Lin Chia-Chi, Hsu Chih-Hung, Huang Chao-Yuan, Keng Hsiao-Yi, Tsai Yu-Chieh, Huang Kuo-How, Cheng Ann-Lii, Pu Yeong-Shiau
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, ROC.
Anticancer Drugs. 2007 Apr;18(4):487-91. doi: 10.1097/CAD.0b013e3280126603.
Few treatment options are available for cisplatin-refractory urothelial carcinoma. We evaluated the efficacy and safety of a new regimen composed of gemcitabine and ifosfamide as a second-line salvage chemotherapy for the disease. The gemcitabine and ifosfamide regimen consists of gemcitabine 800 mg/m/day intravenously for 30 min on days 1, 8, and 15; ifosfamide 1500 mg/m/day intravenously for 24 h on days 8-10; and mesna 800 mg intravenously bolus before ifosfamide and 1500 mg/m/day intravenously for 24 h on days 8-11. Cycles are repeated every 28 days. Between 1998 and 2005, 23 patients (median age 66) unresponsive to cisplatin-based chemotherapy (n=10) or who had tumor progression within 6 months of a previous response to cisplatin-based therapy (n=13) were enrolled. The median interval between the two chemotherapy regimens was 1.8 months (range 0.9-5.6). In total, 82 treatment cycles (median 3, range 1-8) were given. The overall response rate was 22% (95% confidence interval 5-39) with one complete response and four partial responses. Twenty-one patients succumbed to the disease. The median progression-free survival and overall survival were 3.5 and 4.8 months, respectively. Grade 3 or 4 leukopenia and thrombocytopenia occurred in 10 and eight patients, respectively. One, two and two patients complicated with grade 3 vomiting, diarrhea and stomatitis were present, respectively. No grade 3 or 4 neurotoxicity or nephrotoxicity was seen in these patients. The gemcitabine and ifosfamide regimen has an acceptable toxicity profile, but shows insufficient clinical activity in patients with cisplatin-refractory urothelial carcinoma to warrant further testing.
对于顺铂难治性尿路上皮癌，可用的治疗选择很少。我们评估了由吉西他滨和异环磷酰胺组成的新方案作为该疾病二线挽救化疗的疗效和安全性。吉西他滨和异环磷酰胺方案包括：吉西他滨800mg/m²/天，于第1、8和15天静脉滴注30分钟；异环磷酰胺1500mg/m²/天，于第8 - 10天静脉滴注24小时；美司钠在异环磷酰胺前静脉推注800mg，并于第8 - 11天以1500mg/m²/天静脉滴注24小时。每28天重复一个周期。1998年至2005年期间，纳入了23例患者（中位年龄66岁），这些患者对基于顺铂的化疗无反应（n = 10）或在先前对基于顺铂的治疗有反应后的6个月内出现肿瘤进展（n = 13）。两种化疗方案之间的中位间隔为1.8个月（范围0.9 - 5.6）。总共进行了82个治疗周期（中位3个，范围1 - 8个）。总缓解率为22%（95%置信区间5 - 39），有1例完全缓解和4例部分缓解。21例患者死于该疾病。中位无进展生存期和总生存期分别为3.5个月和4.8个月。10例和8例患者分别出现3级或4级白细胞减少和血小板减少。分别有1例、2例和2例患者出现3级呕吐、腹泻和口腔炎并发症。这些患者未观察到3级或4级神经毒性或肾毒性。吉西他滨和异环磷酰胺方案具有可接受的毒性特征，但在顺铂难治性尿路上皮癌患者中显示出不足的临床活性，不值得进一步试验。
