The addition of docetaxel at the time of hormone therapy initiation for advanced prostate cancer improved overall survival by 10 months, in a large  randomised controlled trial, published online in the Lancet.

The STAMPEDE study commenced in 2005, and has recruited men with metastatic, high-risk localised or node-positive prostate cancer who were newly diagnosed or had high-risk recurrence following previous local therapy. STAMPEDE utilises a multi-arm approach to test whether addition of other agents at the time of hormone therapy initiation improves overall survival.

In this arm, between October 2005 and March 2013, 2,962 men from centres in the UK and Switzerland, median age 65, were randomly assigned to four groups: standard of care (SOC), SOC plus docetaxel, SOC plus zoledronic acid, and SOC plus both drugs.

Overall, 61% of men had metastatic disease, 15% were node positive, and 24% had high-risk localised disease. Median follow-up was 43 months.

Median survival was 71 months in the SOC group. Addition of zoledronic acid showed no evidence of improved survival. However, patients in the SOC plus docetaxel group had a significant improvement in median survival of 10 months over standard care to 81 months (P = 0.006). Patients who had received SOC plus both drugs had a median survival of 76 months.

Neutropenia and febrile neutropenia were the most common side effects of docetaxel. However, most patients were able to complete all six cycles of treatment.

Initial treatment has changed little over the years for newly diagnosed men with high-risk locally advanced or metastatic prostate cancer.

Since the introduction of GnRH agonists, hormonal therapy has been the mainstay of treatment, with the addition of other agents, including chemotherapy, only when the PSA begins to rise, indicating the onset of hormone resistance.

Docetaxel is an established chemotherapeutic agent, conventionally used for men with hormone-relapsed disease. Used at this later stage in the pathway, docetaxel has shown a median survival benefit of about three months.

The authors conclude: ‘Standard of care should be updated to include docetaxel chemotherapy in suitable patients with metastatic disease, and docetaxel may be considered for men with high-risk non-metastatic prostate cancer with or without radiotherapy.’

There seems little doubt that this change will take place.

Dr Jonathan Rees

James ND, Sydes MR, Clarke NW et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet December 21 2015 published online dx. doi: 10.1016/S0140-6736(15)01037-5. [Epub ahead of print]