Phase I trial of intravesical gemcitabine in bacillus Calmette-Guerin-refractory transitional-cell carcinoma of the bladder
Phase I trial of intravesical gemcitabine in bacillus Calmette-Guerin-refractory transitional-cell carcinoma of the bladder
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DOI：
10.1200/jco.2002.02.066
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发表时间：
2002-08-01
影响因子：
45.3
通讯作者：
Bojorin, D
中科院分区：
文献类型：
--
作者：
Dalbagni, G;Russo, P;Bojorin, D
目的：这项I期研究的目的是确定吉西他滨作为膀胱移行细胞癌(TCC)患者膀胱内给药的安全性和毒性。患者和方法：浅表性膀胱癌患者经卡介苗(BCG)膀胱内治疗无效，拒绝膀胱切除术，符合试验条件。吉西他滨膀胱给药1小时，每周2次，每次100毫升氯化钠溶液，共6个疗程。休息1周后，进行为期3周的6个疗程的第二疗程治疗，然后进行疗效评估。结果：18例患者完成治疗：3例为500 mg，6例为11000 mg，3例为1,500 mg，6例为2000 mg。500 mg组未观察到3级或4级毒性。剂量为1,000毫克时，3名患者出现血尿，1名患者出现类似3级手足综合征的皮肤反应。3名患者服用1,500毫克时没有3级或4级毒性。在6名2,000毫克的患者中，1名患者出现了3级血小板减少和中性粒细胞减少，没有感染。7例患者完全反应(细胞学和治疗后活检阴性)，4例混合反应(膀胱活检阴性，细胞学阳性)。结论：吉西他滨在卡介苗耐药的膀胱移行细胞癌中具有较高的活性，值得进一步研究。每周两次的治疗与最小的膀胱刺激和可耐受的骨髓抑制有关。建议每周两次治疗的第11期剂量为2000毫克。(C)2002年，由美国临床肿瘤学会提供。
Purpose: The aim of this phase I study was to determine the safety and toxicity profile of gemcitabine administered as an intravesical agent in patients with transitional-cell carcinoma (TCC) of the bladder.Patients and Methods: Patients with superficial bladder cancer refractory to intravesical bacillus Calmette-Guerin (BCG) therapy and refusing a cystectomy were considered eligible for the trial. Gemcitabine was given in the bladder for 1 hour twice weekly in 100 mL sodium chloride for a total of six treatments. After a 1-week break, a second course of six treatments over 3 weeks was given, followed by response assessment. Four dose levels were explored: 500 mg, 1,000 mg, 1,500 mg, and 2,000 mg.Results: Eighteen patients completed therapy: three at 500 mg, six at 1 1000 mg, three at 1,500 mg, and six at 2,000 mg. No grade 3 or 4 toxicity was observed at 500 mg. At 1,000 mg, three patients developed hematuria and one had a skin reaction resembling grade 3 hand-foot syndrome. Three patients at 1,500 mg had no grade 3 or 4 toxicity. Of six patients at 2,000 mg, one had grade 3 thrombocytopenia and neutropenia without infection. Seven patients had a complete response (negative cytology and posttreatment biopsy), and four patients had a mixed response (negative bladder biopsy but positive cytology).Conclusion: Gemcitabine has substantial activity as an intravesical agent in BCG-refractory TCC and warrants further investigation. Therapy given twice weekly was associated with minimal bladder irritation and tolerable myelosuppression. The recommended phase 11 dose for twice-weekly therapy is 2,000 mg. (C) 2002 by American Society of Clinical Oncology.