Dr. med. Dirk Manski

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Docetaxel: Chemotherapy of Prostate Cancer

Mechanism of Action of Docetaxel

Docetaxel inhibits intracellular microtubules depolymerization. The stabilization of the tubular structures by docetaxel leads to a cell cycle stop in the G2M phase and to apoptosis.

Indications for Docetaxel

Pharmacokinetics of Docetaxel

Intravenous administration of docetaxel, cytochrome P450-mediated metabolism, Half-life time 11 h, mainly faecal excretion of docetaxel metabolites.

Side Effects of Docetaxel

Haematological side effects:

Neutropenia grade 3–4 in 32%, the nadir is observed after 7 days and lasts 7 days. Neutropenic fever is rare.

Skin:

Exanthema (maculopapulous) on foot, hand and forearm in 50–70%. Nail toxicity in 35%.

Nervous system:

The occurrence of peripheral sensory neuropathy by docetaxel chemotherapy is frequent and usually reversible. A severe peripheral neuropathy requires a dose reduction of docetaxel and, if there is no improvement, a termination of docetaxel chemotherapy.

Gastrointestinal tract:

The side effects of docetaxel are nausea, vomiting, diarrhea and mucositis.

Further side effects:

Interstitial pneumonia, liver toxicity, lacrimal stenosis. In case of extravasation, severe necrosis must be expected.

Contraindications for Docetaxel:

Patients in poor general condition, previous radionuclide therapy, signs of hepatic failure (bilirubin or liver enzyme elevation over 3.5 times the upper normal limit), creatinine over 2 mg/dl, allergic reaction following docetaxel infusion.

Dose reduction of docetaxel is necessary in case of severe peripheral neuropathy, neutropenia below 1000/μl, thrombopenia below 100000/μl or neutropenic fever (see below). If side effects persist, the treatment should be discontinued. Docetaxel should be paused if neutropenia (below 500/μl) or thrombopenia (below 50000/μl) is present.

Dosage of docetaxel:

Several different regiments of docetaxel are possible. Docetaxel 3-weekly (75 mg/m2) is standard and shows advantages over the weekly dosage (25 mg/m2) in terms of survival (18.9 vs. 17.4 months), pain reduction and tumor responses (12.1 vs 8.2%) (Tannock et al, 2004). The weekly regime offers a higher safety profile. The 2-weekly regimen (50 mg/m2) was better tolerated in a study with the same efficacy as the 3-weekly regimen (Kellokumpu et al, 2013).

 

Premedication before docetaxel infusion

 

Premedication with dexamethasone 8 mg orally, 12 hours, 3 hours and 1 hour before the infusion of docetaxel. Odansetron 8 mg p.o. 2 h before infusion of docetaxel. 5 mg Prednisolone 1-0-1 p.o. for the remaining days of the course.

Docetaxel every 3 weeks:

75 & nbsp; mg / m 2 docetaxel greater than 60 & nbsp; min i. & nbsp; v. On day 1, cycle duration 21 days.

Docetaxel weekly:

30 & nbsp; mg / m 2 docetaxel greater than 60 & nbsp; min i. & nbsp; v. On days 1, 8, 15, 22 and 29. Cycle duration 42 days.

Dose reduction of docetaxel:

After the occurrence of severe skin lesions, severe peripheral neuropathy, neutropenia below 1000 / ll, thrombopenia below 100000 / ll, or in neutropenic fever, the dose of docetaxel should be reduced to 60 mg mg / m sup 2 / Sup> for the next dose. For persistent o.g. Symptoms should stop the docetaxel therapy.

Preparations of Docetaxel:

Brand Names of Docetaxel

Taxotere.





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References



  Deutsche Version: Docetaxel