1 21st Century Oncology, Providence, RI.
2 NRG Oncology, Philadelphia, PA.
J Clin Oncol. 2019 Jan 1;37(1):44-51. doi: 10.1200/JCO.18.00537. Epub 2018 Nov 15.
Fluorouracil plus cisplatin and radiation twice a day (FCT) is an established chemoradiation (CRT) regimen for selective bladder-sparing treatment of muscle-invasive bladder cancer. Gemcitabine and once daily radiation (GD) is a well-supported alternative. The current trial evaluates these regimens.
Patients with cT2-4a muscle-invasive bladder cancer were randomly assigned to FCT or GD. Patients underwent transurethral resection and induction CRT to 40 Gy. Patients who achieved a complete response (CR) received consolidation CRT to 64 Gy and others underwent cystectomy. We administered adjuvant gemcitabine/cisplatin chemotherapy. The primary end point was the rate of freedom from distant metastasis at 3 years (DMF3). The trial was not statistically powered to compare regimens, but to assess whether either regimen exceeded a DMF3 benchmark of 75%. Toxicity and efficacy end points, including CR and bladder-intact distant metastasis free survival at 3 years (BI-DMFS3), were assessed.
From December 2008 to April 2014, 70 patients were enrolled, of which 66 were eligible for analysis, 33 per arm. Median follow-up was 5.1 years (range, 0.4 to 7.8 years) for eligible living patients. DMF3 was 78% and 84% for FCT and GD, respectively. BI-DMFS3 was 67% and 72%, respectively. Postinduction CR rates were 88% and 78%, respectively. Of 33 patients in the FCT arm, 21 (64%) experienced treatment-related grade 3 and 4 toxicities during protocol treatment, with 18 (55%), two (6%), and two patients (6%) experiencing grade 3 and 4 hematologic, GI, and genitourinary toxicity, respectively. For the 33 patients in the GD arm, these figures were 18 (55%) overall and 14 (42%), three (9%) and two patients (6%), respectively.
Both regimens demonstrated DMF3 greater than 75%. There were fewer toxicities observed in the GD arm. Either gemcitabine and once daily radiation or a cisplatin-based regimen could serve as a base for future trials of systemic therapy.
氟尿嘧啶联合顺铂和每天两次放疗（FCT）是一种已确立的肌层浸润性膀胱癌选择性保膀胱放化疗方案。吉西他滨联合每日放疗（GD）是一种得到广泛支持的替代方案。本研究评估了这两种方案。
入组 cT2-4a 肌层浸润性膀胱癌患者，随机分配至 FCT 或 GD 组。所有患者均接受经尿道切除术和 40 Gy 的诱导放化疗。获得完全缓解（CR）的患者接受巩固性 64 Gy 放化疗，其余患者行膀胱切除术。术后给予吉西他滨/顺铂辅助化疗。主要研究终点为 3 年时无远处转移率（DMF3）。本研究在统计学上不具备比较两种方案的效能，但可评估这两种方案是否超过 75%的 DMF3 基准。评估的毒性和疗效终点包括 3 年时的无远处转移生存（DMF3）和无膀胱癌远处转移生存（BI-DMFS3）。
2008 年 12 月至 2014 年 4 月，共纳入 70 例患者，其中 66 例符合分析条件，每组 33 例。中位随访时间为 5.1 年（0.4 至 7.8 年）。FCT 和 GD 组的 3 年 DMF3 率分别为 78%和 84%。BI-DMFS3 率分别为 67%和 72%。诱导后 CR 率分别为 88%和 78%。FCT 组 33 例患者中，21 例（64%）在治疗期间出现 3 级和 4 级治疗相关毒性，其中 18 例（55%）、2 例（6%）和 2 例（6%）出现 3 级和 4 级血液学、胃肠道和泌尿生殖系统毒性。GD 组这一数字分别为 18 例（55%）、14 例（42%）、3 例（9%）和 2 例（6%）。
两种方案的 3 年 DMF3 均大于 75%。GD 组的毒性更低。吉西他滨联合每日放疗或顺铂为基础的方案均可作为全身治疗的未来研究基础。
