Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer

Abstract

Background: Androgen-deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone.

Methods: We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area every 3 weeks for six cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone.

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 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 (hazard ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2 ng per milliliter 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, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%.

Conclusions: Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.).

Figure 1. Kaplan–Meier Estimates of Overall Survival

The median duration of follow-up was 28.9 months among all patients (Panel A), 29.2 months among patients with high-volume disease (Panel B), and 27.6 months among patients with low-volume disease (Panel C). ADT denotes androgen-deprivation therapy, and NR not reached.

Figure 2. Hazard Ratios for Death in Subgroups

Eastern Cooperative Oncology Group (ECOG) performance-status scores range from 0 to 5, with higher scores indicating greater disability. Patients were stratified on the basis of an ECOG performance-status score of 0 or 1 versus 2, but because there were so few patients with a score of 2, the analysis was performed on the basis of a score of 0 versus 1 or 2. Race was self-reported; other or unknown race includes black (76 patients), Asian (8), Native American (2), and unknown (30). A high volume of metastases was defined by the presence of visceral metastases or four or more bone lesions with at least one beyond the vertebral bodies and pelvis. Gleason scores range from 2 to 10, with higher scores indicating a more aggressive form of prostate cancer and a worse prognosis. The x axis of the forest plot is scaled according to the natural logarithm of the hazard ratio. The size of the squares is proportional to the inverse of the variance of the log hazard ratio (small squares correspond to large variances).