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Investigational New Drugs

, Volume 19, Issue 2, pp 179–196 | Cite as

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

  • Lucia Vigano
  • Alberta Locatelli
  • Giacomo Grasselli
  • Luca Gianni
Article

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.

paclitaxel docetaxel combination therapy pharmacokinetics pharmacodynamics 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Lucia Vigano
    • 1
  • Alberta Locatelli
    • 1
  • Giacomo Grasselli
    • 1
  • Luca Gianni
    • 1
  1. 1.Division of Medical Oncology AIstituto Nazionale dei Tumori di MilanoMilanItaly

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