Potential Benefits of Intermittent Androgen Suppression Therapy in the Treatment of Prostate Cancer: A Systematic Review of the Literature

Abrahamsson, Per‐Anders

doi:10.1016/j.eururo.2009.07.049

Cited by 175 publications

(144 citation statements)

References 57 publications

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“…The status of further phase-II and ongoing phase-III trials of IAS is the subject of several review articles (Gleave 1998;Rashid & Chaudhary 2004;Bhandari et al 2005;Abrahamsson 2010). Figure 1 is a schematic illustration showing a continuation of cycles of on-and off-treatment periods under IAS with the serum PSA levels oscillating in a clinically feasible range.…”

Section: Introductionmentioning

confidence: 99%

Mathematical modelling of prostate cancer growth and its application to hormone therapy

Tanaka

Hirata

Goldenberg³

et al. 2010

Phil. Trans. R. Soc. A.

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Hormone therapy in the form of androgen deprivation is a major treatment for advanced prostate cancer. However, if such therapy is overly prolonged, tumour cells may become resistant to this treatment and result in recurrent fatal disease. Long-term hormone deprivation also is associated with side effects poorly tolerated by patients. In contrast, intermittent hormone therapy with alternating on-and off-treatment periods is a possible clinical strategy to delay progression to hormone-refractory disease with the advantage of reduced side effects during the off-treatment periods. In this paper, we first overview previous studies on mathematical modelling of prostate tumour growth under intermittent hormone therapy. The model is categorized into a hybrid dynamical system because switching between on-treatment and off-treatment intervals is treated in addition to continuous dynamics of tumour growth. Next, we present an extended model of stochastic differential equations and examine how well the model is able to capture the characteristics of authentic serum prostate-specific antigen (PSA) data. We also highlight recent advances in time-series analysis and prediction of changes in serum PSA concentrations. Finally, we discuss practical issues to be considered towards establishment of mathematical model-based tailor-made medicine, which defines how to realize personalized hormone therapy for individual patients based on monitored serum PSA levels.

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Section: Introductionmentioning

confidence: 99%

Mathematical modelling of prostate cancer growth and its application to hormone therapy

Tanaka

Hirata

Goldenberg³

et al. 2010

Phil. Trans. R. Soc. A.

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“…After testosterone recovered to normal level, the side effects of ADT would disappear completely. 13,14 Time of testosterone recovery to supracastrate level after ADT has been investigated in previous studies. In a randomized clinical trial using intermittent hormonal therapy for PCa patients with increasing PSA after definitive local treatment, Gulley et al 6 found that after 6 months of ADT, more than 90% patients achieved supracastrate serum testosterone level by 18 weeks.…”

Section: Discussionmentioning

confidence: 99%

Kinetics of testosterone recovery in clinically localized prostate cancer patients treated with radical prostatectomy and subsequent short-term adjuvant androgen deprivation therapy

Dai¹,

Qu²,

Kong³

et al. 2013

Asian J Androl

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Androgen deprivation therapy (ADT) is a standard treatment for metastatic, recurrent and locally advanced prostate cancer (PCa). The aim of this study is to investigate the timing and extent of testosterone recovery in clinically localized PCa patients treated with radical prostatectomy (RP) and subsequent short-term adjuvant ADT. A total of 95 localized PCa patients underwent RP and 9-month adjuvant ADT were included in this prospective study. Serum testosterone level was measured before adjuvant ADT, at ADT cessation, and at 1, 3, 6, 9 and 12 months after cessation of ADT. A Cox proportional hazards model was used to assess variables associated with the time of testosterone normalization. The results showed that median patient age was 67 years and median testosterone level before adjuvant ADT was 361 (230-905) ng dl 21 . All patients finished 9-month adjuvant ADT and achieved castrate testosterone level. At 3 months after ADT cessation, testosterone recovered to supracastrate level in 97.9% patients and to normal level in 36.9% patients. The percentage of patients who recovered to normal testosterone level increased to 66.3%, 86.3% and 92.6% at 6, 9 and 12 months, respectively. Cox regression model found that higher baseline testosterone level (o300 ng dl 21 ) was the only variable associated with a shorter time to testosterone normalization (hazard ratio: 1.98; P 5 0.012). In conclusion, in most patients, testosterone recovered to supracastrate level at 3 months and to normal level at 12 months after 9-month adjuvant ADT cessation. Patients with higher baseline testosterone level need shorter time of testosterone normalization.

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“…The guidelines of the Chinese Urological Association use a single threshold for stopping or resuming ADT 9 in all prostate cancers, but the majority of literatures, including those proposed by the European Association of Urology guidelines, 10 adopted a higher threshold in advanced or metastatic disease than in relapsing disease after radical therapy for prostate cancer. [11][12][13] At present, there is no consensus with regard to the optimal threshold. The most commonly used PSA value for the withdrawal of ADT is less than 4 ng ml 21 , and the most widely used PSA value for the resumption of ADT is more than 10 or 20 ng ml 21 .…”

Section: Discussionmentioning

confidence: 99%

“…The most commonly used PSA value for the withdrawal of ADT is less than 4 ng ml 21 , and the most widely used PSA value for the resumption of ADT is more than 10 or 20 ng ml 21 . [11][12][13] Most patients with advanced PCa were able to achieve temporary palliation at the beginning of HT, and intermittent maximal androgen blockade may help delay progression to androgen independence; unfortunately, however, nearly all hormone-sensitive PCa patients ultimately develop hormone-refractory PCa within a median of 18-24 months. 2 At present, there are no effective treatment options, and most patients have a very poor prognosis with a subsequent median survival time of no more than 2 years.…”

Section: Discussionmentioning

confidence: 99%

The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy

Wu¹,

Wang²,

Xu³

et al. 2011

Asian J Androl

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The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound (HIFU) combined with (1) low-dose external beam radiotherapy (LRT) as supplemental therapy for advanced prostate cancer (PCa) following hormonal therapy (HT). Our definition of HIFU1LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam radiotherapy (CRT). We performed a prospective, controlled and non-randomized study on 120 patients with advanced PCa after HT who received HIFU, CRT, HIFU1LRT and HT alone, respectively. CT/MR imaging showed the primary tumours and pelvic lymph node metastases visibly shrank or even disappeared after HIFU1LRT treatment. There were significant differences among four groups with regard to overall survival (OS) and disease-specific survival (DSS) curves (P50.018 and 0.015). Further comparison between each pair of groups suggested that the long-term DSS of the HIFU1LRT group was higher than those of the other three groups, but there was no significant difference between the HIFU1LRT group and the CRT group. Multivariable Cox's proportional hazard model showed that both HIFU1LRT and CRT were independently associated with DSS (P50.001 and 0.035) and had protective effects with regard to the risk of death. Compared with CRT, HIFU1LRT significantly decreased incidences of radiation-related late gastrointestinal (GI) and genitourinary (GU) toxicity grade oII. In conclusion, long-term survival of patients with advanced PCa benefited from strengthening local control of primary tumour and regional lymph node metastases after HT. As an alternative to CRT, HIFU1LRT showed good efficacy and better safety.

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Potential Benefits of Intermittent Androgen Suppression Therapy in the Treatment of Prostate Cancer: A Systematic Review of the Literature

Cited by 175 publications

References 57 publications

Mathematical modelling of prostate cancer growth and its application to hormone therapy

Mathematical modelling of prostate cancer growth and its application to hormone therapy

Kinetics of testosterone recovery in clinically localized prostate cancer patients treated with radical prostatectomy and subsequent short-term adjuvant androgen deprivation therapy

The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy

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