| Abstract: |
In oncology, the 1990s has in many respects been the decade of the taxanes, particularly in breast cancer therapy. Preclinical data suggested that scheduling was an important determinant of the antitumor activity of paclitaxel. Initial phase I/II studies established a variety of schedules (based on different doses and infusion durations) for the administration of this drug, with neutropenia or neuropathy being the dose-limiting toxicities. More recently, a regimen in which paclitaxel is infused weekly over 1 hour at doses up to 90 mg/m2 produced little myelosuppression, but substantial antitumor activity. It is hypothesized that this uncoupling of the drug from its expected major toxicity arises due to the shorter period of time in which the plasma paclitaxel concentrations are above a critical level. Along with other approaches, the dose-dense administration of paclitaxel is now subject to randomized, controlled trials. |
