Xtandi is often referred to as a “super bicalutamide (Casodex).” Casodex functions as a androgen blockade, which deters testosterone from being able to interact with the prostate cancer cell and feed the growth of the cancer.

There are some oncologists in the United States and the standard hormone treatment in Europe often utilizes Casodex as mono-therapy thereby preserving a better quality of life in men with advanced prostate cancer which is still hormone responsive. However, the efficacy as a monotherapy with Casodex has been shown to be limited.

Xtandi, which like Casodex, is an oral androgen receptor (AR) inhibitor but with higher AR–binding affinity vs Bic, it prevents nuclear translocation, shows no DNA binding, and induces apoptosis of prostate cancer tumors. The FDA in the US approved Xtandi after prolonging overall survival in post-docetaxel metastatic castration resistant prostate cancer.

In a phase 2 study that assessed Xtandi as a monotherapy in men with hormone responsive and non-castrate testosterone (T) ?230 ng/dL Xtandi achieved a high PSA response rate and marked PSA decline with efficacy similar to castration. In contrast to the more traditional hormonal castration therapy (ADT), body mass index remained stable and metabolic variables (fat body mass, lipid and glycemic profiles) were not substantially impacted over the 6 month study period.

In the trial men with any stage of hormone responsive prostate cancer (ECOG PS 0, life expectancy >1 y) requiring hormonal therapy received Xtandi 160 mg/d for 25 wks.

Primary endpoint was PSA response (?80% decline at wk 25). Other endpoints were endocrine levels, pharmacokinetics, safety, and metabolic changes (body composition, bone biomarkers, lipids, and glycemic profiles).

Sixty seven (67) men were enrolled in the trial. Median age was 73 y; 39% had metastases, 36% and 24% had prior prostatectomy and radiation, respectively. Xtandi levels reached steady state after ~4 wks.

Mean changes in metabolic outcomes at week 25 included: –0.24% total body bone mineral density (BMD), –4.15% lean body mass, 6.85% fat body mass, 14.75% bone alkaline phosphatase, 4.55% total cholesterol, 6.48% triglycerides, –1.98% A1c, –0.10% fasting glucose, and 45.06% HOMA-IR. At wk 25, PSA response was 93% (62/67; 95% CI, 86%–99%); median PSA decrease was –99.6%.

Mean levels of testosterone and estrogen increased 114% and 72%, respectively; other endocrine increases were observed, the highest was 185% for luteinizing hormone.

Most common treatment side effects were grade 1 and included gynecomastia (36%), fatigue (34%), nipple pain (19%), and hot flush (18%). Five pts had serious side effects that were not drug related.

This trial demonstrates the high probability that Xtandi when used with men with hormone responsive advanced prostate cancer could achieve prostate cancer control with less negative side effects than our current mehods of using hormone therapy. Perhaps, it might become a kinder and gentler form of hormone therapy for men with advanced prostate cancer.

J Clin Oncol 31, 2013 (suppl; abstr 5001)
Author(s): Matthew Raymond Smith, Michael Borre, Per Rathenborg, Patrick Werbrouck, Hendrik Van Poppel, Axel Heidenreich, Peter Iversen, Edwina Baskin-Bey, Frank Perabo, De Phung, Bertrand Tombal; Departments of Hematology and Oncology, Massachusetts General Hospital Cancer Center, Boston, MA; Department of Urology, Århus University Hospital, Skejby, Denmark; Department of Urology, Herlev Hospital, Herlev, Denmark; Department of Urology, AZ Groeninge Kortrijk, Kortrijk, Belgium; Department of Urology, University Hospitals Leuven, Leuven, Belgium; Department of Urology, RWTH University, Aachen, Germany; Department of Urologuy, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Astellas Pharma Global Development, Inc., Staines, United Kingdom; Astellas Pharma Global Development, Inc., Leiderdorp, Netherlands; Department of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium

Joel T. Nowak, M.A., M.S.W.