Serum testosterone levels and testosterone ‘bounce’ phenomenon predict response to novel anti-androgen therapies in castration-resistant prostate cancer

2021 ◽  
Author(s):  
Yu Guang Tan ◽  
Sheriff Z.H. Quek ◽  
Hong Hong Huang ◽  
Henry S.S. Ho ◽  
John S.P. Yuen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Serum Testosterone ◽  
Castration Resistant Prostate Cancer ◽  
Testosterone Levels ◽  
Castration Resistant

Serum testosterone level and overall survival in first-line abiraterone and enzalutamide for metastatic castration-resistant prostate cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17545-e17545
Author(s):  
Maysa Tamara Silveira Vilbert ◽  
Marcelle Goldner Cesca ◽  
Natasha Carvalho Pandolfi ◽  
Vinicius Fernando Calsavara ◽  
Bruno Cezar de Mendonça Uchôa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Testosterone Level ◽  
Serum Testosterone ◽  
Serum Testosterone Level ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Testosterone Levels ◽  
Castration Resistant ◽  
Low Serum

e17545 Background: Androgen receptor-targeted agents Abiraterone and Enzalutamide (Abi/Ez) prolonged overall survival in metastatic castration resistant prostate cancer (mCRPC). Patients with very-low serum testosterone levels seem to have less benefit from these therapies as well as more aggressive prostate cancer. Methods: A retrospective observational cohort study was conducted to evaluate whether a serum testosterone measured at time of start first-line therapy with Abi/Ez is related to overall survival (OS) and time-to-treatment failure (TTF) in mCRPC patients. Kaplan-Meier survival estimates and Cox-regression models were used for time-to-event analyses. The best cut-off for testosterone was defined using Log-rank statistics (Lausen and Schumacher). X² test and Mann-Whitney U-test were applied to compare categorical and continuous variables, respectively. Logistic regression was used to assess characteristics related to serum testosterone levels. Statistical significance was fixed at 0.05. Results: From May 2012 to February 2017, 100 patients were assessed. Median follow-up was 27.8 months (range 2.23 to 68.26). Pts with a high testosterone level ( > 28.2; n = 20) achieved a significantly higher OS (median 66.0 vs 31.9 mo, testosterone > 28.2 HR: 0.206, 95% CI 0.074 to 0.571, p = 0.002) and TTF (median 30.6 vs 11.8 mo, testosterone > 28.2 HR: 0.408, 95%CI 0.219 to 0.762, p = 0.005) than pts with a low serum testosterone level ( < 28.2; n = 80), regardless of receiving therapy with either Abi (n = 69) or Ez (n = 31). Pts with a higher testosterone level were younger (median 67.7 vs 73.6 years; p = 0.026), had a higher body mass index (BMI) (28.5 vs 25.9, p = 0.023) and a lower PSA at start Abi/Ez (12 vs 26, p = 0.031) than pts with lower values. Age (OR 0.93, 95%CI 0.8 to 0.9, p = 0.021), BMI (OR 1.21, 95%CI 1.1 to 1.4, p = 0.006) and baseline PSA (OR 1.2, 95%CI 1.03 to 1.4, p = 0.020) were significantly associated with testosterone > 28.2. After 4 months of Abi/Ez treatment, PSA decrease > 50% of baseline was seen more frequently in high testosterone levels group than in low testosterone levels pts (90% vs 57.5% of pts, respectively, p = 0.007). Conclusions: Pts with high levels of testosterone ( > 28.2) achieved a better OS and TTF when treated with Abi/Ez in first-line mCRPC than those with low levels. Testosterone can be considered a prognostic and predictive biomarker in this scenario, and could be used in treatment decision for this population.

Higher serum testosterone levels predict poor prognosis in castration‐resistant prostate cancer patients treated with docetaxel

The Prostate ◽  
2019 ◽  
Vol 80 (3) ◽  
pp. 247-255 ◽  
Author(s):  
Keisuke Ando ◽  
Shinichi Sakamoto ◽  
Nobushige Takeshita ◽  
Ayumi Fujimoto ◽  
Maihulan Maimaiti ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Serum Testosterone ◽  
Castration Resistant Prostate Cancer ◽  
Testosterone Levels ◽  
Castration Resistant

Testosterone levels and androgen receptor copy number variations in castration‐resistant prostate cancer treated with abiraterone or enzalutamide

The Prostate ◽  
2019 ◽  
Vol 79 (11) ◽  
pp. 1211-1220 ◽  
Author(s):  
Cristian Lolli ◽  
Delia Lisi ◽  
Vincenza Conteduca ◽  
Giorgia Gurioli ◽  
Emanuela Scarpi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Copy Number ◽  
Copy Number Variations ◽  
Castration Resistant Prostate Cancer ◽  
Testosterone Levels ◽  
Castration Resistant

