Rose Achim, El-Leithy Tarek, vom Dorp Frank, Zakaria Ahmed, Eisenhardt Andreas, Tschirdewahn Stephan, Rübben Herbert
Department of Urology, HELIOS Marien Klinik, Duisburg, Germany.
Theodor Bilharz Research Institute, Cairo, Egypt.
J Urol. 2015 Oct;194(4):939-43. doi: 10.1016/j.juro.2015.04.073. Epub 2015 Apr 22.
We determined the maximum tolerated dose, safety and effectiveness of intravesical instillation of mistletoe extract after transurethral resection of nonmuscle invasive bladder cancer.
In this single group dose escalation study patients with nonmuscle invasive bladder cancer were treated with weekly instillations of mistletoe extract for 6 weeks. Four weeks before instillation therapy all patients underwent transurethral resection of bladder tumors. During this procedure a marker tumor was left. At 12 weeks after the start of instillation therapy transurethral resection of the marker tumor or biopsy of the former marker tumor location was done so that patients were tumor free when entering followup until week 48. During the followup clinical assessment laboratory tests for safety and cystoscopy were done every 12 weeks.
A total of 36 patients were treated with increasing doses of mistletoe extract. We found no dose limiting toxicity up to a dose of 675 mg of plant extract. Besides local reactions we saw hints that pyrexia may develop. All adverse events were well manageable. At 12 weeks a marker tumor remission rate of 55.6% (95% CI 38.1 to 72.1) was achieved. At 1 year a recurrence rate of 26.3% (95% CI 9.1 to 51.2) was observed.
In this study intravesical instillation of mistletoe extract as treatment in patients with nonmuscle invasive bladder cancer was shown to be safe and well tolerated. Promising data on efficacy were observed and will be further investigated in a phase III study.
我们确定了非肌层浸润性膀胱癌经尿道切除术后膀胱内灌注槲寄生提取物的最大耐受剂量、安全性和有效性。
在这项单组剂量递增研究中，非肌层浸润性膀胱癌患者接受每周一次的槲寄生提取物灌注，共6周。在灌注治疗前4周，所有患者均接受了膀胱肿瘤经尿道切除术。在此过程中留下一个标记肿瘤。在灌注治疗开始12周后，对标记肿瘤进行经尿道切除术或对原标记肿瘤部位进行活检，以便患者在进入48周随访时无肿瘤。在随访期间，每12周进行一次临床评估、安全性实验室检查和膀胱镜检查。
共有36例患者接受了递增剂量的槲寄生提取物治疗。我们发现，在植物提取物剂量高达675 mg时，未发现剂量限制毒性。除局部反应外，我们还发现有发热可能出现的迹象。所有不良事件均易于管理。在12周时，标记肿瘤缓解率达到55.6%（95%可信区间38.1至72.1）。在1年时，观察到复发率为26.3%（95%可信区间9.1至51.2）。
在本研究中，膀胱内灌注槲寄生提取物作为非肌层浸润性膀胱癌患者的治疗方法被证明是安全且耐受性良好的。观察到了关于疗效的有前景的数据，并将在III期研究中进一步研究。
