The clinical pharmacology of paclitaxel (Taxol).
Although paclitaxel (TAXOL) may be one of the most important antineoplastic agents to emerge from drug screening over the last several decades, with activity demonstrated to date against ovarian, breast, lung, and head and neck cancers, there is a relative lack of pharmacologic data available compared with other agents in similar phases of development. This has been due to the aqueous insolubility of paclitaxel and the inherent insensitivity of standard analytic assays in measuring the full range of biologically significant drug concentrations achieved in small animals, a fact that has limited preclinical pharmacologic studies. This report reviews the clinical pharmacology of paclitaxel as determined during early single-agent studies with the drug administered in various intravenous and intraperitoneal schedules and in combination with other antineoplastic agents. Additionally, available information pertaining to the pharmacodynamic and metabolic profiles of paclitaxel is discussed. Such information may be useful in designing rational treatment regimens using paclitaxel as a single agent and in chemotherapy combinations, potentially resulting in the optimal use of this important agent in cancer chemotherapeutics.
Rowinsky
E K
EK
Johns Hopkins Oncology Center, Division of Pharmacology and Experimental Therapeutics, Baltimore, MD 21287-8934.
Donehower
R C
RC
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002451:Cell Compartmentation; D002986:Clinical Trials as Topic; D004260:DNA Repair; D006801:Humans; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D017239:Paclitaxel