A Randomized Control Trial Comparing the Efficacy of Antiandrogen Monotherapy: Flutamide vs. Bicalutamide

Nakai, Yasushi; Tanaka, Nobumichi; Anai, Satoshi; Miyake, Makito; Tatsumi, Yoshihiro; Fujimoto, Kiyohide

doi:10.1007/s12672-015-0226-1

Cited by 6 publications

(6 citation statements)

References 23 publications

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“…The declines on the third day are approximately 32% (the 2-week regimen) and 34% (the 1-h regimen), while on the 7th day, it was about 72% and 66%. The decrease in PSA on day 7 was consistent with 4 weeks of bicalutamide treatment ( 21 ), indicating a strong blocking effect of apalutamide. The half-life of PSA in human serum is approximately 3 days ( 27 , 28 ).…”

Section: Discussionsupporting

confidence: 71%

“…The effect of single use of bicalutamide on endocrine in vivo has been reported: LH, FSH, testosterone and dihydrotestosterone all increased to varying degrees ( 20 ). After oral administration of flutamide and bicalutamide for 4 weeks ( 21 ), the testosterone level remained high, and the PSA level decreased by about 70%, which was comparable to that of apalutamide for 1 week ( Supplementary Table 1 ), suggesting that the time can be shortened when apalutamide is used to prevent the flare-up effect of GnRH agonist. Taking into account the half-life of PSA (about 3 days), newly generated PSA in the third day is only about 16% of the original ( Supplementary Figure 1 ), lower than administration of flutamide and bicalutamide for 4 weeks.…”

Section: Discussionmentioning

confidence: 80%

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Absence of PSA Flare With Apalutamide Administered 1 Hour in Advance With GnRH Agonists: Case Report

Liu²,

Chen³

et al. 2022

Front. Oncol.

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ObjectiveTo examine the effects of apalutamide on endocrine function and flare prevention in metastatic hormone-sensitive prostate cancer (mHSPC) patients administered GnRH agonists.MethodsThe first newly diagnosed mHSPC patient took apalutamide for 2 weeks followed by combination with GnRH agonist, as recommended by clinical guidelines. Serum luteinizing hormone (LH), testosterone, and PSA were detected during the oral administration of apalutamide before and after ADT. Eight newly diagnosed mHSPC patients innovatively took apalutamide 1 hour before GnRH agonist administration; LH, testosterone and PSA were detected before and after ADT.ResultsIn the first patient, LH and testosterone levels were increased during apalutamide monotherapy, and serum PSA levels decreased rapidly, demonstrating apalutamide effectively blocked AR signaling. In patients on the 1-hour regimen, combined treatment with apalutamide and GnRH agonists led to peak level of testosterone on day 3 and castration level on day 28, while PSA decreased continuously. No one experienced dysuria or bone pain worsen after ADT.ConclusionTaking apalutamide 1 hour in advance may effectively prevent the flare-up effect in prostate cancer patients treated with GnRH agonists. Compared with the 2-week regimen, the 1-hour regimen could simplify the treatment process and bring testosterone to castration levels in advance.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 80%

Absence of PSA Flare With Apalutamide Administered 1 Hour in Advance With GnRH Agonists: Case Report

Liu²,

Chen³

et al. 2022

Front. Oncol.

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“…In contrast to bicalutamide with no effect on adrenal androgen, flutamide was shown to significantly reduce the level of dehydroepiandrosterone (DHEA) in addition to androgen receptor blockade. [ 27 ] However, whether reduction in adrenal androgen contributes to fracture risk in patients with carcinoma of the prostate remains to be confirmed by further studies. ( Fig 2 )…”

