Its metabolism also occurs

via the CYP3A4 isoenzyme CP-450, and within 7 days of administration, 75% is eliminated in feces (38). Because most docetaxel is broken down in the liver, a reduced dose is recommended for patients with hepatic dysfunction, particularly those with elevated total bilirubin above the upper limit of normal (ULN) or alkaline phosphatase greater than 2.5 times ULN plus ALT and/or AST greater than 1.5 times ULN (38). Renal impairment or age greater than 75 years are an indication for docetaxel dose adjustment (38). Docetaxel is typically administered intravenously at a dose of 60-100 mg/m2 every 21 days (33),(39). The most frequent Inhibitors,research,lifescience,medical dose-limiting toxicities (DLTs) of both paclitaxel and docetaxel include myelosuppression, hypersensitivity reactions, neuropathy, and musculoskeletal effects. Myelosuppression is both dose- and schedule-dependent, Inhibitors,research,lifescience,medical but it is not cumulative, where neutropenia is the principal DLT. The nadir of myelosuppression is usually on the 8th-10th day and complete bone marrow recovery is expected on the 15th-21th day (40). During its early development and in the initial phase II studies, docetaxel was administered at a dose of 100 mg/m2. Inhibitors,research,lifescience,medical In these early studies, neutropenia reached its nadir on the 8th day and resolved on the JAK/stat pathway 15th-21st days of docetaxel infusion, and febrile

neutropenia requiring hospitalization was observed in 10-14% of treated patients (38). Since its early development, docetaxel is now administered at a modified dose of 75 mg/m2. A significant reduction in febrile neutropenia frequency was observed with this dose (38). Taxane

hypersensitivity reactions can be categorized as type 1 (anaphylactoid) Inhibitors,research,lifescience,medical or type 2 (anaphylaxis). Symptoms of an anaphylactoid reaction include dyspnea, flushing, chest pain and tachycardia, where the cause is a surge of histamine release within 2-3 minutes after the administration of the drug. Anaphylaxis is more severe and can even be fatal; Inhibitors,research,lifescience,medical symptoms of anaphylaxis include hypotension, angioedema, and urticaria. Both types of reaction occur during the first two courses, and typically begin during the first 15 minutes of the infusion and resolve 15 minutes prior to the completion of the infusion. Along with antihistamine premedication, the administration of a prophylactic regimen consisting of 3-5 days of steroids beginning 1-2 days prior to treatment can reduce the frequency and the severity of a hypersensitivity reaction (38),(40). Once patients have experienced either type of severe hypersensitivity reaction, the drug is further contraindicated. Fortunately, the incidence of anaphylaxis is low, occurring in only 2% of patients receiving paclitaxel and in 13% of patients receiving docetaxel. Peripheral neuropathy resulting from both axonal degeneration and demyelination (40) is a DLT that is dose-dependent and cumulative.