Related Experiment Videos
The clinical pharmacology of paclitaxel (Taxol)
1Johns Hopkins Oncology Center, Division of Pharmacology and Experimental Therapeutics, Baltimore, MD 21287-8934.
Abstract:
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.
Insights
Paclitaxel (TAXOL) is a vital anticancer drug, but limited pharmacologic data hinders optimal use. This review consolidates available clinical pharmacology, pharmacodynamics, and metabolism to guide effective cancer treatment strategies.
Area of Science:
- Oncology
- Pharmacology
- Cancer Therapeutics
Background:
- Paclitaxel (TAXOL) shows efficacy against ovarian, breast, lung, and head/neck cancers.
- Limited preclinical pharmacologic data exists due to paclitaxel's insolubility and assay limitations.
- This hinders the full understanding of biologically significant drug concentrations in preclinical studies.
Purpose of the Study:
- To review the clinical pharmacology of paclitaxel.
- To discuss available pharmacodynamic and metabolic profiles.
- To provide information for designing rational treatment regimens.
Main Methods:
- Review of early single-agent paclitaxel studies (intravenous and intraperitoneal).
- Analysis of paclitaxel in combination chemotherapy regimens.
- Compilation of existing pharmacodynamic and metabolic data.
Main Results:
- Early studies provided initial insights into paclitaxel's clinical pharmacology.
- Pharmacodynamic and metabolic data are being compiled.
- Information is being gathered to optimize dosing and combinations.
Conclusions:
- Consolidating available data is crucial for optimal paclitaxel utilization.
- Understanding pharmacology, pharmacodynamics, and metabolism aids in designing effective cancer therapies.
- This review aims to support rational treatment design for paclitaxel in monotherapy and combination regimens.