Factors Affecting Pharmacokinetic Variability of Docetaxel

Abstract

In the early 1960s, the US National Cancer Institute started a program aimed at the discovery of new anticancer drugs by releasing protocols for widespread screening of substances and extracts from various origins for antineoplastic activity. Of the more than 100,000 compounds from 35,000 plant species tested between 1960 and 1981, paclitaxel, a complex diterpene isolated from the Pacific Yew tree (Taxus brevifolia), proved one of the most interesting and active agents. Extensive studies on the synthesis of paclitaxel analogues and the development of structure-activity relationships have been carried out over the last few decades, and led in 1986 to the development of docetaxel, a semisynthetic taxane derivative prepared from a noncytotoxic precursor isolated from the European Yew tree (Taxus baccata). Following an extensive clinical evaluation program that started in 1990, docetaxel has currently been recognized as one of the most widely active agents available, and it has been approved in most countries for the treatment of advanced breast cancer and nonsmall cell lung cancer