Taguchi T, Furue H, Niitani H, Ishitani K, Kanamaru R, Hasegawa K, Ariyoshi Y, Noda K, Furuse K, Fukuoka M
Dept. of Surgery, Hospital Attached to the Research Institute for Microbial Diseases of Osaka University.
Gan To Kagaku Ryoho. 1994 Sep;21(12):1997-2005.
A multicenter phase I clinical trial of RP 56976 (docetaxel), a new anticancer drug, was performed with single and repeated doses. Based on the results of phase I clinical trials conducted in the United States and Europe, the starting dose was 10 mg/m2. The dose was subsequently increased to 20, 50, 70 and 90 mg/m2. A dose of 60 mg/m2 was additionally tested. Single administrations of the six dose levels were performed in a total of 27 patients via intravenous drip infusion over one hour. Ten of the patients subsequently received repeated doses at three of the dose levels in the same manner. The dose limiting factor (DLF) of docetaxel is leukopenia (especially, neutropenia). Based on the observation of the DLF, the maximum tolerated dose (MTD) was determined to be 70-90 mg/m2. The white blood cell count reached a nadir about 9.5-19.5 days (median) after administration, and took 7-11 days (median) to recover. Other adverse reactions observed were nausea/vomiting anorexia, alopecia, diarrhea, fatigue and fever, which were all acceptable. The results of this trial suggest that a dosage regimen of 60 mg/m2 at 3- to 4 week intervals is appropriate in an early phase II clinical trial.
对新型抗癌药物RP 56976（多西他赛）进行了一项多中心I期临床试验，采用单次和重复给药。根据在美国和欧洲进行的I期临床试验结果，起始剂量为10mg/m²。随后剂量增加到20、50、70和90mg/m²。另外还测试了60mg/m²的剂量。六个剂量水平的单次给药通过静脉滴注1小时，共对27例患者进行。其中10例患者随后以相同方式在三个剂量水平接受重复给药。多西他赛的剂量限制因素（DLF）是白细胞减少（尤其是中性粒细胞减少）。根据对DLF的观察，确定最大耐受剂量（MTD）为70 - 90mg/m²。给药后白细胞计数在约9.5 - 19.5天（中位数）达到最低点，恢复需要7 - 11天（中位数）。观察到的其他不良反应有恶心/呕吐、厌食、脱发、腹泻、疲劳和发热，均为可接受的。该试验结果表明，在II期临床试验早期，每3至4周间隔给予60mg/m²的给药方案是合适的。
