| Paclitaxel, a plant product from Taxus brevifolia, is a | | | | morphologic effects on intracellular microtubules, |
| novel anticancer drug. Its mechanism of action is | | | | including microtubules binding that occurs during all cell |
| different from other cytotoxic agents. Paclitaxel | | | | cycle phases and numerous abnormal mitotic asters. |
| enhances microtubule assembly. Paclitaxel is salvage | | | | Two mechanisms of acquired resistance to the |
| therapy for patients with advanced ovarian cancer | | | | taxanes have been characterized. The resistance cell |
| and for patients with metastatic breast cancer who | | | | lines lack normal microtubules in their mitotic spindles |
| failed to response to prior chemotherapy with | | | | and have inherently slow rate of microtubules |
| standard agents. | | | | assembly when grown in the absence of drug and |
| Paclitaxel, the first organic compound with a taxane | | | | require the continuous presence of the taxanes in |
| ring that has been demonstrated to possess | | | | order to proceed normally. The mutidrug-resistant |
| antineoplastic activity, was isolated in 1967 from the | | | | (mdr) phenotype is also responsible for acquired |
| bark of the Western yew, Taxus brevifolia. Its | | | | resistance to taxanes. This mdr phenotype involves |
| mechanism of action is unique among antineoplastic | | | | the amplification of membrane p-glycoprotein that |
| agents. Paclitaxel promotes the assembly and | | | | functions as a drug efflux pump. |
| stabilization of microtubules which are intracellular | | | | Paclitaxel was initial approved in United States by the |
| structures vital to mitosis and other critical cell | | | | Food and Drug Administration (US FDA) in December |
| functions. In contrast to other clinical useful | | | | 1992 for use in patients with drug-refractory or |
| antimicrotubules agents such as the vinca alkaloids | | | | recurrent epithelial ovarian cancer. In the study |
| and colchicines, which induce net disassembly by | | | | performed at Johns Hopkins, 30% of 40 fully |
| microtubules, paclitaxel shifts the equilibrium towards | | | | evaluable patients had major responses (partial and |
| microtubule assembly. The binding site for paclitaxel | | | | complete responses). Response raking from 1 to 15 |
| on microtubules also appears to be distinct from | | | | months (median, 6 months). Most of the patients, |
| other antimicrotubule agents. It binds preferentially to | | | | including responders, had received extensive prior |
| the beta subunit in the microtubule, rather than | | | | treatments with chemotherapy and radiation. |
| tubulin dimmer. Paclitaxel induces several unique | | | | |