Monoterapie antyandrogenowe

Monoterapie antyandrogenowe

Nieprzeczytany postautor: zosia bluszcz » 23 lut 2018, 08:02


Comparison of bicalutamide with other antiandrogens


Contents

1 Overview
2 First-generation NSAAs
2.1 Effectiveness
2.2 Tolerability and safety
3 Second-generation NSAAs
3.1 Effectiveness
3.2 Tolerability and safety
4 Steroidal antiandrogens
4.1 Effectiveness
4.2 Tolerability and safety
5 Castration and GnRH analogues
5.1 Effectiveness
5.2 Tolerability and safety
6 References

Overview
Bicalutamide and the other nonsteroidal antiandrogens (NSAAs), since their introduction, have largely replaced cyproterone acetate (CPA), an older drug and steroidal antiandrogen (SAA), in the treatment of prostate cancer.[1][2][3][4] Bicalutamide was the third NSAA to be marketed, with flutamide and nilutamide preceding, and followed by enzalutamide.[5][6] Relative to the earlier antiandrogens, bicalutamide has substantially reduced toxicity, and in contrast to them, is said to have an excellent and favorable safety profile.[4][7][8][9] For these reasons, as well as superior potency, tolerability, and pharmacokinetics, bicalutamide is preferred and has largely replaced flutamide and nilutamide in clinical practice.[10][11][12] In accordance, bicalutamide is the most widely used antiandrogen in the treatment of prostate cancer.[13][14][15] Between January 2007 and December 2009, it accounted in the U.S. for about 87.2% of NSAA prescriptions.[16] Prior to the 2012 approval of enzalutamide, a newer and improved NSAA with greater potency and efficacy,[7] bicalutamide was regarded as the standard-of-care antiandrogen in the treatment of the prostate cancer.[6][7][17]

https://en.wikipedia.org/wiki/Compariso ... iandrogens
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Re: Monoterapie antyandrogenowe

Nieprzeczytany postautor: zosia bluszcz » 23 lut 2018, 08:09


Monoterapia Enzalutamidem


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Re: Monoterapie antyandrogenowe

Nieprzeczytany postautor: zosia bluszcz » 23 lut 2018, 08:14

Bicalutamide monotherapy preserves bone mineral density, muscle strength and has significant health-related quality of life benefits for osteoporotic men with prostate cancer (2010)

Abstract
Study Type – Therapy (case series)

Level of Evidence 4

What's known on the subject? and What does the study add?

LH-RH agonists, by suppressing testosterone and oestrogen, cause rapid bone demineralization and reduce both muscle strength and health related quality of life (HRQOL) in prostate cancer. A significant proportion of patients about to commence ADT are already osteoporotic, placing them at fracture risk. Bicalutamide monotherapy elevates testosterone and oestrogen levels, is licensed in locally advanced disease, but significantly underutilised in this setting.

Whereas previous studies have assessed BMD and HRQOL in men across a range of BMDs, this study specifically evaluated osteoporotic men who are often older, with reduced muscle strength and with potentially the most to gain from bicalutamide monotherapy. BMD, muscle strength and HRQOL were each maintained across a 12-month period, suggesting that this treatment option should be considered more often by physicians and patients counseled appropriately.

OBJECTIVES
• To evaluate changes in bone mineral density (BMD), body composition, muscle strength and health-related quality of life (HRQL) during bicalutamide (150 mg) monotherapy in osteoporotic patients with non-metastatic locally advanced prostate cancer. Osteoporosis is prevalent in men presenting with prostate cancer and also a common side effect of treatment with luteinizing hormone-releasing hormone agonists, which are associated with decreased BMD and loss of lean body mass and suppress testosterone, unlike bicalutamide, which results in an increase in serum testosterone and oestrogen levels.

PATIENTS AND METHODS
• Forty-two men with non-metastatic locally advanced prostate cancer and osteoporosis (T-score ≤−2.5) were treated with bicalutamide (150 mg) monotherapy. BMD was measured at baseline and 1 year. HRQL was assessed 3-monthly using the RAND 36-Item Health Survey and University of California Los Angeles Prostate Cancer Index questionnaires. Bone turnover markers, liver function tests, prostate-specific antigen, testosterone, oestradiol and haemoglobin were measured at baseline, at 3 weeks and 3-monthly thereafter. Arm anthropometry and dynamometry assessed fat mass, skeletal muscle mass and quadriceps strength.

