Exploratory study of drug plasma levels during bicalutamide 150 mg therapy co-administered with tamoxifen or anastrozole for prophylaxis of gynecomastia and breast pain in men with prostate cancer

Boccardo, Francesco; Rubagotti, Alessandra; Conti, Giario; Potenzoni, D.; Manganelli, Antonio; Monaco, Demetrio Del

doi:10.1007/s00280-005-1016-1

Cited by 15 publications

(10 citation statements)

References 10 publications

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“…As seen in Fig. 2, the assay was capable of quantitating abiraterone, enzalutamide and N-desmethyl enzalutamide in these patients with exposures in line with previous reports for abiraterone (25.3 ng/mL), enzalutamide (18.6 μg/mL), N-desmethyl enzalutamide (17.5 μg/mL), and bicalutamide (11.3 μg/mL) [19-21]. While analyzing these patient samples, we observed additional peaks in the abiraterone MRM channel (3.5 min and 8.9 min) and the N-desmethyl enzalutamide channel, see Fig.…”

Section: Resultssupporting

confidence: 88%

Simultaneous quantitation of abiraterone, enzalutamide, N -desmethyl enzalutamide, and bicalutamide in human plasma by LC–MS/MS

Kim

Parise

Holleran

et al. 2017

Journal of Pharmaceutical and Biomedical Analysis

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Inhibiting the androgen receptor (AR) pathway is an important clinical strategy in metastatic prostate cancer. Novel agents including abiraterone acetate and enzalutamide have been shown to prolong life in men with metastatic, castration-resistant prostate cancer (mCRPC). To evaluate the pharmacokinetics of AR-targeted agents, we developed and validated an LC-MS/MS assay for the quantitation of enzalutamide, N-desmethyl enzalutamide, abiraterone and bicalutamide in 0.05 mL human plasma. After protein precipitation, chromatographic separation was achieved with a Phenomenex Synergi Polar-RP column and a linear gradient of 0.1% formic acid in methanol and water. Detection with an ABI 4000Q mass spectrometer utilized electrospray ionization in positive multiple reaction monitoring mode. The assay was linear over the ranges of 1-1,000 ng/mL for abiraterone and bicalutamide and 100-30,000 ng/mL for N-desmethyl enzalutamide and enzalutamide and proved to be accurate (92.8-107.7%) and precise (largest was 15.3%CV at LLOQ for bicalutamide), and fulfilled FDA criteria for bioanalytical method validation. We demonstrated the suitability of this assay in plasma from patients who were administered enzalutamide 160 mg, abiraterone 1000 mg and bicalutamide 50 mg once a day as monotherapy or in combination. The LC-MS/MS assay that has been developed will be an essential tool that further defines the pharmacology of the combinations of androgen synthesis or AR-receptor targeted agents.

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Section: Resultssupporting

confidence: 88%

Simultaneous quantitation of abiraterone, enzalutamide, N -desmethyl enzalutamide, and bicalutamide in human plasma by LC–MS/MS

Kim

Parise

Holleran

et al. 2017

Journal of Pharmaceutical and Biomedical Analysis

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“…On the other hand, this hormonal manipulation could increase androgen secretion by blocking the negative feedback control of estrogens [14]. Although several trials have investigated the potential effects of tamoxifen co-administration on prostate-specific antigen (PSA) inhibition and on the levels of sex hormones [8,12,13,18,23-25], none of them presented long-term follow-up data. Therefore, the impact of tamoxifen therapy on outcomes, such as long-term adverse events, progression and survival, remains unclear and should be considered when prescribing this treatment.…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen for the management of breast events induced by non-steroidal antiandrogens in patients with prostate cancer: a systematic review

Kunath

Keck

Antes

et al. 2012

BMC Med

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BackgroundTamoxifen has emerged as a potential management option for gynecomastia and breast pain due to non-steroidal antiandrogens, and it is considered an alternative to surgery or radiotherapy. The objective of this systematic review was to assess the benefits and harms of tamoxifen, in comparison to other treatment options, for either the prophylaxis or treatment of breast events induced by non-steroidal antiandrogens in prostate cancer patients.MethodsWe searched CENTRAL, MEDLINE, EMBASE, reference lists, the abstracts of three major conferences and three trial registers to identify ongoing randomized controlled trials (RCTs). Two authors independently screened the articles identified, assessed the trial quality and extracted data. The protocol was prospectively registered (CRD42011001320; http://www.crd.york.ac.uk/PROSPERO).ResultsFour studies were identified. Tamoxifen significantly reduced the risk of suffering from gynecomastia (risk ratio 9RR0 0.10, 95% CI 0.05 to 0.22) or breast pain (RR 0.06, 95% CI 0.02 to 0.17) at six months compared to untreated controls. Tamoxifen also showed a significant benefit for the prevention of gynecomastia (RR 0.22, 95% CI 0.08 to 0.58) and breast pain (RR 0.25, 95% CI 0.10 to 0.64) when compared to anastrozole after a median of 12 months. One study showed a significant benefit of tamoxifen for the prevention of gynecomastia (RR 0.24, 95% CI 0.09 to 0.65) and breast pain (RR 0.20, 95% CI 0.06 to 0.65) when compared with radiotherapy at six months. Radiotherapy increased the risk of suffering from nipple erythema and skin irritation, but there were no significant differences for any other adverse events (all P > 0.05).ConclusionsThe currently available evidence suggests good efficacy of tamoxifen for the prevention and treatment of breast events induced by non-steroidal antiandrogens. The impact of tamoxifen therapy on long-term adverse events, disease progression and survival remains unclear. Further large, well-designed RCTs, including long-term follow-ups, are warranted. Also, the optimal dose needs to be clarified.

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“…110 Cyproterone acetate, a drug available outside of the United States, has anti-androgenic effects and may cause gynecomastia. 115,116 Approximately 50% of men with prostate cancer have gynecomastia, but multifactorial causes may be involved. [112][113][114] Treatment of prostate cancer with estrogens or with anti-androgens such as bicalutamide and flutamide frequently causes gynecomastia.…”

Section: Other Causesmentioning

confidence: 99%

Gynecomastia

Anawalt¹

2016

Endocrinology: Adult and Pediatric

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Exploratory study of drug plasma levels during bicalutamide 150 mg therapy co-administered with tamoxifen or anastrozole for prophylaxis of gynecomastia and breast pain in men with prostate cancer

Cited by 15 publications

References 10 publications

Simultaneous quantitation of abiraterone, enzalutamide, N -desmethyl enzalutamide, and bicalutamide in human plasma by LC–MS/MS

Simultaneous quantitation of abiraterone, enzalutamide, N -desmethyl enzalutamide, and bicalutamide in human plasma by LC–MS/MS

Tamoxifen for the management of breast events induced by non-steroidal antiandrogens in patients with prostate cancer: a systematic review

Gynecomastia

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