What is the effect of Docetaxel (generic name) on hormone-refractory metastatic prostate cancer?

From the Guidelines

Docetaxel is a highly effective chemotherapy agent for hormone-refractory metastatic prostate cancer, improving overall survival and quality of life, with the standard regimen being 75 mg/m² administered intravenously every 3 weeks along with daily oral prednisone (5-10 mg) 1. The most recent and highest quality study, published in 2023, supports the use of docetaxel as a category 1 preferred option for treatment of docetaxel-naïve metastatic castration-resistant prostate cancer (mCRPC) 1. Some key points to consider when using docetaxel for hormone-refractory metastatic prostate cancer include:

• Treatment typically continues for 6-10 cycles, depending on response and tolerability 1
• Docetaxel works by binding to microtubules, preventing cell division and ultimately causing cancer cell death
• It has been shown to extend survival by approximately 2-3 months compared to other treatments, with some patients experiencing significant pain relief and reduction in PSA levels 1
• Common side effects include fatigue, nausea, hair loss, peripheral neuropathy, and neutropenia, which may require dose adjustments or supportive care
• Prior to starting treatment, patients should have baseline blood work, and regular monitoring throughout therapy is essential
• For optimal results, docetaxel should be administered by healthcare providers experienced in chemotherapy administration, with appropriate premedication to reduce hypersensitivity reactions Additionally, the 2023 study 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, and that an alternative to every-3-week docetaxel is a biweekly regimen of 50 mg/m2, which may be better tolerated 1. Overall, docetaxel is a valuable treatment option for patients with hormone-refractory metastatic prostate cancer, and its use should be considered in the context of individual patient needs and preferences, with careful monitoring and management of side effects 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 Efficacy results for the Docetaxel Injection every 3 week arm versus the control arm are summarized in Table 18 and Figure 5 Table 18: Efficacy of Docetaxel Injection in the Treatment of Patients with Metastatic Castration- Resistant Prostate Cancer (Intent-to-Treat Analysis) Docetaxel Injection + Prednisone every 3 weeks Mitoxantrone + Prednisone every 3 weeks Number of patients Median survival (months) 95% CI Hazard ratio 95% CI p-value* 335 18.9 (17.0-21.2) 0.761 (0.619-0.936) 0.0094 337 16.5 (14.4-18. 6) -­ -­ -­ *Stratified log-rank test. Threshold for statistical significance = 0.0175 because of 3 arms.

Docetaxel has been shown to have a statistically significant overall survival advantage in patients with metastatic castration-resistant prostate cancer when administered every 3 weeks in combination with prednisone, compared to mitoxantrone. The median survival was 18.9 months for the Docetaxel arm, compared to 16.5 months for the mitoxantrone arm, with a hazard ratio of 0.761 2.

From the Research

Effect of Docetaxel on Hormone-Refractory Metastatic Prostate Cancer

• Docetaxel is a potent inhibitor of microtubular depolymerisation and has been shown to counter the effects of the anti-apoptotic protein Bcl-2 in hormone-refractory metastatic prostate cancer 3.
• Studies have demonstrated that docetaxel can increase overall survival in patients with hormone-refractory metastatic prostate cancer, with median overall survival durations ranging from 17.5 to 18.9 months 3, 4.
• Docetaxel has also been shown to improve prostate-specific antigen response rate, pain, and health-related quality of life in patients with hormone-refractory metastatic prostate cancer 3.
• However, some studies have reported that docetaxel may not improve survival in certain high-risk and poor prognostic groups of patients 5.

Treatment Regimens and Outcomes

• Docetaxel can be administered every 3 weeks, either as a single agent or in combination with prednisone or estramustine 3, 4, 6.
• The efficacy and safety of docetaxel combined with prednisone for the treatment of hormone-refractory prostate cancer are currently being evaluated in a systematic review and meta-analysis 7.
• Re-treatment with docetaxel has been shown to be effective in patients who initially respond to the treatment, with minimal increase in haematological toxicity 4.

Adverse Events

• Common adverse events associated with docetaxel include neutropenia, which can be grade 3 or 4 in severity 3, 5, 4.
• Other adverse events may include fatigue, nausea, and vomiting, although these are often mild to moderate in severity 3.