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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

• Six cycles of docetaxel with the onset of hormone therapy in the treatment of the primary metastatic prostate carcinoma with high tumor load (Gillessen et al., 2015). Chemotherapy should be started within the first few months after initiation of hormone therapy.
• Castration-resistant prostate cancer with rapid PSA-doubling time (under 3–6 months) and tumor related pain.

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   mg / m ^{2 docetaxel greater than 60   min i.   v. On day 1, cycle duration 21 days.}

Docetaxel weekly:

30   mg / m ^{2 docetaxel greater than 60   min i.   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.

Brand Names of Docetaxel

Taxotere.

References

  Deutsche Version: Docetaxel