A Phase I Trial of Intravesical Cabazitaxel, Gemcitabine and Cisplatin for the Treatment of Nonmuscle Invasive bacillus Calmette-Guérin Unresponsive or Recurrent/Relapsing Urothelial Carcinoma of the Bladder.
A Phase I Trial of Intravesical Cabazitaxel, Gemcitabine and Cisplatin for the Treatment of Nonmuscle Invasive bacillus Calmette-Guérin Unresponsive or Recurrent/Relapsing Urothelial Carcinoma of the Bladder.
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DOI：
10.1097/ju.0000000000000919
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发表时间：
2020-08
期刊：
影响因子：
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通讯作者：
McKiernan JM
中科院分区：
文献类型：
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作者：
DeCastro GJ;Sui W;Pak JS;Lee SM;Holder D;Kates MM;Virk RK;Drake CG;Anderson CB;James B;Abate-Shen CT;McKiernan JM
对于卡介苗无反应或复发/复发性非肌层浸润性膀胱癌患者，多药膀胱内试验有限。在这项研究中，我们研究了膀胱内卡巴他赛，吉西他滨和顺铂在挽救环境中的安全性。这是一项剂量递增、药物递增试验，用于治疗卡介苗无反应或复发/复发性非肌层浸润性膀胱癌患者，这些患者拒绝接受或不适合接受根治性环磷酰胺治疗。所有患者均接受了6周的卡巴他赛、吉西他滨和顺铂序贯给药诱导方案。完全缓解定义为诱导后经尿道膀胱肿瘤切除术无癌症和尿细胞学阴性，而部分缓解允许细胞学阳性。应答者第一年每月继续接受卡巴他赛和吉西他滨维持治疗，第二年每两个月接受一次。共入组18例患者。平均年龄为71岁，中位随访时间为27.8个月（范围为16.3 - 46.9），试验入组前既往膀胱内治疗的平均次数为3.7。9例患者（50%）在卡介苗接种后接受了膀胱内化疗，7例（39%）既往在I期临床试验中接受过治疗。入组时，6例（33%）受试者患有T1疾病，13例（72%）患有原位癌。无剂量限制性毒性。初始部分和完全缓解率分别为94%和89%。1年无复发生存率为0.83（范围0.57 - 0.94），2年估计无复发生存率为0.64（0.32 - 0.84）。在这个高风险和高度预治疗的卡介苗无反应或复发/复发非肌层浸润性膀胱癌病例队列中，卡巴他赛、吉西他滨和顺铂联合膀胱内给药是一种耐受性良好且潜在有效的方案。
For patients with bacillus Calmette-Guérin unresponsive or recurrent/relapsing nonmuscle invasive bladder cancer, multi-agent intravesical trials have been limited. In this study we investigate the safety of intravesical cabazitaxel, gemcitabine and cisplatin in the salvage setting. This was a dose escalation, drug escalation trial for patients with bacillus Calmette-Guérin unresponsive or recurrent/relapsing nonmuscle invasive bladder cancer who declined or were ineligible for radical cystectomy. All patients underwent a 6-week induction regimen of sequentially administered cabazitaxel, gemcitabine and cisplatin. Complete response was defined as no cancer on post-induction transurethral bladder tumor resection and negative urine cytology, while partial response allowed for positive cytology. Responders continued with maintenance cabazitaxel and gemcitabine monthly for the first year and bimonthly for the second year. A total of 18 patients were enrolled. Mean age was 71 years, median followup was 27.8 months (range 16.3 to 46.9) and mean number of previous rounds of intravesical therapies before trial enrollment was 3.7. Nine patients (50%) had received intravesical chemotherapy after bacillus Calmette-Guérin and 7 (39%) were previously treated in a phase I clinical trial setting. At enrollment 6 (33%) subjects had T1 disease and 13 (72%) had carcinoma in situ. There were no dose limiting toxicities. Initial partial and complete response rates were 94% and 89%, respectively. At 1 year recurrence-free survival was 0.83 (range 0.57 to 0.94) and at 2 years estimated recurrence-free survival was 0.64 (0.32 to 0.84). In this high risk and highly pretreated cohort of bacillus Calmette-Guérin unresponsive or recurrent/relapsing nonmuscle invasive bladder cancer cases combination intravesical cabazitaxel, gemcitabine and cisplatin was a well tolerated and potentially effective regimen.