The taxanes: dosing and scheduling considerations

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.