Lessons learned from development of docetaxel.
BACKGROUND
Docetaxel has benefited from focused evaluation of its preclinical pharmacology and pharmacokinetics, as well as the evolving areas that are becoming significant to cancer drug development: pharmacogenetics, population pharmacokinetics, and in vivo quantitative pharmacology.


OBJECTIVE
This review juxtaposes the evolution of clinical use of docetaxel and the efforts to limit its observed clinical variability through understanding of its fundamental pharmacology.


METHODS
The clinical review portion of this paper focuses on the examples of breast and lung cancer, to highlight the empiric process that have defined the current drug development process. The exploration of published reports on the clinical pharmacology of docetaxel is then reviewed to emphasize the rich resources available for future development of docetaxel in malignancy.


CONCLUSIONS
As docetaxel moves forward in development, the knowledge gained in the evolution of docetaxel thus far can be leveraged in a model-based drug development schema to effectively use this body of data to make informed decisions about future dose/drug combinations and maximize the chance of further successes in the clinical arena.
Strother
Robert Matthew
RM
Indiana University, Indianapolis, Indiana, USA.
Sweeney
Christopher
C
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D000077143:Docetaxel; D004347:Drug Interactions; D005260:Female; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010597:Pharmacogenetics; D043823:Taxoids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel