Rowinsky E K
Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, USA.
Oncology (Williston Park). 1997 Mar;11(3 Suppl 2):7-19.
Optimal dosing and scheduling are among the most important issues being addressed in clinical studies of the taxanes. The results to date indicate that there may not be a single administration schedule that produces optimal antitumor efficacy. Instead, the specific doses of the taxanes relative to each schedule and the overall aggressiveness of the dosing schedule should be considered. There appears to be a threshold taxane dose or concentration below which only negligible antitumor activity is observed, as well as a plateau dose or concentration above which no further antitumor activity occurs. The doses at which both threshold effects and plateauing of dose-response curves occur seem to be inversely proportional to the duration of the administration schedule. For paclitaxel (Taxol), it appears that comparable antitumor effects are achieved with both short (1- and 3-hour) and prolonged (24- and 96-hour) schedules as long as equitoxic dosing regimens are used. The majority of clinical studies with docetaxel have used a somewhat aggressive dosing schedule, 100 mg/m2 over 1 hour, which marks the outer edge of the dosing envelope, but nonrandomized trial results suggest a dose-response relationship in the 60- to 100-mg/m2 dosing range.
最佳给药剂量和给药方案是紫杉烷类药物临床研究中最重要的问题之一。迄今为止的结果表明，可能不存在单一的给药方案能产生最佳抗肿瘤疗效。相反，应考虑相对于每个给药方案的紫杉烷类药物的具体剂量以及给药方案的整体激进程度。似乎存在一个紫杉烷类药物的阈值剂量或浓度，低于该值仅观察到可忽略不计的抗肿瘤活性，同时还存在一个平台剂量或浓度，高于该值不会出现进一步的抗肿瘤活性。出现阈值效应和剂量反应曲线平台化的剂量似乎与给药方案的持续时间成反比。对于紫杉醇（泰素），只要使用等效毒性给药方案，短时间（1小时和3小时）和长时间（24小时和96小时）给药方案似乎都能达到相当的抗肿瘤效果。多西他赛的大多数临床研究使用了一种较为激进的给药方案，即1小时内给予100mg/m²，这处于给药范围的上限，但非随机试验结果表明在60至100mg/m²的给药范围内存在剂量反应关系。
