The safety of
docetaxel (
Taxotere) 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 (median four cycles per patient). Since
docetaxel is known to be metabolized in the liver, hepatic impairment was predicted to be a risk factor for increased toxicity and was studied prospectively, comparing the 42 patients in the overview population with moderate hepatic impairment with the 1028 patients with liver function within normal limits. Hepatic dysfunction was associated with an increase in the percentage of cycles of
therapy during which
febrile neutropenia occurred and the number of patients suffering documented
infection and severe (grade 3/4)
stomatitis. The incidence of toxic death was also increased in patients with moderate hepatic impairment. The severity of fluid retention, a cumulative toxicity of
docetaxel, was found to be reduced, and its onset delayed, by prophylactic treatment with
corticosteroids for 5 days, starting 1 day before
docetaxel administration. Treatment with
corticosteroids was also recommended to reduce the incidence and severity of
hypersensitivity reactions and cutaneous toxicities. The most frequent severe non-haematological toxicity of
docetaxel was
asthenia. Other non-haematological toxicities were generally mild or moderate.