Hayne Dickon, Stockler Martin, McCombie Steve P, Chalasani Venu, Long Anne, Martin Andrew, Sengupta Shomik, Davis Ian D
Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP), Camperdown, NSW, 1450, Australia.
School of Surgery, University of Western Australia, Crawley, WA, 6009, Australia.
BMC Cancer. 2015 May 27;15:432. doi: 10.1186/s12885-015-1431-6.
Despite adequate trans-urethral resection of the bladder tumour (TURBT), non-muscle-invasive bladder cancer (NMIBC) is associated with high rates of recurrence and progression. Instillation of Bacillus Calmette-Guérin (BCG) into the urinary bladder after TURBT (adjuvant intravesical administration) reduces the risk of both recurrence and progression, and this is therefore the standard of care for high-risk tumours. However, over 30 % of people still recur or progress despite optimal delivery of BCG. Our meta-analysis suggests that outcomes might be improved further by using an adjuvant intravesical regimen that includes both mitomycin and BCG. These promising findings require corroboration in a definitive, large scale, randomised phase III trial using standard techniques for intravesical administration.
The BCG + MMC trial (ANZUP 1301) is an open-label, randomised, stratified, two-arm multi-centre phase III trial comparing the efficacy and safety of standard intravesical therapy (BCG alone) against experimental intravesical therapy (BCG and mitomycin) in the treatment of adults with resected, high-risk NMIBC. Participants in the control group receive standard treatment with induction (weekly BCG for six weeks) followed by maintenance (four-weekly BCG for ten months). Participants in the experimental group receive induction (BCG weeks 1, 2, 4, 5, 7, and 8; mitomycin weeks 3, 6, and 9) followed by four-weekly maintenance (mitomycin weeks 13, 17, 25, 29, 37, and 41; BCG weeks 21, 33, and 45). The trial aims to include 500 participants who will be centrally randomised to one of the two treatment groups in a 1:1 ratio stratified by T-stage, presence of CIS, and study site. The primary endpoint is disease-free survival; secondary endpoints are disease activity, time to recurrence, time to progression, safety, health-related quality of life, overall survival, feasibility, and resource use.
This trial is registered with the Australian New Zealand Clinical Trials Registry ( ACTRN12613000513718 ).
尽管经尿道膀胱肿瘤切除术（TURBT）操作得当，但非肌层浸润性膀胱癌（NMIBC）的复发率和进展率仍很高。TURBT术后向膀胱内灌注卡介苗（BCG）（辅助膀胱内给药）可降低复发和进展风险，因此这是高危肿瘤的标准治疗方法。然而，尽管BCG给药方式已达最佳，但仍有超过30%的患者复发或病情进展。我们的荟萃分析表明，使用包含丝裂霉素和BCG的辅助膀胱内治疗方案可能会进一步改善治疗效果。这些有前景的发现需要在一项使用标准膀胱内给药技术的确定性、大规模、随机III期试验中得到证实。
BCG+MMC试验（ANZUP 1301）是一项开放标签、随机、分层、双臂多中心III期试验，比较标准膀胱内治疗（仅使用BCG）与实验性膀胱内治疗（BCG和丝裂霉素）在治疗已切除的高危NMIBC成人患者中的疗效和安全性。对照组参与者接受诱导治疗（每周一次BCG，共六周），随后进行维持治疗（每四周一次BCG，共十个月）。实验组参与者接受诱导治疗（第1、2、4、5、7和8周使用BCG；第3、6和9周使用丝裂霉素），随后每四周进行一次维持治疗（第13、17、25、29、37和41周使用丝裂霉素；第21、33和45周使用BCG）。该试验旨在纳入500名参与者，他们将按1:1的比例被集中随机分配到两个治疗组之一，分层因素为T分期、原位癌的存在情况和研究地点。主要终点是无病生存期；次要终点包括疾病活动度、复发时间、进展时间、安全性、健康相关生活质量、总生存期、可行性和资源利用情况。
该试验已在澳大利亚新西兰临床试验注册中心注册（ACTRN12613000513
