Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery in Patients with High Grade Upper Tract Urothelial Carcinoma.
Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery in Patients with High Grade Upper Tract Urothelial Carcinoma.
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DOI：
10.1097/ju.0000000000000644
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发表时间：
2020-04
期刊：
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通讯作者：
Collaborators
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作者：
Margulis V;Puligandla M;Trabulsi EJ;Plimack ER;Kessler ER;Matin SF;Godoy G;Alva A;Hahn NM;Carducci MA;Hoffman-Censits J;Collaborators
支持新辅助化疗（NAC）治疗高级别（HG）上尿路上皮癌（UTUC）的数据很少。这项多机构前瞻性II期试验研究了HG UTUC NAC后的病理完全缓解（pCR）。计划行肾输尿管切除术（NU）的HG UTUC患者被分配至4个NAC周期，即基线CrCl>50 mL/min的加速甲氨蝶呤、长春碱、阿霉素、顺铂（aMVAC）或30≤CrCl≤50 mL/min的吉西他滨和卡铂（GCa）。主要终点为pCR（ypT 0 N 0）。累积目标是每组30例患者，18%的pCR被认为值得进一步研究，而4%的pCR不值得追求这种方案。每组28例合格患者，成功定义为给定组≥3例pCR（10.7%）。次要终点包括安全性、肾功能和肿瘤学结局。从2015年到2017年，30例患者入组aMVAC组，6例入组GCa组，后者因入组不良而关闭。在29例中位年龄65（40-84）的合格aMVAC患者（23例男性，6例女性）中，80%完成了所有计划的治疗，3例达到ypT 0 N 0（10.3%），第4例达到ypT 0 Nx（pCR= 13.8%，90% CI [4.9 - 28.8]）。1例aMVAC患者因4级脓毒症延迟NU。aMVAC组3-4级毒性发生率为23%，无5级事件。aMVAC NAC在HG UTUC和CrCl>50 mL/min的患者中是安全的，并表现出预定义的活性，pCR为14%。超过60%的患者的最终病理分期≤ ypT 1是令人鼓舞的。总之，这项前瞻性试验的结果支持在符合条件的HG UTUC患者中使用NAC。
Data supporting neoadjuvant chemotherapy (NAC) in high-grade (HG) upper-tract urothelial carcinoma (UTUC) is scant. This multi-institution prospective phase II trial investigated pathologic complete response (pCR) after NAC for HG UTUC. Patients with HG UTUC planned for nephroureterectomy (NU) were assigned to 4 NAC cycles of either accelerated methotrexate, vinblastine, doxorubicin, cisplatin (aMVAC) for baseline CrCl>50 mL/min or gemcitabine and carboplatin (GCa) for 30≤CrCl≤50 mL/min. Primary endpoint was pCR (ypT0N0). Accrual goal was 30 patients per arm. Eighteen percent pCR was considered worthy of further study, while 4% pCR would not justify pursuit of this regimen. With 28 eligible patients per arm, success was defined as ≥3 pCRs (10.7%) in a given arm. Secondary endpoints included safety, renal function, and oncologic outcomes. From 2015–2017, 30 patients enrolled in the aMVAC arm. Six enrolled in the GCa arm, which closed for poor accrual. Of 29 eligible aMVAC patients (23 M, 6F) with median age 65 (40–84), 80% completed all planned treatments, 3 achieved ypT0N0 (10.3%), and a fourth achieved ypT0Nx (pCR=13.8%, 90% CI [4.9 – 28.8]). One aMVAC patient deferred NU due to grade 4 sepsis. Grade 3–4 toxicity rate was 23% in the aMVAC arm, with no grade 5 events. aMVAC NAC in patients with HG UTUC and CrCl>50 mL/min was safe and demonstrated pre-defined activity with 14% pCR. Final pathologic stage ≤ypT1 in over 60% of patients is encouraging. Together, the results of this prospective trial support the use of NAC in eligible patients with HG UTUC.