TAXOL (PACLITAXEL), 1ST MOLECULE OF A NEW CLASS OF CYTOTOXIC AGENTS -TAXANES

Taxol is the first of the taxanes, a new class of cytotoxic agents who se cellular target is the microtubules network. Taxol induces the poly merisation of the alpha and beta sub-units of the tubulin. This mechan ism of action which is different from the vinca-alkaloids explains the main cytotoxic activity of paclitaxel through the formation of abnorm al and stable bundles of microtubules. Severe hypersensitivity reactio ns which were seen in early phase I studies are prevented by an oral c orticosteroids and H1 and H2 blockers premedication. Profound neutrope nia is frequent but of short duration explaining that infectious manif estations are rare and neutropenia not cumulative. Thrombopenia and an emia are rare. Neurotoxicity is dose related but severe peripheral neu ropathy is rare. Conduction abnormalities are mainly asymptomatic brad ycardias. In second line ovarian cancer and breast metastatic cancer a noticeable level of activity has been observed, and in lung and head and neck cancer Taxol has proved to be effective.