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Docetaxel

A Review of its Use for the First-Line Treatment of Advanced Castration-Resistant Prostate Cancer

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An Erratum to this article was published on 01 October 2012

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Abstract

Docetaxel (Taxotere®) is a well established anti-mitotic chemotherapy agent. Among other therapeutic indications, docetaxel plus prednisone is indicated for first-line chemotherapy in patients with castration-resistant prostate cancer (CRPC).

Docetaxel every 3 weeks plus continuous prednisone has been standard first-line chemotherapy in CRPC since demonstrating improved survival compared with the previous standard regimen, mitoxantrone plus prednisone, in the phase III TAX 327 trial in 2004. Since that time, docetaxel has been combined with various agents that demonstrated additive or synergistic activity in preclinical studies in an effort to further improve outcomes, but to date, overall survival has not been extended compared with docetaxel plus prednisone. However, several promising agents are emerging with a potential role in docetaxel-based combinations based on efficacy and manageable toxicity, including bevacizumab, dasatinib and atrasentan.

In the TAX 327 trial, neutropenia was relatively common in the group receiving 3-weekly docetaxel plus prednisone, but infection was rare. The tolerability of a weekly docetaxel regimen also administered in this trial was not significantly different to that of the 3-weekly regimen, except for a lower incidence of grade 3 or 4 neutropenia. However, weekly or 2-weekly docetaxel administration schedules may have a place in very elderly or frail patients in order to improve tolerability compared with the 3-weekly regimen.

In conclusion, docetaxel every 3 weeks plus prednisone remains the optimum first-line chemotherapy for most patients with advanced CRPC until such time that ongoing research with docetaxel and emerging therapeutic agents can demonstrate improved survival.

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    Kate McKeage

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Additional information

Various sections of the manuscript reviewed by: O. Caffo, Medical Oncology Department, Santa Chiara Hospital, Trento, Italy; T. Nelius, Department of Urology, Texas Tech University Health Sciences Center, Lubbock, TX, USA; R. Petrioli, Medical Oncology Unit, University of Siena, Siena, Italy; G.R. Pond, Department of Oncology, McMaster University and Ontario Clinical Oncology Group, Hamilton, ON, Canada.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘docetaxel’ was identified by searching databases (including MEDLINE and EMBASE) for articles published since 1996, bibliographies from published literature, clinical trial registries/databases and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.

Search strategy: MEDLINE and EMBASE search terms were ‘docetaxel’ and ‘castration-resistant metastatic prostate cancer’. Searches were last updated 16 July 2012.

Selection: Studies in patients with castration-resistant metastatic prostate cancer who received docetaxel. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Docetaxel, androgen-independent metastatic prostate cancer, castration-resistant metastatic prostate cancer, hormone-refractory metastatic prostate cancer, pharmacodynamics, pharmacokinetics, therapeutic use.

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McKeage, K. Docetaxel. Drugs 72, 1559–1577 (2012). https://doi.org/10.2165/11209660-000000000-00000

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