Efficacy of docetaxel-based chemotherapy following ketoconazole in metastatic castration-resistant prostate cancer: Implications for prior therapy in clinical trials

2013 ◽  
Vol 31 (8) ◽  
pp. 1457-1463 ◽  
Author(s):  
Gregory R. Pond ◽  
Andrew J. Armstrong ◽  
Matthew D. Galsky ◽  
Brian A. Wood ◽  
Lance Leopold ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Castration Resistant Prostate Cancer ◽  
Prior Therapy ◽  
Castration Resistant

scholarly journals Overview of the Development and Use of Akt Inhibitors in Prostate Cancer

2021 ◽  
Vol 11 (1) ◽  
pp. 160
Author(s):  
Anis Gasmi ◽  
Guilhem Roubaud ◽  
Charles Dariane ◽  
Eric Barret ◽  
Jean-Baptiste Beauval ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Phase Ii ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Loss Of Function ◽  
Pten Loss ◽  
Castration Resistant ◽  
Recent Phase ◽  
Phase Ii And Iii

Deregulation of the PI3K-Akt-mTOR pathway plays a critical role in the development and progression of many cancers. In prostate cancer, evidence suggests that it is mainly driven by PTEN loss of function. For many years, the development of selective Akt inhibitors has been challenging. In recent phase II and III clinical trials, Ipatasertib and Capivasertib associated with androgen deprivation therapies showed promising outcomes in patients with metastatic castration-resistant prostate cancer and PTEN-loss. Ongoing trials are currently assessing several Akt inhibitors in prostate cancer with different combinations, at different stages of the disease.

scholarly journals Safety and Efficacy of First-Line Treatments for Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Indirect Comparison

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Haofeng Zheng ◽  
Jialiang Chen ◽  
Wenhan Qiu ◽  
Sijie Lin ◽  
Yanxiong Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Specific Antigen ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Optimal Order ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Safety And Efficacy ◽  
Castration Resistant

Recently, several drugs have been introduced for the first-line treatment of chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), but few studies have compared treatment outcomes directly. This indirect comparison among 10 clinical trials (n= 4870 patients) retrieved from PubMed, Web of Science, Cochrane Collaboration, and ClinicalTrails.gov was performed to assess the safety and efficacy of docetaxel, cabazitaxel, abiraterone, enzalutamide, and sipuleucel-T for the initial treatment of mCRPC. No significant differences in primary outcome (overall survival) were found among initial treatments. However, docetaxel had the highest probability (37.53%) of being the most effective, but at the cost of more adverse events, while enzalutamide was associated with the best secondary outcomes (prostate-specific antigen response, progression-free survival, quality of life, and adverse event profile). Thus, docetaxel is recommended as the first agent used for the chemotherapy of mCRPC, while enzalutamide is recommended as the first nonchemotherapy treatment. Additional clinical trials are needed to confirm these findings and establish the optimal order for multidrug treatment of mCRPC.

CASTRATION-RESISTANT PROSTATE CANCER: NEW PERSPECTIVES IN PHARMACOLOGICAL TREATMENT

2019 ◽  
Vol 25 (1) ◽  
pp. 49-58
Author(s):  
Dmitry A. Andreev ◽  
A. A Zavyalov ◽  
A. V Govorov ◽  
K. A. Kokushkin ◽  
M. Y Davidovskaya
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Treatment Options ◽  
Specific Treatment ◽  
Cochrane Library ◽  
Cancer Drug ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequence ◽  
Treatment Algorithms ◽  
Castration Resistant

Prostate cancer remains one of the most actual problems in oncourology due to its high prevalence and resistance to therapy. Within 5 years of active treatment and follow-up, the castration-resistant prostate cancer (CRPC) develops in 10-20% of patients. This type of disease course resists treatments and leads to death. Medical resources distinguish two different forms of CRPC: non-metastatic and metastatic. Such separation is critically important because each of two forms requires different treatment algorithms. This paper summarizes the main outlines of foreign clinical guidelines and reviews the new treatment options for non-metastatic and metastatic CRPC as wells as the design and results of key clinical trials on drug efficiency. To prepare the review, the comprehensive literature search was conducted using PubMed/Medline, the Cochrane Library, EMBASE, CyberLeninka, e-library databases. The search line included phrases containing the following words: prostate cancer, castration-resistant prostate cancer, drug therapy, treatment algorithms, clinical studies, etc. In accordance to foreign guidelines, it is essential to determine the high risk patients with non-metastatic CRPC and promptly apply new therapeutic options including apalutamide and enzalutamide, which have proven being effective in clinical trials as therapies that attenuate the transition of the non-metastatic CRPC to the metastatic stage. Foreign medical guidelines propose to apply a wider set of treatment algorithms for patients with metastatic CRPC, for instance: considerations on possibilities to use the cabazitaxel instead of docetaxel in the 1st line therapy in patients with pre-existing mild peripheral neuropathy, etc. as well as new therapies - pembrolizumab and sipuleucel-T. The issues regarding the selection of patients with CRPC for specific treatment algorithms and defining the optimal sequence of therapeutic regimens as well as combining various regimens with minimizing toxic effects and maximizing patient benefits remain unsolved.

ARCHES: Efficacy of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5048-5048
Author(s):  
Andrew J. Armstrong ◽  
Russell Zelig Szmulewitz ◽  
Daniel Peter Petrylak ◽  
Jeffrey M. Holzbeierlein ◽  
Arnauld Villers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Progression Free Survival ◽  
High Volume ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Prior Therapy ◽  
Castration Resistant ◽  
Secondary Endpoints ◽  
Grade 3

5048 Background: ENZA has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). ARCHES assessed the efficacy of ENZA with ADT in men with mHSPC, including pre-specified subgroups based on prior therapy. Methods: ARCHES, a multinational, double-blind, Phase 3 study (NCT02677896), randomized patients (pts) with mHSPC 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel (doce) use. Primary endpoint was radiographic progression-free survival (rPFS; centrally assessed radiographic progression or death within 24 weeks of treatment discontinuation). Secondary endpoints included time to initiation of new antineoplastic therapy and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Results: 1150 men were randomized to ENZA (n = 574) or PBO (n = 576). Overall, 63% had high-volume disease, 18% had prior doce, and 91% had prior ADT or orchiectomy (orch). Median follow-up was 14.4 mo. ENZA + ADT significantly improved rPFS (Table); significant improvements in rPFS were also reported in prior treatment subgroups. Secondary endpoints improved with ENZA + ADT (Table), with no significant impact in time to deterioration in urinary symptoms. OS data are immature. Grade 3–4 adverse events (AEs) were reported in 23.6% of ENZA pts vs. 24.7% of PBO pts with no unexpected AEs. Conclusions: ENZA + ADT significantly improved rPFS and other efficacy endpoints vs. PBO + ADT in men with mHSPC. Preliminary safety analysis appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Clinical trial information: NCT02677896. [Table: see text]

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