Intermittent Androgen Blockade in Prostate Cancer: Rationale and Clinical Experience

Wolff, J. M.; Tunn, U. W.

doi:10.1159/000020310

Cited by 20 publications

(13 citation statements)

References 23 publications

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“…It has been hypothesized that androgen ablation, which causes regression of androgen-dependent prostate cancer, may inadvertently select those cancerous cells that can grow independently of androgen through various mechanisms (2). To overcome this, it has been proposed that intermittent androgen ablation may delay the development of prostate tumors that are refractory to androgen ablation (44,45). Indeed, it has been reported that intermittent androgen therapy reverts androgen-independent prostate cancer to androgenstimulated phenotype in mice (46) and has been found to improve patient survival in clinic (45).…”

Section: Discussionmentioning

confidence: 99%

“…To overcome this, it has been proposed that intermittent androgen ablation may delay the development of prostate tumors that are refractory to androgen ablation (44,45). Indeed, it has been reported that intermittent androgen therapy reverts androgen-independent prostate cancer to androgenstimulated phenotype in mice (46) and has been found to improve patient survival in clinic (45). However, cautions should be taken during the intermittent androgen therapy.…”

Section: Discussionmentioning

confidence: 99%

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Androgen via p21 Inhibits Tumor Necrosis Factor α-induced JNK Activation and Apoptosis

Tang

Kokontis

Lin

et al. 2009

Journal of Biological Chemistry

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The male hormone androgen is a growth/survival factor for its target tissues or organs. Yet, the underlying mechanism is incompletely understood. Here, we report that androgen via p21 inhibits tumor necrosis factor ␣-induced JNK activation and apoptosis. Inhibition by androgen requires the transcription activity of androgen receptor (AR) and de novo protein synthesis. Androgen⅐AR induces expression of p21 that in turn inhibits tumor necrosis factor ␣-induced JNK and apoptosis. Furthermore, genetic interruption of p21 alleles abolishes the inhibition by androgen. Our results reveal a novel cross-talk between androgen⅐AR and JNK, thereby providing a molecular mechanism underlying the survival function of androgen.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Androgen via p21 Inhibits Tumor Necrosis Factor α-induced JNK Activation and Apoptosis

Tang

Kokontis

Lin

et al. 2009

Journal of Biological Chemistry

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“…The mean T level did not change between baseline and the end of the six successive OTPs while the mean duration of the OTPs shortened progressively. However the impact on this intermittent treatment modality on the quality of life and on the life expectancy of patients remain to be proven and are the purpose on ongoing randomized trials [23,24] .…”

Section: Discussionmentioning

confidence: 99%

Intermittent Androgen Castration: A Biological Reality during Intermittent Treatment in Metastatic Prostate Cancer?

Mottet

Lucas

Sene³

et al. 2005

Urol Int

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Introduction: To assess the effects of intermittent maximal androgen blockade (IMAB) on testosterone (T) levels during on- and off-treatment periods. Materials and Methods: A total of 51 patients with metastatic prostate cancer underwent a 6-months period of continuous maximal androgen blockade (MAB) consisting of leuprorelin (3.75 mg at monthly intervals) plus flutamide (250 mg t.i.d.) followed by IMAB. During each cycle, the cut-off prostate-specific antigen (PSA) levels to stop and resume treatment were 4 and 10 ng/ml, respectively. IMAB continued until progression under treatment occurred. Monthly PSA and T measurements were performed in central laboratories. Results: From the 51 patients included (mean age 67.6 years), 27, 16, 12, 8 and 5 underwent a second, third, fourth, fifth and sixth cycle, respectively (mean follow up: 17 months). Before treatment, 4 patients had a T lower than normal laboratory value but these recovered all to a normal T value at the end of the first cycle. During the 6 cycles, only 8 patients did not recover a normal T at least once during the off-treatment periods (OTP). The mean T values at the end of each OTP did not change during these 6 cycles (Anova test, p = 0.621) with a mean stable recovery delay of 32–43 days (Anova test, p = 0.722). Conclusion: IMAB protocol with an initial 6-month treatment period can result in an intermittent castration with the recovery of normal T levels in most patients during six consecutive cycles of treatment.

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“…Experimental and preclinical models of prostate cancer [32,33] have provided compelling evidence that allowing testosterone recovery after a period of androgen deprivation would help prevent the development of resistance by lessening the selection pressure for tumour growth in low‐androgen conditions. By cycling of reversible androgen suppression, there appears to be recovery of apoptosis and subsequent slower progression to an androgen‐independent state, thereby providing the rationale for intermittent ADT [34,35]. The potential advantages of intermittent ADT over continuous ADT are a prolonged period of androgen dependence, a decrease in the cost of care and improved health‐related quality of life through a reduction in ADT‐associated adverse effects during off‐treatment phases.…”

Section: Intermittent Adtmentioning

confidence: 99%

Landmarks in hormonal therapy for prostate cancer

Hammerer

Madersbacher

2012

BJU International

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• It is >70 years since the responsiveness of symptomatic metastatic prostate cancer to androgen deprivation was first demonstrated. • Since those pivotal studies, progress in hormonal therapy of prostate cancer has been marked by several important developments and the availability of various androgen-suppressing agents. • Treatment guidelines have continued to evolve with clinical and therapeutic progress, but androgen-deprivation therapy (ADT) remains the standard of care for non-localised prostate cancer. • Because of the long-term experience (>20 years) and wealth of evidence from the large number of clinical trials, the luteinizing hormone-releasing hormone (LHRH) agonists are currently the main forms of ADT. • Treatment strategies should be adapted to the individual patient in terms of timing, duration and choice of agent. • Prostate cancer remains the most common type of cancer in men and the development of castration-resistant disease seems inevitable, which together drive the clear and continuing need for new, effective agents for ADT to be used alongside the LHRH agonists.

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Intermittent Androgen Blockade in Prostate Cancer: Rationale and Clinical Experience

Cited by 20 publications

References 23 publications

Androgen via p21 Inhibits Tumor Necrosis Factor α-induced JNK Activation and Apoptosis

Androgen via p21 Inhibits Tumor Necrosis Factor α-induced JNK Activation and Apoptosis

Intermittent Androgen Castration: A Biological Reality during Intermittent Treatment in Metastatic Prostate Cancer?

Landmarks in hormonal therapy for prostate cancer

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