
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Abstract

Enfortumab vedotin (EV), a nectin-4-directed antibody conjugated to monomethyl auristatin E (MMAE), has been approved for patients with advanced urothelial carcinoma (aUC) previously treated with platinum-based chemotherapy and immune inhibitors. Taxane agents and MMAE share antitumor mechanisms through microtubule disruption, thus raising a notable concern regarding cross-resistance between these drugs. This case report describes two patients with taxane-based chemotherapy-refractory aUC who responded well to EV. A 71-year-old man (case 1) with pT3N0M0 renal pelvic UC showed a partial response to EV in metastatic lesions of the bilateral lungs and right pelvic lymph nodes after three cycles of paclitaxel plus gemcitabine chemotherapy. A 53-year-old man (case 2) with cT3bN2M0 bladder UC underwent platinum-based neoadjuvant chemotherapy and the following radial cystectomy (ypTis ypN0). He developed bilateral lung metastases and showed a complete response to EV in the metastatic lesions after 20 cycles of paclitaxel plus nedaplatin chemotherapy. Our experience of two cases demonstrated that tumor response to EV can be expected in patients with taxane-refractory aUC.

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紫杉烷难治性晚期尿路上皮癌患者对微管干扰剂Enfortumab Vedotin的反应。
Enfortumab vedotin (EV)是一种连接素-4定向抗体偶联单甲基auristatin E (MMAE),已被批准用于先前接受过铂基化疗和免疫抑制剂治疗的晚期尿路上皮癌(aUC)患者。紫杉烷类药物和MMAE通过微管破坏共享抗肿瘤机制,因此引起了对这些药物之间交叉耐药的关注。本病例报告描述了两例紫杉烷类化疗难治性aUC患者,他们对EV反应良好。1例71岁pT3N0M0型肾盆腔UC患者(病例1)在紫杉醇加吉西他滨化疗3个周期后,双侧肺和右侧盆腔淋巴结转移灶对EV有部分反应。一名53岁的cT3bN2M0膀胱UC患者(病例2)接受了基于铂的新辅助化疗和随后的放射状膀胱切除术(ypTis ypN0)。他出现双侧肺转移,在紫杉醇加奈达铂化疗20个周期后,对转移灶的EV完全缓解。我们对两个病例的经验表明,紫杉烷难治性aUC患者对EV的肿瘤反应是可以预期的。
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