CHAARTED was an ECOG-led phase III trial looking at early chemotherapy with the use of docetaxel in addition to androgen deprivation therapy (ADT) versus ADT alone in hormone-sensitive prostate cancer. The positive results of the trial showing marked improvement in overall survival in those who received chemotherapy with ADT have revolutionized the treatment of metastatic castration-sensitive prostate cancer. In addition to overall survival, secondary endpoints such as time to castration resistance, PSA response were also significant for the patients who received early chemotherapy.

Male ; Humans ; Prostatic Neoplasms/pathology* ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Hormones ; Androgen Antagonists/therapeutic use*

ARAMIS is an international Phase III trial demonstrating the beneficial role of darolutamide, a novel anti-androgen that has been found to prolong metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer. Darolutamide is a novel nonsteroidal androgen receptor antagonist that has unique structurally distinct properties with low blood–brain barrier penetration that was shown to improve metastasis-free survival by 22 months compared to placebo (40.4 months vs 18.4 months), reducing the risk of metastasis or death by 59%. Darolutamide also showed improvement in secondary and exploratory endpoints including progression-free survival, prolonged time to PSA progression, PSA response and time to initiating additional antineoplastic therapy, time to pain progression, and time to cytotoxic chemotherapy, but overall survival is not yet reached in either the darolutamide or the placebo arm. Adverse events leading to trial discontinuation were similar at 8.9% and 8.7% in the darolutamide and placebo arms, respectively. Darolutamide was filed as a new drug application to the United States Food and Drug Administration (US FDA) for use in the setting of nonmetastatic castration-resistant prostate cancer.
Androgen Receptor Antagonists ; Androgens ; Humans ; Male ; Prostatic Neoplasms, Castration-Resistant ; Pyrazoles

The last decade has seen remarkable advances in the treatment of prostate cancer. Until 2010, only docetaxel had demonstrated the ability to improve the survival in metastatic castration-resistant prostate cancer (mCRPC). While effective, many men were reluctant to get treatment with docetaxel because of the perceived toxicity, thereby further limiting the benefit of the one available and effective therapy. Remarkably, within the last 8 years, the field has seen a multitude of therapies that demonstrate an ability to extend survival for men with prostate cancer. Abiraterone and enzalutamide demonstrated the importance of the androgen axis in propelling prostate cancer growth. Sipuleucel-T was immunotherapy's entry into the evolving prostate cancer armamentarium, as the therapeutic cancer vaccine established an ability to extend survival despite an apparent lack of short-term effect on progression-free survival and prostate-specific antigen (PSA). Radium-223 built on the palliative success of previous radiopharmaceuticals, but this alpha-emitting agent importantly had limited hematologic-related toxicity and was associated with a survival advantage, unlike its in-class predecessors. Cabazitaxel also emerged as a second-line chemotherapy option in patients who had already progressed on docetaxel.
Antineoplastic Agents/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Humans ; Male ; Molecular Targeted Therapy ; Prostatic Neoplasms/drug therapy*

Signaling through the vitamin D receptor has been shown to be biologically active and important in a number of preclinical studies in prostate and other cancers. Epidemiologic data also indicate that vitamin D signaling may be important in the cause and prognosis of prostate and other cancers. These data indicate that perturbation of vitamin D signaling may be a target for the prevention and treatment of prostate cancer. Large studies of vitamin D supplementation will be required to determine whether these observations can be translated into prevention strategies. This paper reviews the available data in the use of vitamin D compounds in the treatment of prostate cancer. Clinical data are limited which support the use of vitamin D compounds in the management of men with prostate cancer. However, clinical trials guided by existing preclinical data are limited.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Calcifediol/blood* ; Calcitriol/therapeutic use* ; Clinical Trials as Topic ; Ergocalciferols/therapeutic use* ; Humans ; Male ; Prostatic Neoplasms/prevention & control* ; Signal Transduction ; Vitamin D/metabolism* ; Vitamin D Deficiency/epidemiology*

PROSPER is an international Phase III trial demonstrating the beneficial role of enzalutamide, an androgen receptor antagonist, in prolonging metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer. The trial showed that the median metastasis-free survival was 21.9 months longer for those treated with enzalutamide (36.6 months) compared to those treated with placebo (14.7 months). Enzalutamide also showed prolonged time to PSA progression, PSA response, and time to initiating additional antineoplastic therapy although overall survival is not yet reached. Enzalutamide is the second antiandrogen (next to apalutamide) that has gained the United States Food and Drug Administration (US FDA) label indication for use in the setting of nonmetastatic castration-resistant prostate cancer.
Androgen Antagonists/therapeutic use* ; Antineoplastic Agents/therapeutic use* ; Benzamides ; Humans ; Male ; Nitriles ; Phenylthiohydantoin/therapeutic use* ; Prostatic Neoplasms, Castration-Resistant/drug therapy*

Chemotherapy in prostate cancer (PCa) has undergone dramatic landscape changes. While earlier studies utilized varying chemotherapy regimens which were found to be largely palliative in nature and hardly resulted in durable or meaningful responses, docetaxel resulted in the first chemotherapy agent that showed improvement in overall survival in metastatic castration-resistant prostate cancer (mCRPC). However, combination chemotherapy or any agents added to docetaxel have failed to yield incremental benefits. The improvement in overall survival as well as secondary endpoints of prostate-specific antigen (PSA) and time to recurrence when using docetaxel in the metastatic hormone-sensitive state has changed the standard of care for treatment of newly diagnosed de novo metastatic PCa. There are also promising results in locally advanced PCa and high-risk PCa in both the neoadjuvant and adjuvant settings. This review summarizes the historical as well as the more contemporary use of chemotherapeutic agents in PCa in varying states and phases of disease.
Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemotherapy, Adjuvant ; Docetaxel/therapeutic use* ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Neoadjuvant Therapy ; Prostatic Neoplasms/surgery* ; Taxoids/therapeutic use*