Effectiveness and adverse effects of hormonal therapy for prostate cancer: Japanese experience and perspective

Abstract

Recently, novel anti-androgens and inhibitors of androgen biosynthesis have been developed through the elucidation of mechanisms of castration resistance of prostate cancer. We believe that these new developments will improve hormonal therapy. On the other hand, there has been an increase in criticism of hormonal therapy, because hormonal therapy is supposed to induce adverse effects such as cardiovascular disease. In this review, we have introduced the Japanese experience of hormonal therapy, because we believe that there may be ethnic differences between Caucasians and Asian people in the efficacy and adverse effects of hormonal therapy. First, we showed that primary hormonal therapy can achieve long-term control of localized prostate cancer in some cases and that quality of life of patients receiving hormonal therapy is rather better than previously thought. Neoadjuvant and adjuvant hormonal therapy in cases undergoing radical prostatectomy or radiotherapy are very useful for high-risk or locally advanced prostate cancer. Further clinical trials are required to confirm the efficacy of neoadjuvant or adjuvant hormonal therapy. We showed that the death from cardiovascular diseases in Japanese patients receiving hormonal therapy was not higher than that in the general population. However, efforts should be made to decrease the adverse effects of hormonal therapy, because life-style change may increase the susceptibility to adverse effects by hormonal therapy even in Japan. Managements of endocrine and metabolic dysfunction, such as diabetes mellitus, are essential. New hormonal compounds such as selective androgen receptor modulators capable of specifically targeting prostate cancer are expected to be developed.

No increased risk of coronary heart disease for patients receiving androgen deprivation therapy for prostate cancer in Chinese/Taiwanese men

“…One review study by Namiki et al . () reported that deaths from cardiovascular diseases in Japanese patients receiving hormonal therapy were not higher than those of the general population. They indicated that ethnic differences exist on the adverse effects of hormonal therapy in PC patients.…”

Phase‐1 study of abiraterone acetate in chemotherapy‐naïve Japanese patients with castration‐resistant prostate cancer

“…Consistent with this, testosterone levels in prostate cancer tissues remain elevated after castration (approximately 25% of precastration levels) even though serum testosterone levels are lowered to <50 ng/dL by inhibiting gonadal androgen synthesis with ADT treatment (surgical or medical castration) . Therefore, treatment with agents that block testosterone production in the adrenal glands and tumor cells is warranted to mitigate tumor cell proliferation after surgical or medical castration using luteinizing hormone‐releasing hormone (LHRH) analogs …”

“…Because ethnic diversities between Caucasians and Asians could influence the effectiveness of treatment, as well as the types of and susceptibility to adverse effects, studies validating clinical benefits of AA in CRPC patients of different ethnic backgrounds are encouraged. (10) Prior to the present study, with no clinical experience of this drug in Japanese patients, the recommended dose for AA in Japanese CRPC patients had not been established. The objective of the current phase-I study was to evaluate pharmacokinetics, pharmacodynamics, and preliminary efficacy and safety of AA in Japanese CRPC patients.…”

“…In global studies, AA has been extensively studied in the USA and EU populations. Because ethnic diversities between Caucasians and Asians could influence the effectiveness of treatment, as well as the types of and susceptibility to adverse effects, studies validating clinical benefits of AA in CRPC patients of different ethnic backgrounds are encouraged . Prior to the present study, with no clinical experience of this drug in Japanese patients, the recommended dose for AA in Japanese CRPC patients had not been established.…”

“…(8,9) Therefore, treatment with agents that block testosterone production in the adrenal glands and tumor cells is warranted to mitigate tumor cell proliferation after surgical or medical castration using luteinizing hormone-releasing hormone (LHRH) analogs. (10) Abiraterone acetate (AA) is an orally active prodrug of abiraterone. Abiraterone irreversibly inhibits cytochrome P450 17a-hydroxylase and C17, 20-lyase enzymes responsible for adrenal, testicular and intratumoral androgen synthesis.…”