Scheduling of taxanes: a review

Abstract

The taxanes are widely used in the cytotoxic treatment of many solid tumours. Their optimal scheduling, however, remains unconfirmed. Here we review the development of both paclitaxel and docetaxel to identify evidence influencing the choice of schedule. Early work with paclitaxel identified that it exhibits non-linear pharmacokinetics which has important clinical implications. Paclitaxel has been administered with a wide range of infusion times, especially 3-weekly and recently weekly schedules. Clinical activity of a weekly schedule appears at least non-inferior, and, in certain circumstances superior, to the 3-weekly schedule, with improved tolerability. Similarly, docetaxel has been investigated for 3-weekly versus weekly schedule, reporting equivalent efficacy and improved side effect profile for weekly dosing with regards myelosuppression. Both paclitaxel and docetaxel are often used with the monoclonal antibodies trastuzumab and bevacizumab. It would appear that in this setting, activity may be again improved by administering the taxane weekly, especially in combination with trastuzumab. A further recent development is the use of nab-paclitaxel, nanoparticle albumin-bound paclitaxel; this Cremaphor EC-free preparation allows shorter infusion times without premedication. Benefits of a weekly schedule with this newer drug are also emerging from the limited randomised data. Whether the possibly greater efficacy of weekly paclitaxel in particular reflects a biological effect of more frequent exposure of cancer cells to the cytotoxic is less clear as this schedule also allows a higher dose intensity to be delivered. Nevertheless, that after more than 20 years, weekly administration has emerged as the optimal schedule, especially for paclitaxel. In practice, the choice of schedule is a balance between the better tolerability (and possibly efficacy) of weekly treatment balanced against the inconvenience for both the patient and clinic of more frequent visits for chemotherapy.