RESULTS
• BMD was maintained (+2.1% lumbar spine, +1.2% total hip and +1.1% forearm). Prostate-specific antigen decreased by 88% at 3 months. Testosterone and oestradiol had increased at 1 year by 58% and 42%, respectively. No increase in bone turnover markers was seen over 1 year. Quadriceps muscle strength was maintained. General and prostate cancer-specific HRQL were maintained throughout the study, with no significant reductions in physical or sexual function. Adverse events included breast pain and gynaecomastia.

CONCLUSIONS
• Bicalutamide preserves BMD, muscle strength and HRQL in osteoporotic men with non-metastatic locally advanced prostate cancer. It provides an alternative to medical castration for well informed men at high fracture risk and those wishing to retain physical and sexual activity, with luteinizing hormone-releasing hormone agonists being reserved for those failing to respond or relapsing.


http://onlinelibrary.wiley.com/doi/10.1 ... 726.x/full
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Re: Monoterapie antyandrogenowe

Nieprzeczytany postautor: bela71 » 23 lut 2018, 19:36

Interesujący artykuł z 2015 roku analizujący zasadność kontynuowania deprywacji androgenowej po osiągnięciu hormonooporności.



Do we need to continue androgen deprivation therapy?
21 March 2015 Prof. Dr. Axel Merseburger

The European Association of Urology (EAU) guideline clearly states that patients with metastatic castrateresistant prostate cancer (mCRPC) should indefinitely continue androgen deprivation therapy (ADT); this recommendation applies to metastatic CRPC (mCRPC) and non-metastatic CRPC (nmCRPC)1. Other guidelines, such as that from the American Urological Association (AUA)2 and the National Comprehensive Cancer Network (NCCN)3, likewise mention the need to maintain ADT when mCRPC develops.

As support, all randomised controlled trials of the many newer agents for mCRPC, including abiraterone, enzalutamide, sipuleucel-T, radium 223 and cabazitaxel4-10 all had continuation of ADT and mainstay of castration levels of testosterone (<50 ng/ dl) as an inclusion criterion. However, this does not prove the value of ADT in this setting. In metastatic disease, while hormonal treatment improves symptoms11, there is no conclusive prospective evidence that lowering testosterone levels improves life expectancy12. With the event of evaluating novel substances in the setting of non-metastatic CRPC, the value of combining ADT with tertiary hormonal manipulation (e.g. Enzalutamide, Abiraterone, ARN-509, etc.) has not been investigated.

Sparse evidence


The evidence for continuing ADT in metastatic prostate cancer is based on sparse literature. A single study demonstrated that androgen priming in a small group of patients (n=85) using chemotherapy regimens that are now outdated altered the prognosis13.

However, it is becoming clear that within the prostate and prostate tumour microenvironment androgen activity continues even when serum testosterone levels are suppressed by ADT14, and intracrine androgen synthesis is sufficient to activate androgen receptor target genes15. Adaptive alterations include alternative androgen synthesis pathways, and androgen receptor overexpression, mutation and splice variations16. Furthermore, many mechanisms that may confer castration-resistance still require, or are enhanced by, the presence of androgens or androgen receptor ligands. Together these observations suggest that treatment combinations that include ADT and suppress intracrine and systemic androgen contributions are required in CRPC.

The presentation will cover the evidence and rationale for continuing ADT in CRPC when other treatments are initiated, and aim to provide clear statements on this issue.



[Artykuł w dalszej części omawia uzasadnienia podawane dla kontynuacji ADT przy aleczeniu abirateronem, enzalutamidem i chemioterapią. Ważne są odniesienia do badań klinicznych.]

http://uroweb.org/do-we-need-to-continu ... n-therapy/
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Re: Monoterapie antyandrogenowe

Nieprzeczytany postautor: bela71 » 23 lut 2018, 20:06

Jedyne chyba jak dotąd badania na temat monoterapii enzalutamidem:

Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results
http://www.europeanurology.com/article/S0302-2838(15)00070-6/fulltext


I, sądząc po nazwiskach badaczy, sprawozdanie z dłuższej obserwacji tego samego badania (abstrakt):

Long-Term Antitumor Activity and Safety of Enzalutamide Monotherapy in Hormone Naïve Prostate Cancer: 3-Year Open Label Followup Results.

https://www.ncbi.nlm.nih.gov/pubmed/28867562
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