Drug interactions of paclitaxel and docetaxel and their relevance for the design of combination therapy

The taxanes' interaction with other anticancer drugs have been extensively investigated in in vitro and in animal models as well as in humans due to t he outstanding antitumor activity in a broad range of malignancies. Paclita xel and docetaxel are endowed of a rich and complex pharmacology whereby di fferent pharmacodynamic effects are observed depending on the sequence of t heir administration in respect with the companion drug, and the type of dru g that is combined. Pharmacokinetic interference is often but not always a basis of the pharmacodynamic effect. In addition, the vehicle of clinical f ormulation, especially Cremophor EL for paclitaxel, influence the pharmacol ogical effect. Finally, new interaction based on as yet unknown mechanisms drive the two taxanes to multiple additive/synergistic relationships with n ew signal transduction drugs, such as modulators of the epidermal-growth-fa ctor family of receptors and farnesyl-transferase inhibitors. The ongoing e ffort to better understanding such a rich pharmacology is worth continuing in view of designing new and better combinations of the taxanes.