TAXANES Paclitaxel It is a complex diterpin taxane obtained from bark of the Western yew tree, which exes cytotoxic action by a novel mechanism. It enhances polymerization of tubulin: a mechanism opposite to that of vinca alkaloids. The microtubules are stabilized and their depolymerization is prevented. This stability results in inhibition of normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic functions. Abnormal arrays or &;bundles&; of microtubules are produced throughout the cell cycle. Cytotoxic action of paclitaxel emphasizes the impoance of tubulin-microtubule dynamic equilibrium. The approved indications of paclitaxel are metastatic ovarian and breast carcinoma after failure of first line chemotherapy and relapse cases. It has also shown efficacy in advanced cases of head and neck cancer, small cell lung cancer, esophageal adenocarcinoma and hormone refractory prostate cancer. The major toxicity is reversible myelosuppression and &;stocking and glove&; neuropathy. Chest pain, ahralgia, myalgia, mucositis and edema can be troublesome.The syndrome of inappropriate ADH secretion is attributed to excessive ADH release. It is defined as less than maximally dilute urine in the presence of plasma hypoosmolality (hyponatremia), without volume depletion or overload, emotional stress, pain, diuretics or other drugs that stimulate ADH secretion. Paclitaxel regimen, cause severe hyponatremia (grade 4) due to documented syndrome of inappropriate antidiuretic hormone secretion (SIADH). ESSENTIALS OF MEDICAL PHARMACOLOGY K.D.TRIPATHI SIXTH EDITION PAGE NO:826