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ADT + docetaxel + prednisone

Development stage
Unknown
Lead developer
Sanofi
Modality
Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Intravenous, Oral, Subcutaneous, Intramuscular
01

Overview

The combination of ADT (androgen-deprivation therapy), docetaxel, and prednisone is a treatment regimen used primarily for prostate cancer. This triplet therapy has been studied in clinical trials for its efficacy in treating metastatic castration-sensitive prostate cancer (mCSPC) and metastatic hormone-refractory prostate cancer (mHRPC). ## Mechanism and Clinical Use This combination therapy works through multiple mechanisms. ADT reduces testosterone levels, inhibiting prostate cancer growth that depends on an­rogens. Docetaxel is a taxane chemotherapy agent that disrupts cell division by binding to microtubules. Prednisone, a corticosteroid, helps manage side effects and may have some anti-cancer properties. The regimen has been evaluated in several clinical trials, including the PEACE-1 and STAMPEDE studies, which assessed the survival benefit of combining these agents[2][4]. While docetaxel was administered without prednisone in the CHAARTED trial, it was given with prednisone in the STAMPEDE study[2]. ## Efficacy and Safety Research has shown that adding prednisone to ADT plus docetaxel can improve radio­graphic pro­gression-free survival and overall survival in patients with metastatic castration-sensitive prostate cancer[1]. However, a 2023 retrospective study suggested limited clinical benefit from adding prednisolone (a similar corticosteroid) to docetaxel and ADT in patients with mHSPC[3]. Regarding safety, a pharma­cokinetic cross-over study found no sig­nificant difference in docetaxel concentrations with or without prednisone, and similar toxicity pro­files were observed in both scenarios[2]. The most common adverse events associated with docetaxel plus prednisolone treatment include alopecia, anorexia, fatigue, and hema­to­logical toxicities such as leu­ko­penia and neu­ro­penia[5]. ## Administration The typical dosing regimen includes: - Docetaxel: 70-75 mg/m² intravenously once every 3 weeks - Prednisone: 5 mg twice daily orally - ADT: Various formulations of LHRH agonists or antagonists via sub­cutaneous or intra­muscular injection[4][5] This combination therapy represents an important treatment option for patients with metastatic prostate cancer, particularly those with high-volume disease or those who are newly diagnosed with hor­mone-sens­itive high-risk metastatic prostate cancer.

Other names
Triplet therapy
02

Targets

GnRHR (Gonadotropin-releasing hormone receptor)GR (Glucocorticoid receptor)AR (Adrenergic receptors)

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