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Partial response of liver metastases treated with abiraterone in castration-resistant prostate cancer: A case report.

ABSTRACT: Docetaxel is the current first-line treatment for castration-resistant prostate cancer (CRPC), following failure to respond to maximal androgen blockade (MAB). Patients who fail to respond to docetaxel may receive cabazitaxel or abiraterone; however, there are no recommendations on which of these two agents should be used first. Here, we present a case of a male patient suffering from CRPC with liver and lymph node metastases, in which abiraterone achieved a partial response, according to RECIST criteria. In the literature, visceral involvement in patients with advanced prostate cancer is an infrequent occurrence; it affects 18-22% of patients. In the pivotal study concerning docetaxel-resistant patients, abiraterone was compared with a placebo and the forest plot for survival demonstrated that patients with visceral involvement have significantly benefited from abiraterone. In the TROPIC trial comparing cabazitaxel with mitoxantrone, the proportion of patients with visceral disease was ?25% in both arms and there was no difference in overall survival in this subgroup of patients. In our case, we observed a significant activity of abiraterone in lymph node and liver metastases. If confirmed in large studies, this observation may raise concerns over whether to treat patients suffering from CRPC and visceral metasis with chemotherapy or hormone therapy.

SUBMITTER: Marech I

PROVIDER: S-EPMC3701088 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Partial response of liver metastases treated with abiraterone in castration-resistant prostate cancer: A case report.

Marech Ilaria I Vacca Angelo A Sivestris Nicola N Gnoni Antonio A Lorusso Vito V

Oncology letters 20130329 6

Docetaxel is the current first-line treatment for castration-resistant prostate cancer (CRPC), following failure to respond to maximal androgen blockade (MAB). Patients who fail to respond to docetaxel may receive cabazitaxel or abiraterone; however, there are no recommendations on which of these two agents should be used first. Here, we present a case of a male patient suffering from CRPC with liver and lymph node metastases, in which abiraterone achieved a partial response, according to RECIST ...[more]

PMID: 23833660

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Project description:BackgroundLoss of the tumor suppressor phosphatase and tensin homolog (PTEN) occurs frequently in prostate cancers. Preclinical evidence suggests that activation of PI3K/AKT signaling through loss of PTEN can result in resistance to hormonal treatment in prostate cancer.ObjectiveTo explore the antitumor activity of abiraterone acetate (abiraterone) in castration-resistant prostate cancer (CRPC) patients with and without loss of PTEN protein expression.Design, setting, and participantsWe retrospectively identified patients who had received abiraterone and had hormone-sensitive prostate cancer (HSPC) and/or CRPC tissue available for PTEN immunohistochemical analysis.Outcome measurements and statistical analysisThe primary end point was overall survival from initiation of abiraterone treatment. Relationship with outcome was analyzed using multivariate Cox regression and log-rank analyses.Results and limitationsA total of 144 patients were identified who had received abiraterone post-docetaxel and had available tumor tissue. Overall, loss of PTEN expression was observed in 40% of patients. Matched HSPC and CRPC tumor biopsies were available for 41 patients. PTEN status in CRPC correlated with HSPC in 86% of cases. Loss of PTEN expression was associated with shorter median overall survival (14 vs 21 mo; hazard ratio [HR]: 1.75; 95% confidence interval [CI], 1.19-2.55; p=0.004) and shorter median duration of abiraterone treatment (24 vs 28 wk; HR: 1.6; 95% CI, 1.12-2.28; p=0.009). PTEN protein loss, high lactate dehydrogenase, and the presence of visceral metastases were identified as independent prognostic factors in multivariate analysis.ConclusionsOur results indicate that loss of PTEN expression was associated with worse survival and shorter time on abiraterone treatment. Further studies in larger and prospective cohorts are warranted.Patient summaryPTEN is a protein often lost in prostate cancer cells. In this study we evaluated if prostate cancers that lack this protein respond differently to treatment with abiraterone acetate. We demonstrated that the survival of patients with loss of PTEN is shorter than patients with normal PTEN expression.

