Docetaxel dosage

Docetaxel is an active semisynthetic taxoid, without the schedule-dependent efficacy and somewhat different toxicity issues than those associated with pachtaxel administration. Most of the early docetaxel clinical trials used dosages of 60, 75, or 100 mg/m infused intravenously over 1 hour every 3 weeks. Inihal phase II single-agent docetaxel studies reported response rates from 25% to 38%, median survivals of 9 months, and a 1-year survival rate of about 38% in chemotherapy-naive patients with advanced NSCLC. Docetaxel 75 mg/m every 3 weeks in combination with cisplahn is indicated in previously untreated patients with unresectable NSCLC and also as a second-line single agent (100 mg/m every 3 weeks) against previously platinum-treated NSCLC with response rates of 15% to 21%, median survival of 7 months, and 1-year survival of 25%. °... 

The UK manufacturer of aprepitant recommends caution when it is used with antineoplastics that are metabolised by CYP3A4, particularly irinotecan, because of the possibility of increased toxicity with this drug. They also mention that etoposide, vinoreibine, docetaxel, paclitaxel, ifosfamide, imatinib, vinblastine and vincristine, were given without dosage adjustment for potential interactions, but as this was not a formal interaction study they recommend caution. However, with intravenous docetaxel, it appears that no important changes in pharmacokinetics occur, and therefore dosage adjustments are unlikely to be needed for this drug,... 

In a crossover study 24 patients were given docetaxel 180 mg before and on day 12 of a 15-day course of 200 mL daily of a herbal tea containing cannabis 1 g/L. This was prepared from medicinal-grade cannabis Cannabis sativa L. Flos, variety Bedrocan ) containing the cannabinoids A -tetrahydrocannabinol 18% and cannabidiol 0.8%. The clearance and the AUC of docetaxel were not significantly altered by the cannabis. No dosage adjustments are likely to be needed if docetaxel is given with cannabis. ... 

A recent multi-institution survey in Japan drew attention to an important effect of histamine H2 antagonists on docetaxel-induced skin toxicity. Analyses revealed that administration of H2 blockers was associated with a significantly higher incidence of acral erythema (hand-foot syndrome palmar-plantar erythrodysesthesia compare with hand-foot skin reaction. Sects. 13.3.2 and 13.3.3 and see Fig. 13.1) and facial erythema. Steroids and H2 blockers affect the metabolism of docetaxel by cytochrome P45o3A4 (CYP3A4), but dexamethasone dosage did not change the incidence of hand-foot syndrome or facial edema. 

Pharmacokinetics Docetaxel administered intravenously over 1-2 hours has linear pharmacokinetics and the AUC increases proportionately with dose [117 ]. Plasma protein binding is 76-89% [118 ]. The half-life is 11 hours. Elimination is mainly by biliary excretion into the feces [119 ]. In patients with raised bilirubin and/or liver aminotransferases, there is a 12-27% reduction in docetaxel elimination, and dosage reductions should be considered [117 ]. In patients with raised bilirubin concentrations or aminotransferases more than 3.5 times the upper limit of the reference range, and alkaline phosphatase more than six times, no recommendations for dosage reduction can be made and docetaxel should be avoided [111 ]. 

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