Efficacy and Safety of Combined Androgen Deprivation Therapy (ADT) and Docetaxel Compared with ADT Alone for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and Meta-Analysis: Beyond the Abstract

Androgen-deprivation therapy alone (ADT) continues to be the first line of treatment in most metastatic prostate cancer cases. A combination of docetaxel and prednisone, was the first treatment to significantly improve overall survival in men with metastatic castration-resistant disease. Recent trials tested ADT in combination with docetaxel in the frontline setting with variable results. A recent meta-analysis by Botrel et al. published in the journal PLOS ONE tried to reconcile these results by evaluating the effectiveness and safety of docetaxel associated with standard ADT in patients with metastatic hormone-sensitive metastatic prostate cancer. The authors searched several databases including MEDLINE, EMBASE, LILACS, and CENTRAL for clinical trials testing this combination. The study identified 3 clinical trials (GETUG-AFU 15, CHAARTED, STAMPEDE) including a total of 2,264 patients. 

The analysis demonstrated that patients receiving chemotherapy in combination with ADT had a longer clinical progression-free survival interval (HR = 0.64; 95% CI: 0.55 to 0.75; p<0.00001). There was no significant heterogeneity observed between studies (Chi2 = 0.64; df = 1 [p = 0.42]; I2 = 0%). In addition, the combination of ADT with docetaxel was associated with superior overall survival (OS) compared with ADT alone (HR = 0.73; 95% CI: 0.64 to 0.84; p<0.0001), with moderate heterogeneity (Chi2 = 3.84; df = 2 [p = 0.15]; I2 = 48%).  

Patients with high-volume disease also increased overall survival with combination chemo- hormonal therapy in the combined analysis (HR = 0.67; 95% CI: 0.54 to 0.83; p = 0.0003). As expected patients receiving chemotherapy had higher rates of toxicity including neutropenia, febrile neutropenia and fatigue.

The results of this meta-analysis support the use of Docetaxel in combination with ADT in select patients with hormone sensitive prostate cancer, especially patients with high volume metastatic disease. 

Written by: Bishoy Faltas, MD

References:
Efficacy and Safety of Combined Androgen Deprivation Therapy (ADT) and Docetaxel Compared with ADT Alone for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and Meta-Analysis.Botrel TE, Clark O, Lima Pompeo AC, Horta Bretas FF, Sadi MV, Ferreira U, Borges Dos Reis R. PLoS One. 2016 Jun 16;11(6):e0157660. doi: 10.1371/journal.pone.0157660. eCollection 2016

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