Abiraterone acetate plus prednisone (AA+P) without continuing LHRH-therapy in patients with metastatic chemotherapy: Naive castrations-resistant prostate cancer—Results from the SPARE-trial (NCT02077634).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5046-5046 ◽  
Author(s):  
Carsten Henning Ohlmann ◽  
Christoph Ruessel ◽  
Roger Zillmann ◽  
Eva Hellmis ◽  
Henrik Suttmann ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Objective Response ◽  
Serum Testosterone ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Testosterone Levels ◽  
Psa Response ◽  
Secondary Endpoints ◽  
Psa Progression ◽  
Lhrh Therapy

5046 Background: The value of continuation of androgen deprivation therapy (ADT) in metastatic castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase/C17,20 lyase (Cyp17)-inhibitor, abiraterone acetate (AA), which in combination with prednisone (P), has the ability to further suppress serum testosterone levels over ADT alone, continuation of ADT seems to be negligible. Methods: The exploratory phase II trial randomized CRPC patients to receive continued ADT plus AA+P versus AA+P alone (NCT02077634), funded by Jansen-Cilag GmbH, Germany. The primary endpoint was rate of rPFS at month 12, not powered for a direct comparison between treatment arms. Secondary endpoints included PSA response rate, objective response, time to PSA progression and safety. Results: Altogether, 67 patients were randomized between 08/2014 to 04/2017. Median testosterone-levels (T) remained far below castrate-levels throughout treatment in all patients. However, in 6 patients (18%) from Arm B, T-levels increased above castrate levels within 28 days after cessation of AA+P treatment. Median treatment duration is shorter in Arm A. Safety analysis is underway and results will be presented. Conclusions: Results of this exploratory study suggest that treatment with AA+P without ADT may be effective in patients with mCRPC and that ADT may not be necessary in patients receiving AA+P. In some patients, serum-testosterone levels may rise rapidly upon treatment discontinuation so that the levels should be monitored closely. Clinical trial information: NCT02077634. [Table: see text]

Androgen receptor independent acquired mechanisms of resistance to enzalutamide in castration-resistant prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 129-129
Author(s):  
Russell Zelig Szmulewitz ◽  
Steve Kregel ◽  
Masis Isikbay ◽  
Yi Cai ◽  
James Lin Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cell Lines ◽  
Dna Sequences ◽  
Castration Resistant Prostate Cancer ◽  
Testosterone Levels ◽  
Castration Resistant ◽  
Stat Signaling

129 Background: Enzalutamide (MDV3100) is a second generation androgen receptor (AR) antagonist with potent activity in the treatment of castration resistant prostate cancer (CRPC). However, most patients develop resistance and progression of disease; thus there is a critical need to identify novel targetable pathways mechanistically linked to this resistance. Methods: A panel of four prostate cancer cell lines (LAPC-4, LNCaP, VCaP, and CWRR1) was created each with a different AR status that are resistant to MDV3100 by culturing cells long-term less than 6 months in the drug at pharmacologic levels. The MDV3100 resistant (MDV-R) lines were assayed for proliferation, viability, resistance to docetaxel, and tumor take of subcutaneous xenografts. AR expression and ligand binding domain (LBD) DNA sequences were analyzed. Gene expression microarray comparison of resistant and non-resistant parental cell lines was performed. Prostate-specific antigen (PSA) and testosterone levels were analyzed from conditioned media. Results: Cell lines demonstrated heterogeneous growth characteristics.In vivo studies depicted increased or unaltered tumor take and growth in castrate athymic mice. In some cell lines growth was increased in vitro when drug was withdrawn; yet this growth was inhibited by physiological testosterone levels, both in vitro and in vivo. MDV-R cells remained sensitive to docetaxel in vitro and had increased levels of ARmRNA. However, total AR protein levels were lower or unchanged than the parental lines, with evidence for increased truncated forms of AR. The AR LBD acquired no new mutations. Secreted PSA was lower in all but one MDV-R line. Gene expression analyses demonstrated strong upregulation of IGFBP3 in all MDV-R cells. Pathway analysis implicated increased IGF and JAK/STAT signaling whereas mammalian target of rapamycin (mTOR) signaling was decreased. Conclusions: Although AR-mediated pathways contribute to enzalutamide resistance, a broader approach across several cell lines suggests that there may be even a greater contribution from pleiotropic, non-AR mediated mechanisms. Such mechanisms may include IGF signaling, JAK/STAT signaling and modulation of mTOR.

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