Paclitaxel is a highly active agent in the treatment of advanced breast cancer. Various options regarding scheduling and combinations are now being tested, opening possibilities to optimize treatment in different settings and with various combinations of drugs. In the present paper, data on the use of single drug paclitaxel in breast cancer shall be reviewed. Paclitaxel pharmacokinetics is non-linear and furthermore, certain toxicities are more dependent on duration of exposure, e.g. granulocytopenia, while other toxicities seem to be more dependent on peak dose, e.g. neurotoxicity. When combining paclitaxel with other drugs, differences in toxicity profile of paclitaxel depending on the schedule should be utilized to tailor optimal combinations. From the data reviewed, it can be concluded that for single drug paclitaxel, the maximal tolerable doses without growth factor support are in the area of 200-250 mg/m2 for 1-hour infusion, 225 mg/m2 for a 3- hour infusion, 175 mg/m2 for 24-hour infusion, and 140 mg/m2 for 96-hour infusion, when paclitaxel is given in 3-week intervals. For weekly administration, most studies find a dose of about 100 mg/m2 per week to be the maximum tolerable. Preclinical and clinical data seem to favor longer infusion times or frequent, e.g. weekly, infusions for single drug paclitaxel, but randomized studies are needed to define optimal dose and scheduling. Given the toxicity and efficacy of weekly scheduling of paclitaxel, this schedule could be a positive new direction in the management of advanced breast cancer.
|Tidsskrift||CME Journal of Gynecologic Oncology|
|Status||Udgivet - 1 dec. 1998|