Does adding docetaxel to hormone therapy have any survival benefits in patients with metastatic prostate cancer?

This phase 3 clinical trial assessed the efficacy and safety of chemotherapy drug docetaxel combined with hormone therapy (androgen deprivation therapy or ADT) in patients with metastatic non-castrate prostate cancer.

Androgens (testosterone) are male sex hormones that control the development and maintenance of male characteristics. Androgens play a key role in the growth and development of the prostate gland, also facilitating the growth of prostate cancer. Many prostate cancer treatments lower androgen levels in order to prevent the cancer from growing, a therapy known as androgen deprivation therapy (ADT) or castration therapy. This usually involves medical (drugs that prevent testosterone from binding to specific proteins or receptors on prostate cancer cells) or surgical castration (removal of the testicles, the main testosterone producing organ in men, by surgery). Prostate cancer that has spread to other organs (metastatic), but that still responds to ADT is called non-castrate (hormone-sensitive) metastatic prostate cancer. If the cancer becomes resistant to hormone therapy (castration-resistant prostate cancer), patients can benefit from chemotherapy.

Docetaxel (Taxotere) is a chemotherapy drug that works by stopping cancer cells from multiplying, which eventually leads to the death of the cancer cells. Previous studies have shown that docetaxel improved survival in castration-resistant prostate cancer patients and it has been approved by the U.S. FDA for the treatment of these patients. This study aimed to evaluate whether there are any benefits of adding docetaxel to ADT therapy in patients with metastatic non-castrate prostate cancer.

Out of the 385 patients who were involved in this study, 192 were randomly assigned to receive ADT and 9 cycles of docetaxel, while the remaining 195 patients received ADT alone. After an average follow up period of 4 years, the median overall survival or OS (defined as the length of time patients survived after the treatment) in patients who received both docetaxel and ADT was 58.9 months (ranging between 50.8 and 69.1 months) compared to 54.2 months in patients treated with ADT alone. The time patients remained with stable disease (biochemical progression free survival) was significantly longer in patients treated with both ADT and docetaxel compared to patients receiving ADT alone (22.9 months versus 12.9 months). However, more side effects were reported in the docetaxel and ADT group than in the group receiving ADT alone. 21% of patients treated with docetaxel and ADT stopped treatment due to toxicity. The most severe side effects reported by these patients were a high risk of infections (neutropenia) and liver damage.

In summary, this study showed that the addition of docetaxel to ADT in patients with non-castrate metastatic prostate cancer significantly improved progression free survival. However, in terms of overall survival there were no significant benefits and the combined treatment had severe side effects that significantly affected patients’ quality of life. Therefore, the authors of this study do not recommend this combined treatment as initial (first-line) therapy in these patients.

This study was partly funded by Sanofi-Aventis, the manufacturer of Taxotere.