Abstract
Historically, androgen-deprivation therapy (ADT) was the only primary treatment for metastatic prostate cancer. After prostate cancer develops into castration-resistant prostate cancer (CRPC), there are a few life-prolonging drugs, including taxanes, such as docetaxel and cabazitaxel, as well as novel androgen receptor-targeting agents, such as abiraterone acetate and enzalutamide, which have been proved in clinical trials. However, the prognosis of men with CRPC is still poor. The duration from initiation of ADT to CRPC has not improved in recent decades because no novel therapeutic options have emerged. However, recently, up-front docetaxel chemotherapy has been shown to prolong progression-free as well as overall survival in men with metastatic hormone-naïve prostate cancer. This offers a new way to expand the role of chemotherapy for hormone-naïve prostate cancer. In this review, we summarize the proof-of-concept as well as the current status of taxane chemotherapy for hormone-naïve prostate cancer, focusing on phase 3 clinical trials investigating oncological outcome, and discuss the future direction in this field.
Highlights
Hormonal therapy such as androgen-deprivation therapy (ADT) using surgical or pharmacological castration and/or antiandrogens was the only gold standard for therapy of metastatic prostate cancer
The expression of epithelial marker E-cadherin was downregulated in docetaxel-resistant cells [8]. These results suggest docetaxel resistance in highly metastatic prostate cancer with a high level of epithelial–mesenchymal transition, supporting the superior anticancer effect of docetaxel chemotherapy for non-metastatic hormone-naïve prostate cancer compared with metastatic prostate cancer
It has recently been reported that only 4.4% of castration-resistant prostate cancer (CRPC) patients in the US received androgen receptor (AR)-targeting agents and cabazitaxel in addition to docetaxel chemotherapy [14]; achieving sufficient use of therapeutics for CRPC would be difficult, which may compromise the merit of novel agents
Summary
Hormonal therapy such as androgen-deprivation therapy (ADT) using surgical or pharmacological castration and/or antiandrogens was the only gold standard for therapy of metastatic prostate cancer. In line with this notion, we have recently shown cross-resistance to docetaxel in CRPC cells, but not vice versa using an LNCaP cell model [6] These results provide proof-of-concept for possible superior anticancer activity of up-front taxane chemotherapy for hormone-naïve prostate cancer, compared with traditional ADT followed by docetaxel chemotherapy. The results of the French GETUG-AFU-15 study were reported in 2013 It did not show any improvement of OS by combining docetaxel chemotherapy with ADT for metastatic hormone-naïve prostate cancer, docetaxel chemotherapy did improve progression-free survival (PFS) [9]. One study failed, but two others showed significant improvement with up-front docetaxel administration for metastatic hormone-naïve prostate cancer, all three studies were conducted with similar concept and design Why did those trials report controversial results? OS, overall survival; PFS, progression-free survival; RP, radical prostatectomy; RT, radiotherapy
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