Phase I trial of intravesical gemcitabine in bacillus Calmette-Guerin-refractory transitional-cell carcinoma of the bladder

被引:125
作者
Dalbagni, G
Russo, P
Sheinfeld, J
Mazumdar, M
Tong, W
Rabbani, F
Donat, MS
Herr, HW
Sogani, P
dePalma, D
Bojorin, D
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Urol, New York, NY 10021 USA
[2] Mem Sloan Kettering Canc Ctr, Div Epidemiol & Biostat, New York, NY 10021 USA
[3] Mem Sloan Kettering Canc Ctr, Pharmacol & Analyt Lab, New York, NY 10021 USA
[4] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, Div Solid Tumor Oncol, Dept Med, New York, NY 10021 USA
关键词
D O I
10.1200/JCO.2002.02.066
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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收藏
页码:3193 / 3198
页数:6
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