1. Adding six cycles of docetaxel to a standard Androgen-deprivation therapy (ADT) therapy resulted in significantly longer overall survival outcomes compared to the standard ADT-alone therapy.
2. The clinical benefit appears to be greater in patients with a higher burden of disease. Further investigations are warranted.
Evidence Rating Level: 1 (Excellent)
Study Rundown: ADT has been the main therapy for metastatic prostate cancer for decades. However, resistance to the therapy is common and survival in these patients is approximately 3 years. Subsequently, docetaxel can be used which compared to other treatments, such as mitoxantrone and prednisone, has shown an approximate 2.5 month longer survival.
This randomized controlled trial specifically investigated whether initiating docetaxel therapy at the beginning of ADT therapy for metastatic hormone-sensitive prostate cancer would result in longer overall survival compared to ADT treatment alone. 790 patients underwent randomization. The combination group demonstrated significantly better cancer control, longer time to castration resistance development, higher rate of decrease in the PSA to less than 0.2 ng/ml levels at 12 months, and overall longer survival compared to the ADT-alone group. In a subgroup analysis of patients with high-volume disease, the combination therapy group had an overall 17.0 month longer overall survival compared to the ADT-alone group.
In-Depth [randomized controlled trial]: The participants were enrolled by ECOG-ACRIN. 790 men aged 36 to 91 were enrolled in either the ADT plus docetaxel group or the ADT-alone group. There were no significant differences between the two groups for baseline patient characteristics. The early docetaxel and ADT group had an overall 13.6 month longer survival compared to the ADT alone group (57.6 months vs. 44.0 months; HR for death in combination group, 0.61; 95% [CI] 0.47 to 0.80; p<0.001). The patients in the combination group demonstrated a significantly lower PSA level to less than 0.2 ng/mL at 12 months compared to the ADT alone group (27.7% vs. 16.8%; p<0.001). The combination group developed resistance significantly later compared to the ADT-alone group (20.2 months vs. 11.7 months; HR 0.61; 95% [CI] 0.51 to 0.72; p<0.001).
The overall survival was more noticeable in the high-volume disease than in the overall study population. This population showed an overall 17.0 month longer survival in the combination group than in the ADT-alone group (49.2 months vs. 32.2 months; HR for death, 0.60; 95% [CI], 0.45 to 0.81; p< 0.001).
Reported adverse events of the combination therapy included: grade 3 or 4 allergic reaction, diarrhea, stomatitis, motor and sensory neuropathy, thromboembolic event, neutropenic fever, and infection with neutropenia.
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