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.)

Retracted: Long noncoding RNA MALAT1 enhances the docetaxel resistance of prostate cancer cells via miR‐145‐5p‐mediated regulation of AKAP12

“…Docetaxel (DTX) has been subsequently used as a standard treatment for these patients with castration‐resistant prostate cancer (CRPC) 7. In 2015, 2 trials have been proven to improve survival in men with untreated metastatic prostate cancer through simultaneous addition of DTX and ADT 8, 9. To date, chemotherapy with DTX has been considered as the primary therapeutic choice.…”

Treatment sequence in castration-resistant prostate cancer: A retrospective study in the new anti-androgen era

“…However, it must be considered that the reintroduction of DOC may reduce the possibility that one of the novel treatment options available could then be administered. Furthermore, the situation is complicated by recent clinical trials that may lead to the early administration of DOC in combination with androgen-deprivation therapy, or to novel indications of AA and EZL in pre-DOC patients (13,14). In this setting, certain prior reports have indicated the possibility of the occurrence of cross-resistance when first-line chemotherapy with DOC was administered after the novel hormonal agent AA; by contrast, there have been few instances of DOC rechallenge following failure to respond to AA or other agents (15,16).…”

Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naïve, Metastatic, Castration-Resistant Prostate Cancer

“…[1][2][3][4] These drugs bind b-tubulin and stabilize cellular microtubules, leading to inhibition of microtubule-dependent intracellular trafficking and signaling, mitotic arrest, and apoptotic cell death. [5][6][7] Although taxanes are generally considered antimitotic agents, they also inhibit tumor growth via several different mechanisms.…”