What is the role of Docetaxel (docetaxel) in treating high-volume metastatic prostate cancer?

From the Guidelines

Docetaxel should be added to androgen deprivation therapy (ADT) upfront in patients with high-volume metastatic hormone-sensitive prostate cancer, rather than waiting until the cancer becomes castration-resistant, as it has been shown to improve overall survival. For patients with newly diagnosed high-volume metastatic hormone-sensitive prostate cancer, docetaxel is typically administered at 75 mg/m² intravenously every 3 weeks for 6 cycles, alongside ADT 1. This combination therapy has demonstrated a survival benefit of approximately 10-13 months compared to ADT alone, as seen in the CHAARTED and STAMPEDE trials 1. High-volume disease is generally defined as the presence of visceral metastases or four or more bone lesions with at least one beyond the vertebral column and pelvis.

Some key points to consider when using docetaxel in this setting include:

• The importance of patient selection, with those having good performance status being the most suitable candidates for this upfront chemohormonal approach
• The need for regular monitoring of blood counts and liver function due to common side effects such as neutropenia, fatigue, peripheral neuropathy, and fluid retention
• The use of premedication with oral corticosteroids, typically dexamethasone 8 mg twice daily for 3 days starting the day before treatment, to reduce hypersensitivity reactions and fluid retention
• The potential for improved survival outcomes, with a median overall survival of 57.6 months in the combination arm compared to 47.2 months in the ADT arm, as seen in the CHAARTED trial 1

Overall, the addition of docetaxel to ADT upfront in patients with high-volume metastatic hormone-sensitive prostate cancer is now considered standard of care, based on its demonstrated survival advantage and acceptable toxicity profile 1.

From the FDA Drug Label

1.3 Prostate Cancer Docetaxel Injection in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer.

The FDA drug label does not answer the question of whether to wait until cancer becomes castration resistant to add Docetaxel in high-volume metastatic prostate cancer, as it only indicates the use of Docetaxel in combination with prednisone for metastatic castration-resistant prostate cancer 2.

From the Research

Role of Docetaxel in High-Volume Metastatic Prostate Cancer

• The use of Docetaxel in treating high-volume metastatic prostate cancer has been explored in several studies 3, 4, 5, 6, 7.
• The CHAARTED and STAMPEDE trials showed that the addition of Docetaxel to androgen deprivation therapy (ADT) prolonged longevity of men with metastatic hormone-sensitive prostate cancer (mHSPC) 3.
• A study published in the World Journal of Urology found that treatment intensification with upfront Docetaxel or abiraterone plus prednisolone promoted better overall survival compared to ADT alone or combined androgen blockade (CAB) in patients with high-volume mCSPC 4.
• A meta-analysis published in the European Journal of Cancer found that triplet therapy with ADT, Docetaxel, and androgen receptor signalling inhibitors improved overall survival compared to ADT plus Docetaxel in mCSPC patients 5.

Timing of Docetaxel Addition

• The question of whether to wait until cancer becomes castration-resistant to add Docetaxel is complex and depends on various factors, including the patient's overall health and the extent of the disease.
• A study published in European Urology found that the addition of Docetaxel to ADT did not improve survival in patients with metastatic hormone-sensitive prostate cancer, partly due to methodological issues 6.
• However, another study published in Clinical Genitourinary Cancer suggested that combination androgen receptor inhibition and Docetaxel may be the next step in first-line treatment for mCSPC 7.

Key Findings

• The addition of Docetaxel to ADT has been shown to improve overall survival in patients with high-volume mCSPC 4, 5.
• Triplet therapy with ADT, Docetaxel, and androgen receptor signalling inhibitors may provide additional benefits in terms of overall survival 5.
• The timing of Docetaxel addition depends on various factors, including the patient's overall health and the extent of the disease 3, 6.