经标准膀胱内治疗难治的非肌肉浸润性膀胱癌患者行膀胱内多西紫杉醇治疗的 I 期临床试验的长期临床结局。
Long-term clinical outcomes of a phase I trial of intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to standard intravesical therapy.
机构信息
Department of Urology, Columbia University Medical Center, New York, New York, USA.
出版信息
Urology. 2010 Jan;75(1):134-7. doi: 10.1016/j.urology.2009.06.112. Epub 2009 Nov 13.
OBJECTIVES
To report the long-term clinical outcomes and durability of response after treatment with induction intravesical docetaxel. Most novel agents used to treat bacillus Calmette-Guerin refractory high-grade non-muscle-invasive (NMI) bladder cancer are evaluated only after short follow-up periods. Our previously published phase I trial demonstrated that docetaxel is a safe agent for intravesical therapy with minimal toxicity and no detectable systemic absorption. We sought to determine long-term clinical outcomes after treatment with intravesical docetaxel.
METHODS
Eighteen patients with recurrent Ta (n = 7), T1 (n = 5), and Tis (n = 6) transitional cell carcinoma who experienced treatment failure with at least 1 prior intravesical therapy completed the phase I trial. Docetaxel was administered as 6 weekly intravesical instillations using a dose-escalation model terminated at 0.75 mg/mL. Efficacy was evaluated by interval cystoscopy with biopsies when indicated, cytology, and computed tomography imaging. Follow-up consisted of quarterly cystoscopy, cytology, computed tomography, and biopsy when indicated.
RESULTS
With a median follow-up of 48.3 months, 4 patients (22%) have demonstrated a complete durable response and currently remain disease-free without further treatment. Three patients (17%) had a partial response, defined as a single NMI recurrence with no further therapy for bladder cancer. Eleven patients (61%) failed treatment, and required another intervention. One patient developed stage progression. No delayed toxicities were noted. The median disease-free survival time was 13.3 months.
CONCLUSIONS
After 4 years of follow-up without maintenance therapy, intravesical docetaxel has demonstrated the ability to prevent recurrence in a select number of patients with refractory NMI bladder cancer and warrants further investigation.
目的
报告使用诱导性膀胱内多西紫杉醇治疗后的长期临床结果和反应持久性。大多数用于治疗卡介苗难治性高级非肌肉浸润性（NMI）膀胱癌的新型药物仅在短期随访后进行评估。我们之前发表的 I 期试验表明，多西紫杉醇是一种安全的膀胱内治疗药物，毒性极小，无明显全身吸收。我们试图确定使用膀胱内多西紫杉醇治疗后的长期临床结果。
方法
18 例复发性 Ta（n=7）、T1（n=5）和Tis（n=6）移行细胞癌患者在至少 1 次先前的膀胱内治疗失败后完成了 I 期试验。多西紫杉醇采用剂量递增模型，每周 6 次膀胱内灌注，终止剂量为 0.75mg/ml。疗效通过定期膀胱镜检查和活检、细胞学和计算机断层扫描成像进行评估。随访包括每季度进行膀胱镜检查、细胞学、计算机断层扫描和有指征时的活检。
结果
中位随访 48.3 个月，4 例患者（22%）表现出完全持久的反应，目前无疾病进展，无需进一步治疗。3 例患者（17%）有部分反应，定义为单次 NMI 复发，膀胱癌无进一步治疗。11 例患者（61%）治疗失败，需要进一步干预。1 例患者出现疾病进展。未观察到迟发性毒性。无疾病进展生存时间中位数为 13.3 个月。
结论
在没有维持治疗的情况下随访 4 年后，膀胱内多西紫杉醇已显示出在一定数量的卡介苗难治性 NMI 膀胱癌患者中预防复发的能力，值得进一步研究。
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