Phase I trial of intravesical docetaxel in the management of superficial bladder cancer refractory to standard intravesical therapy.
Phase I trial of intravesical docetaxel in the management of superficial bladder cancer refractory to standard intravesical therapy.
复制标题
膀胱内多西紫杉醇治疗标准膀胱内治疗难治性浅表性膀胱癌的 I 期试验。
DOI：
10.3834/uij.1939-4810.2008.09.06
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
M. Benson
中科院分区：
文献类型：
--
作者：
J. McKiernan;P. Masson;A. Murphy;M. Goetzl;C. Olsson;D. Petrylak;M. Desai;M. Benson
目的
使用膀胱内药物治疗浅表性膀胱癌的患者中，高达50%的患者将经历复发。二线膀胱内治疗的有效率从20%到40%不等。对于这些高危患者，新的药物是必要的，以防止复发。多西紫杉醇是一种微管解聚抑制剂，具有独特的物理化学性质，是研究膀胱内药物的理想候选药物。
患者和方法
这项I期试验包括复发的Ta、T1和Tis移行细胞癌患者，这些患者之前至少接受过一次膀胱内治疗，但治疗失败。多西紫杉醇每周滴注6次，起始剂量为5毫克，采用剂量-递增模型，直到达到最大耐受量(MTD)。主要终点是剂量限制毒性(DLT)和MTD。疗效通过膀胱镜活检、细胞学和计算机断层成像进行评估。
结果
18名患者(100%)完成了试验，分期分布包括6名Tis患者，7名Ta患者和5名T1疾病患者。108例输液中无3级或4级DLT发生，无多西紫杉醇全身吸收。18例患者中有8例(44%)出现1级或2级毒性，排尿困难是最常见的。18名患者中有10名(56%)在治疗后的膀胱镜检查和活检中没有发现疾病的证据。经历复发的患者中没有一人病情恶化。
结论
在第一次人类膀胱内临床试验中，多西他赛显示出极低的毒性和无全身吸收。这表明在II期试验中，多西紫杉醇是进一步评估疗效的安全药物。
PURPOSE
Up to 50% of patients treated with intravesical agents for superficial bladder cancer will experience recurrence. Response rates to second-line intravesical therapies range from 20% to 40%. For these high-risk patients, novel agents are necessary to prevent recurrence. Docetaxel is a microtubule depolymerization inhibitor with unique physiochemical properties, making it an excellent candidate for investigation as an intravesical agent.
PATIENTS AND METHODS
This phase I trial included patients with recurrent Ta, T1, and Tis transitional cell carcinoma who experienced treatment failure with at least one prior intravesical treatment. Docetaxel was administered as six weekly instillations at a starting dose of 5 mg, with a dose-escalation model used until a maximum tolerated dose (MTD) was achieved. Primary end points were dose-limiting toxicity (DLT) and MTD. Efficacy was evaluated by cystoscopy with biopsy, cytology, and computed tomography imaging.
RESULTS
Eighteen patients (100%) completed the trial, and the distribution of stages included six patients with Tis, seven with Ta, and five with T1 disease. No grade 3 or 4 DLTs occurred in 108 infusions, and no patient had systemic absorption of docetaxel. Eight (44%) of 18 patients experienced grade 1 or 2 toxicities, with dysuria being the most common. Ten (56%) of 18 patients had no evidence of disease at their post-treatment cystoscopy and biopsy. None of the patients who experienced relapse had disease progression.
CONCLUSION
Intravesical docetaxel exhibited minimal toxicity and no systemic absorption in the first human intravesical clinical trial. This suggests that docetaxel is a safe agent for further evaluation of efficacy in a phase II trial.