Drug Interactions of Paclitaxel and Docetaxel and their Relevance for the Design of Combination Therapy

Byline: Lucia Vigano (1), Alberta Locatelli (1), Giacomo Grasselli (1), Luca Gianni (1) Keywords: paclitaxel; docetaxel; combination therapy; pharmacokinetics; pharmacodynamics Abstract: The taxanes' interaction with otheranticancer drugs have been extensivelyinvestigated in in vitro and inanimal models as well as in humans due tothe outstanding antitumor activity in abroad range of malignancies. Paclitaxel anddocetaxel are endowed of a rich and complexpharmacology whereby differentpharmacodynamic effects are observeddepending on the sequence of theiradministration in respect with thecompanion drug, and the type of drug thatis combined. Pharmacokinetic interferenceis often but not always a basis of thepharmacodynamic effect. In addition, thevehicle of clinical formulation, especiallyCremophor EL for paclitaxel, influence thepharmacological effect. Finally, newinteraction based on as yet unknownmechanisms drive the two taxanes tomultiple additive/synergistic relationshipswith new signal transduction drugs, such asmodulators of the epidermal-growth-factorfamily of receptors andfarnesyl-transferase inhibitors. Theongoing effort to better understanding sucha rich pharmacology is worth continuing inview of designing new and bettercombinations of the taxanes. Author Affiliation: (1) Division of Medical Oncology A, Istituto Nazionale dei Tumori di Milano, Milan, Italy Article History: Registration Date: 11/10/2004