Superior Anti-tumor Efficacy of Bicalutamide 80 mg in Combination with a Luteinizing Hormone-releasing Hormone (LHRH) Agonist Versus LHRH Agonist Monotherapy as First-line Treatment for Advanced Prostate Cancer: Interim Results of a Randomized Study in Japanese Patients

Akaza, Hideyuki; Yamaguchi, Akito; Matsuda, Tadashi; Igawa, Mikio; Kumon, Hiromi; Soeda, Asaki; Arai, Yoichi; Usami, Michiyuki; Naito, Seiji; Kanetake, Hiroshi; Ohashi, Yasuo

doi:10.1093/jjco/hyh001

Cited by 77 publications

(73 citation statements)

References 12 publications

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“…[27][28][29][30] Furthermore, an established 5-R inhibitor such as finasteride can reduce intraprostatic levels of DHT. 31 Finasteride prevents or delays the appearance of prostate cancer, 32 although it can increase the detection of high-grade cancer.…”

Section: Discussionmentioning

confidence: 99%

Importance of the intracrine metabolism of adrenal androgens in androgen-dependent prostate cancer

Suzuki

Nishiyama

Hara

et al. 2007

Prostate Cancer Prostatic Dis

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The metabolic pathways of androgens and processes by which androgens induce re-growth after androgen deprivation therapy in prostate cancer have not been fully elucidated. In this study, finasteride decreased PSA secretion in medium containing testosterone, androstenedione, androstenediol and dehydroepiandrosterone, whereas dihydrotestosterone (DHT)-and hydroxyflutamide-induced PSA production was not inhibited by finasteride in LNCaP-FGC cells. The present data show that adrenal androgen precursors do not directly interact with androgen receptors (ARs) but are converted to DHT via the intraprostatic metabolic pathways, resulting in the induction of LNCaP activity. This is the first report confirming this mechanism experimentally and also suggest the use of combined therapies that target ARs and prevent the formation of DHT within prostate cancer cells to achieve optimal therapeutic efficacy.

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Section: Discussionmentioning

confidence: 99%

Importance of the intracrine metabolism of adrenal androgens in androgen-dependent prostate cancer

Suzuki

Nishiyama

Hara

et al. 2007

Prostate Cancer Prostatic Dis

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“…Some recent studies have shown better outcomes in patients treated with CAB compared with LHRH agonist monotherapy. [28][29][30] However, a metaanalysis and randomized placebo-controlled clinical trial have revealed that the difference between LHRH agonist and CAB was only of a few percentage or nothing. 31,32 Therefore, the initial treatment strategy within the present step-up for hormonal therapy may be reasonable in clinical settings.…”

Section: 9%mentioning

confidence: 99%

Impact of pretreatment factors, biopsy Gleason grade volume indices and post-treatment nadir PSA on overall survival in patients with metastatic prostate cancer treated with step-up hormonal therapy

Miyamoto

Ito

Miyakubo

et al. 2011

Prostate Cancer Prostatic Dis

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BACKGROUND:In the era when various treatment agents for advanced-stage prostate cancer are available, it is important to investigate overall survival for metastatic prostate cancer treated with step-up hormonal treatment as a reference against new treatment regimens, including antitumor agents and/or new hormonal derivatives, and it is desirable to explore pretreatment, biopsy-related and post-treatment prognostic factors to establish tailor-made treatment strategies. METHODS:Between 1992 and 2002, 94 patients were diagnosed with prostate cancer with distant metastases in our facility. Various pretreatment clinical findings including serum PSA, testosterone, alkaline phosphatase (ALP), digital rectal examination (DRE) and extension of disease score were investigated for predicting outcomes in step-up hormonal treatment. We also investigated the impact of pathological findings including Gleason grading, tumor volume indices, various Gleason grade 5 volume indices in biopsy specimens, and post-treatment PSA nadir following step-up hormonal treatment on overall survival. RESULTS:The 3-and 5-year overall survival was 72.4% and 62.5%, respectively. According to univariate analyses, patients with PSA p100 ng ml -1 , ALP o440 IU l -1 , T1c to T3 on DRE, extension of disease (EOD) score 0-3, no Gleason grade 5 cancer in biopsy specimens or less such cancer and good response at any stage of hormonal therapy had significantly better overall survival than did patients with alternative status. A multivariate Cox proportional hazard model revealed that PSA nadir after first-line hormonal treatment, PSA nadir after second-line treatment and Gleason grade 5 volume index were independent prognostic factors.CONCLUSIONS: Even in very advanced prostate cancer, local pathological indices, a Gleason grade 5 volume index in particular, could differentiate patients with better prognosis from worse prognosis.Step-up hormonal therapy including luteinizing hormone-releasing hormone agonist, estrogen derivatives and steroid hormones may be valuable in patients with metastatic prostate cancer, especially in good responders at any stage of hormonal therapy.

