The scientific rationale for developing taxoids.

The taxoid drugs, docetaxel (Taxotere) and paclitaxel (Taxol), represent a new class of antitumour agents which act by promoting the assembly and inhibiting the disassembly of microtubules. Docetaxel has been shown to be more potent than paclitaxel with regard to the formation and stabilization of microtubules in vitro. Docetaxel also has a higher cell uptake than paclitaxel and a longer intracellular retention time. Docetaxel is a more potent antitumour agent than paclitaxel in most model systems. The observation that the cytotoxic concentration for docetaxel is lower than that for paclitaxel in cultures of human haematopoietic cells supports the clinical observation that dose-limiting neutropenia is seen at a lower dose of docetaxel than paclitaxel. The concentration of docetaxel required to kill tumour cells in vitro is well within the plasma concentrations recorded in clinical studies, and docetaxel has shown extensive clinical activity against a variety of solid tumours. Most drugs are used in combination regimens in the clinic and combinations of docetaxel with other agents are under active investigation. The agents to be combined with docetaxel include those which showed synergism with docetaxel in vitro and can be delivered at optimal doses without additive toxicity.