Short-term enzalutamide treatment for the potential remission of active surveillance or intermediate-risk prostate cancer: a case study, review, and the need for a clinical trial

Abstract

Active surveillance (AS) is a widely recognized and utilized option by which prostate cancer patients with less aggressive tumors on diagnosis defer immediate traditional conventional therapy (surgery, radiation) and undergo close monitoring by a physician for any clinical or pathologic changes. The juxtaposition of low- to intermediate-risk elderly patients between effective and conventional treatment with associated risks and monitoring without the opportunity for relief of anxiety and other psychological problems can be significant. Minimal and safe treatment over 6 months with the hope of eliminating the existing disease is of significant interest to prostate cancer patients. Unfortunately, dietary supplements have failed to improve and have sometimes even contributed to disease progression. In addition, the use of multiple medications is not always appropriate or safe. In this case study, we administered low doses of enzalutamide (80 mg/day–120 mg/day) in an AS patient during a 6 month period. Results showed a significant reduction in tumor size, as evidenced by magnetic resonance imaging and color Doppler, as well as a an undetectable level of prostate specific antigen during, and immediately following treatment. The use of an oral second-generation androgen-receptor signaling inhibitor was shown to be of benefit to patients unwilling to pursue AS and conventional treatment. Administration of enzalutamide did not reduce testosterone levels, but helped maintain good quality of life, was more cost effective at low doses, and was previously shown to be heart healthy and efficacious during early stages of castration-resistant prostate cancer. Although we do not advocate enzalutamide as a treatment approach in these situations, we believe that a clinical trial to evaluate short-term low-dose treatment using enzalutamide is warranted.

A feasibility study of the therapeutic response and durability of short-term androgen targeted therapy in early prostate cancer managed by surveillance: The Therapeutics in Active Prostate Surveillance (TAPS01) study

“…However, this was given as long-term therapy and predates the modern AS era, in which the clinically important endpoint is not survival but avoiding active treatment for disease progression [1,2,5]. Interest in this area has now re-emerged with a better understanding of disease prognosis, the acceptance of AS for mainstream management, and better selective ATT drugs [19]. The ENACT study, for example, has treated men on AS with enzalutamide (NCT02799745) or placebo.…”

“…However, concerns that long-term androgen therapy may induce tumour adaptation have so far reduced enthusiasm for adopting 5ARI or other androgen-targeted therapy (ATT) in routine practice [18]. By contrast, short-term ATT may have the desired specific antitumour effects without the risk of longer-term tumour adaptation [19][20][21].…”