OPTIMAL USE OF DOCETAXEL (TAXOTERE(R)) - MAXIMIZING ITS POTENTIAL

The safety of docetaxel (Taxotere(R)) has been evaluated in the safety overview population consisting of 1070 patients recruited to phase II trials. These patients received a total of 4989 cycles of therapy (me dian four cycles per patient). Since docetaxel is known to be metaboli zed in the liver, hepatic impairment was predicted to be a risk factor for increased toxicity and was studied prospectively, comparing the 4 2 patients in the overview population with moderate hepatic impairment with the 1028 patients with liver function within normal limits. Hepa tic dysfunction was associated with an increase in the percentage of c ycles of therapy during which febrile neutropenia occurred and the num ber of patients suffering documented infection and severe (grade 3/4) stomatitis. The incidence of toxic death was also increased in patient s with moderate hepatic impairment. The severity of fluid retention, a cumulative toxicity of docetaxel, was found to be reduced, and its on set delayed, by prophylactic treatment with corticosteroids for 5 days , starting 1 day before docetaxel administration. Treatment with corti costeroids was also recommended to reduce the incidence and severity o f hypersensitivity reactions and cutaneous toxicities. The most freque nt severe non-haematological toxicity of docetaxel was asthenia. Other non-haematological toxicities were generally mild or moderate.