Background
Androgen deprivation, firstly through surgical castration and then through androgen deprivation therapy, has been the mainstay of treatment for metastatic prostate cancer since the 1940s.
The use of antiandrogens with medical or surgical castration has been shown to increase 5-year survival but resistance to ADT occurs in most patients and in these patients docetaxel has been shown to increase survival.
Previous small studies have not shown a benefit of docetaxel given concomitant with ADT but most included only patients with a low tumour burden.
Aim
To assess whether docetaxel therapy at the beginning of ADT would result in longer overall survival (hypothesising that the median overall survival would be 33.3% longer) than ADT alone, in men with metastatic hormone-sensitive prostate cancer.
Methods
Men with metastatic, hormone-sensitive prostate cancer were randomized to receive either ADT plus docetaxel (at a dose of 75 mg/m2 body-surface area every 3 weeks for six cycles) or ADT alone.
No dose modifications of ADT were allowed during the trial and no more than 2 dose modifications of docetaxel. Patients assigned to combination therapy were seen every 3 weeks during docetaxel administration and then every 3 months and those on ADT alone were seen every 3 months.
An intention-to-treat statistical analysis was done.
Results
A total of 790 patients (median age = 63 years) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 months vs. 44.0 months; hazard ratio (HR) for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P<0.001).
The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (HR 0.61; 95% CI, 0.51 to 0.72; P<0.001).
The proportion with a prostate-specific antigen level of less than 0.2 ng/mL at 12 months was 27.7% in the combination group versus 16.8% in the ADT-alone group (P<0.001).
In the combination group, 6.2% had grade 3 or 4 febrile neutropenia, 2.3% grade 3 or 4 infection with neutropenia and 0.5% grade 3 sensory neuropathy and 0.5% grade 3 motor neuropathy.
Conclusion
Six cycles of docetaxel at the beginning of standard ADT for hormone-sensitive metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone.
The benefit appeared to be more pronounced in patients with a higher tumour burden.