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“…Later on, the guidelines have been revised to clearly recommend 'consideration of MAB using bicalutamide' on the basis of one randomized clinical trial and one analytical research study [51][52][53]. The data quoted for the 2006 ASCO guidelines are results of interim analysis [53] (median follow-up of 66 weeks) of a multicenter, randomized, placebocontrolled phase III study comparing MAB group using bicalutamide and GnRH-A alone group for 205 Japanese patients with untreated advanced prostate cancer.…”

Section: A Combined Androgen Blockadementioning

confidence: 99%

“…The data quoted for the 2006 ASCO guidelines are results of interim analysis [53] (median follow-up of 66 weeks) of a multicenter, randomized, placebocontrolled phase III study comparing MAB group using bicalutamide and GnRH-A alone group for 205 Japanese patients with untreated advanced prostate cancer. Patients received an LHRH agonist and were randomly assigned to bicalutamide 80 mg orally once daily or placebo.…”

Section: A Combined Androgen Blockadementioning

confidence: 99%

Current Medical and Surgical Options for Androgen Deprivation in Prostate Cancer Patients

Bayraktar¹,

A²

2010

TOPCANJ

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Abstract:The growth of prostate cancer cells is driven by androgens. Thus, androgen deprivation, is one of the main treatment modalities in the management of prostate cancer. Historically, bilateral orchiectomy, which achieves 95% reduction of testosterone levels within 3 hours, was the only effective androgen deprivation therapy (ADT). In the 1980s, luteinizing hormone-releasing hormone agonists (LHRH-A) were introduced to reduce testosterone to castration levels. After the 1980s, nonsteroidal antiandrogens were developed in addition to steroidal antiandrogens. Since then, so-called maximum androgen blockade (MAB)/combined androgen blockade (CAB), which is a combination of surgical or medical castration and oral antiandrogens, has been suggested. More recently, novel treatment modalities have been developed, such as intermittent androgen suppression (IAS), nonsteroidal antiandrogen monotherapy, and alternative antiandrogen therapy after relapse from the initial MAB/CAB. ADT, whether surgical or medical, provides important quality of life (QOL) benefits in patients with advanced and metastatic prostate cancer. While the principle of the therapy has remained unchanged, the role, type and timing of these therapies is continuously evolving. This review will focus on the current medical and surgical options for ADT in advanced and metastatic prostate cancer, summarizing the results of several recent clinical trials and discuss their implications for clinical practice and for future research in this disease.

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Superior Anti-tumor Efficacy of Bicalutamide 80 mg in Combination with a Luteinizing Hormone-releasing Hormone (LHRH) Agonist Versus LHRH Agonist Monotherapy as First-line Treatment for Advanced Prostate Cancer: Interim Results of a Randomized Study in Japanese Patients

Cited by 77 publications

References 12 publications

Importance of the intracrine metabolism of adrenal androgens in androgen-dependent prostate cancer

Importance of the intracrine metabolism of adrenal androgens in androgen-dependent prostate cancer

Impact of pretreatment factors, biopsy Gleason grade volume indices and post-treatment nadir PSA on overall survival in patients with metastatic prostate cancer treated with step-up hormonal therapy

Current Medical and Surgical Options for Androgen Deprivation in Prostate Cancer Patients

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