Docetaxel At ADT Initiation Improves Metastatic Prostate Cancer Overall Survival

Giving docetaxel at the start of androgen deprivation therapy prolongs survival in metastatic prostate cancer patients

medwireNews: Men with metastatic hormone-sensitive prostate cancer significantly benefit from docetaxel chemotherapy as they begin androgen deprivation therapy (ADT), suggests research published in The New England Journal of Medicine.

Median overall survival (OS) was 57.6 months for the 397 men randomly assigned to receive docetaxel 75 mg/m2 every 3 weeks for six cycles, compared with 44.0 months for the 393 men given only ADT.

This gave a hazard ratio (HR) for death of 0.61 with the combination treatment, exceeding the study’s target of a 33.3% increase in OS, report Christopher Sweeney, from Dana-Farber Cancer Institute in Boston, Massachusetts, USA, and co-authors.

In all, 513 men had high-volume disease, defined as visceral metastases, or four or more bone lesions with at least one metastatic site outside of the vertebral bodies and pelvis. The 263 of these men treated with ADT plus docetaxel had a median OS of 49.2 months versus 32.2 months for the 250 men given only ADT (HR=0.60).

“The clinical benefit at this early analysis was more pronounced among patients with a high burden of disease”, the researchers therefore conclude. Median OS had not been reached at the time of analysis, after a median of 28.9 months, for men with low-volume disease, they explain.

Docetaxel proved to have a survival benefit in all patient subgroups, irrespective of age, race, performance status, Gleason score, use of combined androgen blockade for at least 30 days, and treatment for skeletal events at time of ADT initiation.

Secondary trial endpoints also supported the use of docetaxel, with a higher proportion of patients given docetaxel plus ADT achieving a prostate-specific antigen level below 0.2 ng/mL at 12 months (27.7 vs 16.8%).

And median time to the development of castration-resistant prostate cancer, defined as biochemical, symptomatic or radiographical disease, was also significantly longer with combined treatment (20.2 vs 11.7 months, HR=0.61), as was time to clinical progression (33.0 vs 19.8 months, HR=0.61).

Adverse effects reported for combined treatment included grade 3 fatigue in 4% of men and grade 3 or 4 allergic reaction in 2%, with around 1% reporting grade 3 diarrhoea, stomatitis, motor neuropathy and sensory neuropathy.

Approximately 6% of patients developed neutropenic fever with 2% experiencing grade 3 or 4 infection with neutropenia. Finally, 1% of patients developed a thromboembolism and one death was recorded as possibly related to docetaxel treatment.


Sweeney CJ, Chen Y-H, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 2015; Advance online publication 5 August. DOI: 10.1056/NEJMoa1503747

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