What is the efficacy of weekly docetaxel (Taxotere) for metastatic castration-resistant prostate cancer?

From the Guidelines

Weekly docetaxel is a viable treatment option for metastatic castration-resistant prostate cancer (mCRPC), offering comparable efficacy to the standard every-3-week dosing with potentially improved tolerability. The recommended weekly regimen is docetaxel 30-35 mg/m² administered intravenously once weekly for 5 out of every 6 weeks, as seen in the TAX327 trial 1. This weekly schedule should be accompanied by daily oral prednisone 5 mg twice daily. Premedication with dexamethasone 8 mg orally 12 hours, 3 hours, and 1 hour before docetaxel infusion is recommended to reduce the risk of hypersensitivity reactions and fluid retention.

Key Considerations

• The weekly regimen offers comparable efficacy to the standard every-3-week dosing (75 mg/m²) but with potentially improved tolerability, particularly regarding myelosuppression, fatigue, and neuropathy, as noted in the TAX327 trial 1 and the NCCN clinical practice guidelines 1.
• This approach may be especially beneficial for elderly patients or those with poor performance status who cannot tolerate the standard regimen.
• Treatment typically continues until disease progression or unacceptable toxicity.
• Regular monitoring of complete blood counts, liver function, and neuropathy symptoms is essential, as emphasized in the NCCN guidelines 1.
• Supportive care including growth factors may be needed based on individual patient risk factors for neutropenic complications.

Evidence-Based Recommendations

• The NCCN panel recommends docetaxel as a category 1 preferred option for treatment of docetaxel-naïve mCRPC 1.
• The panel also suggests that docetaxel can be given as a rechallenge after progression on a novel hormone in the mCRPC setting if given in the castration-sensitive setting, with a category 2A recommendation 1.
• The TAX327 trial demonstrated that 3-weekly docetaxel was superior to the other treatments in its palliative effects and in prolongation of survival, but the weekly regimen may be better tolerated, as seen in the trial 1.

From the FDA Drug Label

The safety and efficacy of Docetaxel Injection in combination with prednisone in patients with metastatic castration-resistant prostate cancer were evaluated in a randomized multicenter active control trial A total of 1006 patients with Karnofsky Performance Status (KPS) ≥60 were randomized to the following treatment groups: Docetaxel Injection 75 mg/m2 every 3 weeks for 10 cycles. Docetaxel Injection 30 mg/m2 administered weekly for the first 5 weeks in a 6-week cycle for 5 cycles. Mitoxantrone 12 mg/m2 every 3 weeks for 10 cycles All 3 regimens were administered in combination with prednisone 5 mg twice daily, continuously. In the Docetaxel Injection every three week arm, a statistically significant overall survival advantage was demonstrated compared to mitoxantrone. In the Docetaxel Injection weekly arm, no overall survival advantage was demonstrated compared to the mitoxantrone control arm

The efficacy of weekly docetaxel for metastatic castration-resistant prostate cancer is not established, as the weekly arm did not demonstrate an overall survival advantage compared to the mitoxantrone control arm 2.

• Key points:
  • No overall survival advantage was demonstrated with weekly docetaxel compared to mitoxantrone.
  • The every 3 week arm showed a statistically significant overall survival advantage compared to mitoxantrone.

From the Research

Efficacy of Weekly Docetaxel for Metastatic Castration-Resistant Prostate Cancer

• The efficacy of weekly docetaxel for metastatic castration-resistant prostate cancer has been studied in several trials 3, 4, 5.
• A study published in 2012 found that treatment with docetaxel in combination with prednisone resulted in an overall PSA response of 73% and a median overall survival of 18.7 months 3.
• Another study published in 2018 found that Abiraterone Acetate, Cabazitaxel, and Enzalutamide presented similar benefits in terms of overall survival compared to control arms, with Enzalutamide showing superiority over progression-free survival and PSA response 4.
• However, the optimal schedule for docetaxel administration (e.g. weekly vs. every 3 weeks) is not clearly established, with one study finding no significant differences between a three-weekly and a three-of-four-weekly schedule 3.

Safety and Tolerability

• Docetaxel has been shown to be generally well-tolerated, with common side effects including myelosuppression, neurotoxicity, and fatigue 3, 5.
• A study published in 2012 found that treatment with docetaxel was well-tolerated, with only two patients withdrawn due to non-haematological toxicity 3.
• Another study published in 2018 found that Abiraterone Acetate presented no significant toxicities compared to control arms 4.

Comparison to Other Treatments

• Docetaxel has been compared to other treatments, including cabazitaxel and abiraterone, in several studies 6, 4.
• A study published in 2017 found that cabazitaxel did not demonstrate superiority over docetaxel in terms of overall survival in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer 6.
• Another study published in 2018 found that Abiraterone Acetate, Cabazitaxel, and Enzalutamide presented similar benefits in terms of overall survival compared to control arms 4.