Gelibter Alain, Malaguti Paola, Di Cosimo Serena, Bria Emilio, Ruggeri Enzo Maria, Carlini Paolo, Carboni Fabio, Ettorre Giuseppe Maria, Pellicciotta Mario, Giannarelli Diana, Terzoli Edmondo, Cognetti Francesco, Milella Michele
Division of Medical Oncology A, Regina Elena National Cancer Institute, Rome, Italy.
Cancer. 2005 Sep 15;104(6):1237-45. doi: 10.1002/cncr.21286.
Gemcitabine infusion at the fixed dose rate of 10 mg/m(2) per minute (FDR-gemcitabine) has pharmacokinetic advantages and may result in improved therapeutic efficacy.
Between April 2002 and September 2003, 40 patients with advanced-stage pancreatic adenocarcinoma (PDAC; n = 27) or biliary tree carcinoma (BTC; n = 13) were treated with weekly FDR-gemcitabine (1000 mg/m(2)). The primary end point was the response rate. The secondary end points were progression-free and overall survival (PFS and OS), tumor marker response, and clinical benefit response (CBR).
The overall response rate (ORR) on an intent-to-treat basis was 15% (95% confidence interval [95% CI], 4-26%). A positive CBR was obtained in 14 of 29 (48%) patients. Seventeen of 25 (68%) patients had a reduction in carbohydrate antigen 19-9 (CA 19-9) of > 25%. The median time to treatment failure and the median PFS were 17 weeks (95% CI, 13-22 weeks) and 19 weeks (95% CI, 15-23 weeks), respectively. The median OS was 40 weeks (95% CI, 36-45 weeks) and the 1-year actuarial survival rate was 25.8%. Multivariate analysis showed that a performance status score of 0-1 at study entry and locally advanced disease were the only independent predictors of longer PFS and OS, whereas a reduction in CA 19-9 serum levels > 75% was an independent predictor of longer PFS, but had no impact on OS. Toxicity was mild with Grade 3-4 neutropenia (according to the National Cancer Institute-Common Toxicity Criteria [version 2.0]) in 18 of 427 treatment weeks (4.2%), and Grade 3 anemia and thrombocytopenia in 6 of 427 treatment weeks (1.4%) and 9 of 427 treatment weeks (2.1%), respectively, and asymptomatic Grade 3-4 transaminase elevation in 21 of 427 treatment weeks (4.9%).
FDR-gemcitabine at the weekly dose of 1000 mg/m(2) demonstrated promising activity, despite negligible toxicity, in patients with advanced-stage PDAC and BTC.
以每分钟10mg/m²的固定剂量率输注吉西他滨（固定剂量率吉西他滨）具有药代动力学优势，可能会提高治疗效果。
在2002年4月至2003年9月期间，40例晚期胰腺腺癌（PDAC；n = 27）或胆管癌（BTC；n = 13）患者接受每周一次的固定剂量率吉西他滨（1000mg/m²）治疗。主要终点是缓解率。次要终点是无进展生存期和总生存期（PFS和OS）、肿瘤标志物反应以及临床获益反应（CBR）。
在意向性治疗基础上的总缓解率（ORR）为15%（95%置信区间[95%CI]，4 - 26%）。29例患者中有14例（48%）获得了阳性CBR。25例患者中有17例（68%）的糖类抗原19 - 9（CA 19 - 9）降低>25%。治疗失败的中位时间和中位PFS分别为17周（95%CI，13 - 22周）和19周（95%CI，15 - 23周）。中位OS为40周（95%CI，36 - 45周），1年精算生存率为25.8%。多因素分析显示，研究入组时体能状态评分为0 - 1以及局部晚期疾病是PFS和OS延长的唯一独立预测因素，而CA 19 - 9血清水平降低>75%是PFS延长的独立预测因素，但对OS无影响。毒性较轻，427个治疗周中有18周（4.2%）出现3 - 4级中性粒细胞减少（根据美国国立癌症研究所通用毒性标准[2.0版]），427个治疗周中有6周（1.4%）出现3级贫血，427个治疗周中有9周（2.1%）出现3级血小板减少，427个治疗周中有21周（4.9%）出现无症状3 - 4级转氨酶升高。
对于晚期PDAC和BTC患者，每周剂量为1000mg/m²的固定剂量率吉西他滨显示出有前景的活性，尽管毒性可忽略不计。
