Docetaxel pharmacology

Engels FK, Sparreboom A, Mathot RA, Verweij J. (2005) Potential for improvement of docetaxel-based chemotherapy A pharmacological review. Br J Cancer 93 173-177. 

Docetaxel acts by disrupting cells microtubular network, which is essential for mitotic and interphase cellular functions. Docetaxel binds to free tubulin and promotes the assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly. Docetaxel is indicated in locally advanced or metastatic breast cancer locally advanced or metastatic non-small-cell lung cancer. The first compound of this series, paclitaxel (Taxol), was isolated from the bark of the Western yew tree in 1971. Paclitaxel and its congenic, the semisynthetic docetaxel (Taxotere), exhibit unique pharmacological actions as... 

The most enthusiastic reports concern the diterpenoids paclitaxel, Taxol (from Taxus brevifolia) and docetaxel, Taxotere (from Taxus baccata) having unique tri- or tetracyclic 20 carbon skeletons extracted from the bark of yew. This tree was known as a toxic plant for animals and humans for centuries. Monroe E. Wall and Mansukh C. Wani, at the Research Triangle Park (Chapel Hill, USA), identified the active principle of the yew tree in 1971. In 1979, Susan Horwitz of the Department of Molecular Pharmacology, Albert Einstein College of Medicine (New York) suggested that paclitaxel s mechanism of action was different from that of any previously known cytotoxic agent. She observed an increase in the mitotic index of P388 cells and an inhibition of human HeLa and mouse fibroblast cells in the G2 and M phases of the cell cycle. 

Pronk LC, Schellens JHM, Planting AST, van den Bent MJ, Hilkens PHE, van der Burg MEL, de Boer-Dennert M, Ma J, Blanc C, Harteveld M, Bruno R, Stoter G, Verweij J, Phase I and pharmacologic study of docetaxel and cisplatin in patients with advanced solid tumors. JClin Oncol 991) 15, 1071-9. 

A-II, were identified. Protein expression profiles determined by MS are thus useful for idenfilying treatment-responsive proteins [25], Toxicity can be severe in case of chemotherapy. MS-based techniques may also be applied to reduce side effects. A study evaluated the association between exposure to unbound docetaxel and neutropenia in cancer patients and identified factors influencing unbound docetaxel clearance. Pharmacokinetic studies and toxicity assessments were performed during the first cycle of therapy. Total docetaxel concentrations were determined by HPLC-MS-MS. The authors conclude that as exposure to unbound docetaxel is closely related to drug-induced hematologic toxicity, this needs to be considered in future pharmacological investigations [26]. 

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