James Nicholas D, Liu Wenyu, Pirrie Sarah, Kaur Baljit, Hendron Carey, Ford Daniel, Zarkar Anjali, Viney Richard, Southgate Elizabeth, Desai Amisha, Hussain Syed A
Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB.
Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Edgbaston, Birmingham.
BJU Int. 2022 Jul 31;131(1):63-72. doi: 10.1111/bju.15864.
To assess feasibility and preliminary efficacy of adding cetuximab to standard chemoradiotherapy for muscle-invasive bladder cancer.
TUXEDO was a prospective, single-arm, open-label, phase I/II trial conducted in six UK hospitals. Cetuximab was administered with an initial loading dose of 400mg/m on day 1 of week -1, and then 7-weekly doses of 250mg/m . Radiotherapy schedule was 64Gy/32F with day 1 mitomycin C (12g/m ) and 5-fluorouracil (500mg/m /day) over days 1-5 and 22-26. Patients with T2-4aN0M0 urothelial cancer and a performance status (PS) of 0-1 were eligible. Prior neoadjuvant therapy was permitted. The phase I primary outcome was impact on radiotherapy treatment completion and toxicity experienced during treatment. The phase II primary outcome was local control at three-months post-treatment. ISRCTN identifier: 80733590.
Between Sept-2012 and Oct-2016, 33 patients were recruited; 7 in phase I, 26 in phase II. Three patients in phase II were subsequently deemed ineligible and received no trial therapy. Eight patients discontinued cetuximab due to adverse effects. Median age of patients was 70.1 years (range 60.6-75.1), 20 were PS 0, 27 male and 26 had already received neoadjuvant chemotherapy. In phase I, all patients completed planned radiotherapy, with no delays or dose reductions. Of the 30 evaluable patients in phase II, 25 had confirmed local control 3-months post treatment (77%, 95% CI: 58-90). During the trial there were 18 serious adverse events. The study was halted due to slow accrual.
Phase I data demonstrate it is feasible and safe to add cetuximab to chemoradiotherapy. Exploratory analysis of phase II data provides evidence to consider further clinical evaluation of cetuximab in this setting.
评估在肌肉浸润性膀胱癌的标准放化疗中加入西妥昔单抗的可行性和初步疗效。
TUXEDO是一项在英国六家医院进行的前瞻性、单臂、开放标签的I/II期试验。西妥昔单抗给药方案为：在第-1周第1天给予初始负荷剂量400mg/m²，随后每7周给予剂量250mg/m²。放疗方案为64Gy/32次分割，在第1天给予丝裂霉素C（12mg/m²），并在第1 - 5天和第22 - 26天给予5-氟尿嘧啶（500mg/m²/天）。T2-4aN0M0期尿路上皮癌且体能状态（PS）为0 - 1的患者符合入组条件。允许既往接受过新辅助治疗。I期主要结局是对放疗治疗完成情况和治疗期间所经历毒性的影响。II期主要结局是治疗后三个月时的局部控制情况。国际标准随机对照试验编号：80733590。
2012年9月至2016年10月期间，共招募33例患者；I期7例，II期26例。II期有3例患者随后被判定不符合入组条件，未接受试验治疗。8例患者因不良反应停用西妥昔单抗。患者中位年龄为70.1岁（范围60.6 - 75.1岁），20例PS为0，27例为男性，26例已接受过新辅助化疗。在I期，所有患者均完成了计划的放疗，无延迟或剂量减少情况。在II期的30例可评估患者中，25例在治疗后三个月时确认达到局部控制（77%，95%置信区间：58 - 90）。试验期间发生了18起严重不良事件。该研究因入组缓慢而停止。
I期数据表明在放化疗中加入西妥昔单抗是可行且安全的。对II期数据的探索性分析为在此情况下考虑对西妥昔单抗进行进一步临床评估提供了证据。
