Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma.
Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma.
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DOI：
10.1038/sj.bjc.6602673
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发表时间：
2005-07-11
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
本研究旨在确定吉西他滨(2‘-2’-二氟脱氧胞苷)联合循环造血祖细胞支持输注的固定剂量率(FDR)的最大耐受剂量(MTD)，并评价其治疗效果。次要终点是第一疗程测定的吉西他滨和二氟脱氧尿苷(DFdU)的药代动力学，以及循环单核细胞胞苷脱氨酶(CDA)的活性和表达谱。晚期胰腺癌患者在循环造血祖细胞支持下，每2周递增剂量吉西他滨10 mg m−2 min−1。首剂剂量为30 0 0 mg m−2，剂量由5 0 0 mg m−2增加至MTD。总共有23名患者入选。毒副反应轻微或中度，唯一一例用7000 mg m−2治疗的患者因毒性死亡，因此建立了6500 mg m−2的MTD值。总有效率为22.2%。吉西他滨的AUC值呈剂量依赖性增加，而dFdU的AUC值在45 0 0 mg m−2时达到平台期。此外，进展率和生存期与CDA的表达和活性水平显著相关。高剂量吉西他滨的活性并不优于FDR计划强度较低的报告。CDA的表达和活性对预后的预测作用值得进一步研究。
This study aimed to define the maximum-tolerated dose (MTD) of fixed dose rate (FDR) of gemcitabine (2′-2′-difluorodeoxycitidine) infusion with circulating haemopoietic progenitor support and to evaluate the activity of the treatment. Secondary end points were pharmacokinetic of gemcitabine and difluorodeoxyuridina (dFdU) measured at first course and the activity andexpression profile of cytidine deaminase (CdA) on circulating mononuclear cells. Patients with advanced pancreatic carcinoma received escalating dose of gemcitabine 10 mg m−2 min−1 every 2 weeks with circulating haemopoietic progenitor support. First dose level was 3000 mg m−2 and the doses were increased by 500 mg m−2 until MTD. In all, 23 patients were enrolled. Toxicities were mild or moderate; the only patient treated at 7000 mg m−2 died because of toxicity; therefore; the MTD was established at 6500 mg m−2. The overall response rate was 22.2%. The AUC of gemcitabine showed a dose-dependent increase, while the AUC of dFdU reached a plateau at 4500 mg m−2. A significant relationship was found between the AUC of dFdU and CdA expression and activity (P<0.05). Moreover, progression rate and survival were significantly related to CdA expression and activity levels. The activity of high-dose gemcitabine is not superior to that reported with less intensive FDR schedules. The predictive role of CdA expression and activity on outcome deserves further investigation.
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影响因子：
3.4
作者：
POPLIN, EA;CORBETT, T;BAKER, L
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