Project description:PurposeMetastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition.MethodsMAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort.ResultsMedian rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events.ConclusionCombination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.[Media: see text].

Project description:Androgen deprivation therapy remains the single most effective treatment for the initial therapy of advanced prostate cancer, but is uniformly marked by progression to castration-resistant prostate cancer (CRPC). Residual tumor androgens and androgen axis activation are now recognized to play a prominent role in mediating CRPC progression. Despite suppression of circulating testosterone to castrate levels, castration does not eliminate androgens from the prostate tumor microenvironment and residual androgen levels are well within the range capable of activating the androgen receptor (AR) and AR-mediated gene expression. Accordingly, therapeutic strategies that more effectively target production of intratumoral androgens are necessary. The introduction of abiraterone, a potent suppressor of cytochrome P450 17 α-hydroxysteroid dehydrogenase-mediated androgen production, has heralded a new era in the hormonal treatment of men with metastatic CRPC. Herein, the androgen and AR-mediated mechanisms that contribute to CRPC progression and establish cytochrome P450 17 α-hydroxysteroid dehydrogenase as a critical therapeutic target are briefly reviewed. The mechanism of action and pharmacokinetics of abiraterone are reviewed and its recently described activity against AR and 3-β-hydroxysteroid dehydrogenase is discussed. The Phase I and II data initially demonstrating the efficacy of abiraterone and Phase III data supporting its approval for patients with metastatic CRPC are reviewed. The safety and tolerability of abiraterone, including the incidence and management of side effects and potential drug interactions, are discussed. The current place of abiraterone in CRPC therapy is reviewed and early evidence regarding cross-resistance of abiraterone with taxane therapy, mechanisms of resistance to abiraterone, and observations of an abiraterone withdrawal response are presented. Future directions in the use of abiraterone, including optimal dosing strategies, the role of abiraterone in earlier disease settings, including castration sensitive, biochemically recurrent, or localized disease, and the rationale for combinatorial treatment strategies of abiraterone with enzalutamide and other targeted agents are also discussed.

Project description:Abiraterone acetate (AA), a CYP17 inhibitor, now has a crucial role in the treatment of castration-resistant prostate cancer (CRPC), and previous studies have reported several prognostic clinical factors for AA treatment. The neutrophil-to-lymphocyte ratio (NLR) has also been investigated for a CRPC treatments in a few reports, however it has not been identified to be a prognostic factor for AA treatment in Japanese patients. The present study aimed to assess the association of the baseline NLR with the overall survival (OS) in CPRC patients treated by AA. The present study retrospectively reviewed a total of 90 consecutive patients with CRPC treated with AA from 2011 to 2016 at Yokohama City University Medical Center and National Cancer Center Hospital East. The primary endpoint of the study was the OS, which was defined as the survival from the start of AA administration. The secondary endpoint was the prostate-specific antigen (PSA) response. PSA response was defined as a reduction in antigen levels of >50%. Complete blood cell counts were performed, and the NLR was calculated using the neutrophil and lymphocyte counts obtained on the same day or a few days prior to the initiation of AA therapy. The NLR cut-off point was determined to be 3.76 for the OS, and divided into the high NLR group of 34 patients and the low NLR group of 56 patients. A PSA response was obtained in 8 patients (23.5%) in the high NLR group and in 24 (42.9%) in the low NLR group. The difference of PSA response between the two groups was significant (P=0.037). Kaplan-Meier curves demonstrated that a high NLR [NLR ?3.76; median OS: 8.4 months; 95% confidence interval (CI): 6.325-10.475 months] was correlated with a risk of mortality compared with a low NLR (NLR <3.76; median OS not reached). A multivariate analysis demonstrated that the NLR was an independent predictor for the OS (hazard ratio: 2.682; 95% CI: 1.143-6.293; P=0.023). The findings suggest that the NLR may be a useful novel biomarker for predicting the prognosis of CRPC patients treated with AA.

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Partial response of liver metastases treated with abiraterone in castration-resistant prostate cancer: A case report.

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Partial response of liver metastases treated with abiraterone in castration-resistant prostate cancer: A case report.

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