The addition of docetaxel to androgen-deprivation therapy provides no benefit for patients with non-castrate disease.

Although androgen-deprivation therapy (ADT) remains the standard of care in metastatic prostate cancer, essentially all patients ultimately develop castration resistance and disease progression. Docetaxel (with prednisone) was FDA approved in 2004 for patients with castration-resistant disease after phase III trials demonstrated improvements in both overall survival and disease-related symptoms (e.g., N Engl J Med 2004; 351:1502). However, the optimal timing of docetaxel administration is undefined.

To determine if early use of docetaxel is beneficial in this setting prior to development of castration-resistant disease, European investigators conducted a multicenter, phase III trial involving patients with histologically confirmed adenocarcinoma of the prostate, radiologic evidence of metastatic disease, a Karnofsky score of at least 70%, and adequate organ function; those who had received prior ADT for longer than 2 months before enrollment were excluded. A total of 385 patents were randomized to receive ADT (medical or surgical castration) with or without docetaxel (75 mg/m2 every 3 weeks for 9 cycles; median number of cycles received, 8). Of patients who received ADT alone, 62% subsequently received docetaxel at progression to castration resistance. Of patients who received ADT plus docetaxel, 28% were re-challenged with docetaxel at progression to castration resistance.

At median follow-up of 50 months, biochemical progression-free survival and prostate-specific antigen responses were better in patients receiving ADT plus docetaxel versus ADT alone, but median overall survival (the primary endpoint) was similar between the two groups (58.9 and 54.2 months, respectively). In the ADT plus docetaxel group, febrile neutropenia occurred in 3% of patients and four treatment-related deaths occurred, two of which were neutropenia-related. The authors concluded that docetaxel should not be used in the upfront management of patients with metastatic prostate cancer.

CITATION(S):

Gravis G et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): A randomised, open-label, phase 3 trial. Lancet Oncol 2013 Feb; 14:149.

Sweeney C. Prostate cancer therapy: Going forwards by going backwards. Lancet Oncol 2013 Feb; 14:104.