Section: Discussionmentioning

confidence: 99%

Androgen deprivation therapy and fracture risk in Chinese patients with prostate carcinoma

et al. 2017

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ObjectiveAndrogen deprivation therapy (ADT) increases fracture risk in men with carcinoma of the prostate, but little is known about the fracture risk for different types of ADT. We studied the fracture risk amongst Chinese patients with carcinoma of the prostate prescribed different ADT regimens.Subjects and methodsThis was a single-centered observational study that involved 741 patients with carcinoma of the prostate from January 2001 to December 2011.ResultsAfter a median follow-up of 5 years, 71.7% of the study cohort received ADT and the incidence rate of fracture was 8.1%. Multivariable Cox regression analysis revealed that use of ADT was significantly associated with risk of incident fracture (Hazard Ratio [HR] 3.60; 95% Confidence Interval [95% CI] 1.41–9.23; p = 0.008), together with aged >75 years and type 2 diabetes. Compared with no ADT, all three types of ADT were independently associated with the risk of incident fracture: anti-androgen monotherapy (HR 4.47; 95% CI 1.47–13.7; p = 0.009), bilateral orchiectomy ± anti-androgens (HR 4.01; 95% CI 1.46–11.1; p = 0.007) and luteinizing hormone-releasing hormone agonists ± anti-androgens (HR 3.16; 95% CI 1.18–8.43; p = 0.022). However, there was no significant difference in the relative risks among the three types of ADT.ConclusionsFracture risk increases among all types of ADT. Clinicians should take into account the risk-benefit ratio when prescribing ADT, especially in elderly patients with type 2 diabetes.

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“…② The level of DHEA has been shown to negatively predict the response to abiraterone for patients with CRPC [ 4 ]. ③ Flutamide after bicalutamide can be effective in lowering the level of DHEA [ 5 , 6 , 8 ]. Therefore, the response to flutamide as a second-line therapy after bicalutamide can predict the response to abiraterone.…”

Section: Main Textmentioning

confidence: 99%

“…Considering the mechanism of abiraterone, Kim et al [ 4 ] reported that the level of dehydroepiandrosterone (DHEA) was a good predictor of prostate-specific antigen (PSA) response in patients with CRPC who were treated with abiraterone, and that the level of DHEA in all patients was undetectable after 8 weeks of abiraterone treatment. In our previous randomized study, which compared the levels of DHEA in castration-sensitive prostate cancer patients who were treated with flutamide versus bicalutamide monotherapy, flutamide lowered DHEA levels, but bicalutamide did not [ 5 ]. Ayub et al [ 6 ] reported that flutamide decreased the serum level of DHEA sulfate by inhibiting the activity of CYP17.…”

Section: Introductionmentioning

confidence: 99%

Response to flutamide, as second-line therapy after bicalutamide, predicts efficacy of abiraterone, not that of enzalutamide

et al. 2018

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ObjectiveThe objective of this retrospective study was to evaluate whether the effect of second-line therapy of flutamide after bicalutamide can predict the response to abiraterone.ResultsThirty-four patients received abiraterone and 32 received enzalutamide after treatment with second-line flutamide for castration-resistant prostate cancer. Prostate-specific antigen-progression-free survival during treatment with abiraterone or enzalutamide was the endpoint. The response to flutamide therapy was defined as any decrease in prostate-specific antigen compared to baseline prostate-specific antigen. Among the abiraterone-treated patients, those for whom flutamide after bicalutamide was effective showed significantly lower prostate-specific antigen changes than those for whom it was ineffective (P = 0.0175). Prostate-specific antigen-progression-free survival was significantly higher in the abiraterone patients when flutamide was effective than in the patients when it was ineffective (P = 0.027). However, in enzalutamide-treated patients, the prostate-specific antigen changes were not significantly different between those for whom flutamide after bicalutamide was effective and those for whom it was ineffective (P = 0.75). In the enzalutamide patients, prostate-specific antigen-progression-free survival was not significantly different between those for whom flutamide was effective and those for whom it was ineffective (P = 0.92). Therefore, the response to second-line flutamide predicts the efficacy of abiraterone. This information should be helpful when choosing between abiraterone and enzalutamide for patients with castration-resistant prostate cancer.

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A Randomized Control Trial Comparing the Efficacy of Antiandrogen Monotherapy: Flutamide vs. Bicalutamide

Cited by 6 publications

References 23 publications

Absence of PSA Flare With Apalutamide Administered 1 Hour in Advance With GnRH Agonists: Case Report

Absence of PSA Flare With Apalutamide Administered 1 Hour in Advance With GnRH Agonists: Case Report

Androgen deprivation therapy and fracture risk in Chinese patients with prostate carcinoma

Response to flutamide, as second-line therapy after bicalutamide, predicts efficacy of abiraterone, not that of enzalutamide

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