Emerging Therapies in Metastatic Prostate Cancer.

PURPOSE OF REVIEW: In the last decade, there have been multiple landmark therapeutic advances for the treatment of metastatic prostate cancer, both in the castration-resistant and hormone-sensitive setting. In this review, we highlight recent progress and ongoing trials for metastatic prostate cancer, including advances in chemotherapy, androgen receptor-directed therapy, targeted therapies, and immunotherapy. RECENT FINDINGS: Several landmark studies for men with metastatic hormone-sensitive prostate cancer demonstrated improvement in overall survival with the addition of docetaxel chemotherapy or abiraterone acetate to standard androgen deprivation therapy. A single-arm phase 2 study of the PARP inhibitor olaparib demonstrated high response rates and more favorable progression-free and overall survival for men with metastatic castration-resistant prostate cancer and DNA repair defects treated with olaparib compared with men without DNA repair defects. Multiple ongoing clinical trials are investigating novel hormonal therapies and combinations of chemotherapy, targeted small molecules, immunotherapy, and radiopharmaceuticals. Progress continues to be made in the treatment of metastatic prostate cancer, and ongoing clinical trials continue to investigate novel agents and approaches to treatment.

Osteoclast inhibitor treatment among men with metastatic castration-resistant prostate cancer.

BACKGROUND: National Comprehensive Cancer Network guidelines recommend monthly osteoclast inhibitor treatment (OIT) in men with metastatic castration-resistant prostate cancer (mCRPC) to prevent skeletal related events (SREs). We assessed adherence to guidelines by quantifying treatment for SRE prevention in a population-based cohort of men with mCRPC. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified men aged >65 with prostate cancer as a primary cause of death during 2006-2010. We assessed OIT during a 12-month period between 15 and 3 months before death and used multivariable negative binomial regression to identify factors associated with treatment. RESULTS: Among 9,634 men who died of prostate cancer, 22% received ≥ 1 OIT, and use increased slightly over time. Men age 75-84 and ≥ 85 were less likely than younger men to be treated (IRR 0.63, 95% CI 0.49-0.78 and IRR 0.34, 95% CI 0.17-0.50, respectively). African American men were less likely than white men to receive OIT (IRR 0.75, 95% CI 0.54-0.95), as were men from areas with lower median income (P=0.014). Compared with men seeing a urologist only, men seeing a medical oncologist and a urologist (IRR 2.52, 95% CI 2.36-2.68) or a medical oncologist alone (IRR 3.82, 95% CI 3.54-4.09) had higher incidence rates of treatment. CONCLUSIONS: Fewer than a quarter of American men dying of prostate cancer received recommended treatment to prevent SREs within the final year of their lives, with particularly low rates of treatment among older men, African American men, and those living in areas with low median income. Visits with a medical oncologist were associated with increased use. Further evaluation of these disparities by age, race and socioeconomic status are necessary to identify interventions to reduce them.

Epigenetic Targeting of Platinum Resistant Testicular Cancer.

The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, little is known of the epigenetic alterations in testicular cancer and particularly in platinum refractory germ cell tumors. Germ cell derived testicular cancers, as compared to somatic tumors, appear to have a unique epigenetic profile that features more extensive DNA hypomethylation. Emerging data from clinical specimens suggest that epigenetic aberrations, especially DNA hypermethylation, can contribute to chemotherapy resistance and poor clinical outcomes in testicular germ cell tumors. Recent data indicate that testicular cancer cells, even those resistant to platinum, are highly sensitive to low doses of demethylating agents. Based on these promising preclinical studies, we suggest that DNA methylation inhibitors in combination with chemotherapeutic agents may offer a path to overcome acquired drug resistance in testicular cancer, laying the foundation and rationale for testing this class of epigenetic drugs in the clinical setting. In this mini-review we provide a brief overview of the promise of DNA methylation therapy to treat patients with refractory cancer of the testes.