Intravesical gemcitabine therapy for superficial transitional cell carcinoma of the bladder: A phase I and pharmacokinetic study
Intravesical gemcitabine therapy for superficial transitional cell carcinoma of the bladder: A phase I and pharmacokinetic study
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DOI：
10.1200/jco.2003.09.028
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发表时间：
2003-02-15
影响因子：
45.3
通讯作者：
Egorin, MJ
中科院分区：
文献类型：
--
作者：
Laufer, M;Ramalingam, S;Egorin, MJ
目的：为了确定最大耐受剂量，毒性，每周膀胱内吉西他滨治疗浅表性膀胱cancer.Patients和方法的患者相关的药代动力学：15例复发性浅表性膀胱移行细胞癌谁经历了先前膀胱内治疗失败进行了研究。完全经尿道切除术后2 ~ 4周，膀胱内给予吉西他滨，每周1次，连续6周。停留时间为2小时。研究了吉西他滨及其代谢产物2 '2'-二氟脱氧尿苷（dFdU）在血浆和尿液中的药代动力学。治疗后6周重复膀胱镜检查。结果：三个患者队列依次入组，剂量为500，11000和1,500 mg，溶于100 mL 0.9%NaCl中。2例患者接受2，000 mg/100 mL。另外4例患者接受了2，000 mg溶于50 mL的药物。未观察到4级毒性或临床相关的骨髓抑制。13例可评价患者中有9例在12周时无复发。在接受2，000 mg/50 mL的所有患者的血浆中均短暂存在低浓度吉西他滨（小于或等于1 μ g/mL）。在其他患者的血浆中检测不到吉西他滨。在接受小于1，500 mg的患者的血浆中检测不到dFdU。在剂量大于或等于1，500 mg时，dFdU浓度增加直至90至120分钟，然后几乎没有下降（如果有的话）。血浆dFdU浓度意味着吸收0.5%至5.5%的滴注剂量。排泄的尿液占吉西他滨剂量的61%至100%。无dFdU测定排尿urine.Conclusion：膀胱内吉西他滨，剂量高达2 g/wk，是耐受性良好，与最小的全身吸收，并在治疗浅表性膀胱癌有前途的疗效。(C)2003年，美国临床肿瘤学会。
Purpose : To determine maximum-tolerated dose, toxicities, and pharmacokinetics associated with weekly intravesical gemcitabine therapy in patients with superficial bladder cancer.Patients and Methods: Fifteen patients with recurrent superficial transitional cell bladder carcinoma who experienced prior intravesical therapy failure were studied. Two to 4 weeks after complete transurethral resection, gemcitabine was administered intracesically, once weekly for 6 consecutive weeks. Dwell time was 2 hours. Pharmacokinetics of gemcitabine and its metabolite, 2'2'-difluorodeoxyuridine (dFdU), were studied in plasma and urine. Cystoscopy was repeated 6 weeks after therapy.Results: Three-patient cohorts were enrolled sequentially at doses of 500, 1 1000, and 1,500 mg in 100 mL 0.9% NaCl. Two patients received 2,000 mg in 100 mL. An additional four patients received 2,000 mg in 50 mL. No grade 4 toxicity or clinically relevant myelosuppression was noted. Nine of 13 evaluable patients were recurrence-free at 12 weeks. Low concentrations of gemcitabine (less than or equal to 1 mug/mL) were present transiently in plasma of all patients receiving 2,000 mg in 50 mL. Gemcitabine was undetectable in plasma of other patients. dFdU was undetectable in plasma of patients receiving less than 1,500 mg. At doses greater than or equal to 1,500 mg, dFdU concentrations increased until 90 to 120 minutes and then declined little, if any. Plasma dFdU concentrations implied absorption of 0.5% to 5.5% of instilled dose. Between 61% and 100% of the gemcitabine dose was accounted for in voided urine. No dFdU was measured in voided urine.Conclusion: Intravesical gemcitabine, at doses up to 2 g/wk, is well tolerated, is associated with minimal systemic absorption, and has promising efficacy in treatment of superficial bladder cancer. (C) 2003 by American Society of Clinical Oncology.