Phase I clinical investigation of fludarabine phosphate by a loading-dose and continuous-infusion schedule.
Phase I clinical investigation of fludarabine phosphate by a loading-dose and continuous-infusion schedule.
复制标题
通过负荷剂量和连续输注方案对磷酸氟达拉滨进行 I 期临床研究。
DOI：
10.1093/jnci/80.6.447
复制
发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Malspeis,L
中科院分区：
文献类型：
--
作者：
Leiby,JM;Grever,MR;Staubus,AE;Neidhart,JA;Malspeis,L
磷酸氟达拉滨在负荷剂量/连续输注方案的I期试验中进行了研究。选择该方案以快速达到并维持体外已显示的浓度，以达到细胞生长的最大抑制。初始剂量为负荷剂量20 mg/m2，随后每24小时连续静脉（CIV）输注30 mg/m2，持续48小时。对于单次剂量递增，负荷剂量保持不变，而CIV剂量增加至45 mg/m2/24小时，持续48小时。剂量限制性毒性为骨髓抑制，尤其是白细胞减少。未发生其他显著毒性。最大耐受剂量为20 mg/m2，静脉推注，随后为48小时CIV输注30 mg/m2/24小时，持续48小时。II期试验的推荐起始剂量为20 mg/m2，静脉推注，随后48小时CIV输注30 mg/m2/24小时。该剂量水平在研究的2例患者中达到了目标血浆水平。[J Natl Cancer Inst 1988;80：447-449]
Fludarabine phosphate was studied in a phase I trial of a loading dose/continuous-infusion schedule. The schedule was chosen to rapidly achieve and maintain concentrations that have been shown in vitro to achieve maximal inhibition of cell growth. The initial level was a loading dose of 20 mg/m2followed by a 48-hour continuous iv (CIV) infusion of 30 mg/m2every 24 hours. For the single-dose escalation, the loading dose was held constant while the CIV dose was increased to 45 mg/m2/24 hours for 48 hours. The dose-limiting toxicity was myelosuppression, especially leukopenia. No other significant toxicity was encountered. The maximum tolerated dose was 20 mg/m2by iv push followed by a 48-hour CIV infusion of 30 mg/m2/24 hours for 48 hours. The recommended starting dose for phase II trials is 20 mg/m2by iv push followed by a 48-hour CIV infusion of 30 mg/m2/24 hours. This dose level achieved the target plasma levels in the 2 patients studied. [J Natl Cancer Inst 1988;80:447–449]