scholarly journals Chromogranin A predicts outcome in prostate cancer patients treated with abiraterone

2014 ◽  
Vol 21 (3) ◽  
pp. 487-493 ◽  
Author(s):  
Salvatore Luca Burgio ◽  
Vincenza Conteduca ◽  
Cecilia Menna ◽  
Elisa Carretta ◽  
Lorena Rossi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromogranin A ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Psa Response ◽  
Group A ◽  
Group 3 ◽  
Group B

In this retrospective study, we evaluated the chromogranin A (CgA) baseline value as a predictor of clinical outcome in patients with metastatic castration-resistant prostate cancer (CRPC) treated with abiraterone 1000 mg per day, whose disease progressed after docetaxel chemotherapy. In the 48 evaluable patients, serum CgA level was normal when <120 ng/ml (group A, n=16), within three times the upper normal value (UNV) when between 120 and 360 (group B, n=16), more than three times the UNV when ≥360 ng/ml (group C, n=16). Decline in PSA level ≥50% or more (PSA RR) was observed in 26 of 48 (54%) patients. PSA response rate did not correlate with the CgA groups. CgA levels more than three times the UNV predicted an early radiological progressive disease in eight of 11 cases (73%). The median progression-free survival (PFS) among the CgA groups A, B, and C was 9.2, 9.2, and 4.8 months respectively, P=0.0459. The median overall survival (OS) among the CgA groups was 19.0, 18.8, and 10.8 months respectively, P=0.2092. In the multivariate analysis, PSA RR (nonresponsive vs responsive) and CgA levels (group 3 vs groups 1+2) were predictors of PFS (P=0.0002 and P=0.0047 respectively), whereas PSA RR only was significantly associated with OS (P=0.0024), while CgA levels remained of borderline significance (P=0.0919). A serum CGA level more than three times the UNV predicted PFS and showed a trend vs OS prediction, independently from PSA response, in CRPC patients treated with abiraterone.

Analysis of prognostic biomarkers of response in patients with metastatic castration-resistant prostate cancer treated with abiraterone: A. C. Camargo Cancer Center experience.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 335-335
Author(s):  
Pedro Henrique Ferraro Silveira ◽  
Marcelo Corassa ◽  
Aldo Lourenço Abbade Dettino ◽  
José Augusto Rinck ◽  
Thiago Bueno Oliveira ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Prognostic Biomarkers ◽  
Cancer Center ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Clinical Biomarkers ◽  
Psa Response ◽  
Clinical Records

335 Background: Despite therapeutic progress in the management of advanced prostate cancer during the past decade, metastatic castration-resistant prostate cancer (mCRPC) remains a disease that causes substantial morbidity and mortality worldwide. A greater understanding of biomarkers permits to guide personalized therapy and can inform clinical trials tailored to men most likely to derive benefit from a given therapy. We aimed to identify prognostic biomarker candidates of Abiraterone Acetate (AA) response in mCRPC patients. Methods: A retrospective clinical records analysis of mCRPC patients treated with AA at A. C. Camargo Cancer Center between January 2012 to December 2016 was realized. Baseline clinical parameters evaluated were: Age, ECOG performance status, metastatic disease at diagnosis, Gleason score, prostate-specific antigen (PSA), Neuroendocrine differentiation, duration of previous androgen-deprivation therapy (ADT), PSA doubling-time (PSAdt), Timing of AA (chemotherapy-naïve or not), PSA response and alkaline phosphatase (ALP) level. Data were analyzed in relation to progression free survival (PFS) stratified by each parameter. Results: We included 141 patients with mCRPC treated with AA to correlate prognostic biomarkers with PFS. Five risk factors individually were associated with poor prognosis and a high risk to progression during AA therapy and were included in the final model: ECOG ≥2 [Relative risk (RR) = 1.52]; PSAdt < 3 months (RR = 2.7); PSA response ( < 50% decline) (RR = 3.03); AA post docetaxel (RR = 1.63) and duration of previous ADT < 12 months (RR = 1.52). The probability to progression free survival in patients receiving AA calculated in 1, 2 and 3 years, was 39,2%, 15,2% and 6,2%, respectively. Conclusions: This analysis identified five factors used to model survival in mCRPC patients treat with AA in our institutional series. Whereas no biomarker has been validated as a predictor of response to a therapy in mCRPC, these those potential clinical biomarkers may help clinicians in distinguishing patients with mCRPC who would obtain the best survival benefit from AA treatment.

scholarly journals Comparison of Radiographic Progression-Free Survival and PSA Response on Sequential Treatment Using Abiraterone and Enzalutamide for Newly Diagnosed Castration-Resistant Prostate Cancer: A Propensity Score Matched Analysis from Multicenter Cohort

2019 ◽  
Vol 8 (8) ◽  
pp. 1251 ◽  
Author(s):  
Kazumasa Komura ◽  
Yuya Fujiwara ◽  
Taizo Uchimoto ◽  
Kenkichi Saito ◽  
Naoki Tanda ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Propensity Score ◽  
Radiographic Progression ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
Castration Resistant ◽  
Psa Response

Background: There is emerging evidence that radiographic progression-free survival (rPFS) is highly correlated with overall survival (OS), potentially serving as an indicator of treatment outcome for castration-resistant prostate cancer (CRPC). The objective of this study is to assess rPFS and prostate specific antigen (PSA) response in sequential treatment using androgen signaling inhibitors (ASIs) including abiraterone and enzalutamide in newly diagnosed CRPC. Methods: Propensity score matching was performed to reduce bias by confounding factors between first-line ASIs. The primary endpoints of the study included rPFS, time to PSA progression (TTPP), and PSA response. Results: A paired-matched group of 184 patients were identified. From the initiation of first-line ASIs, there was no significant difference in rPFS, TTPP, and PSA response between treatment arms. From the initiation of second-line ASIs, enzalutamide following abiraterone consistently exhibited longer rPFS (median: 7 and 15 months, p = 0.04), TTPP, and better PSA response compared to the reverse, whereas OS did not reach significance (median: 14 and 23 months, p = 0.35). Conclusion: Although the effect of ASIs as the first line was similar, the extent of cross-resistance might differ towards less resistance in enzalutamide following abiraterone than the reverse.

scholarly journals Corticosteroid switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients with biochemical progression on abiraterone acetate plus prednisone

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhenyu Yang ◽  
Yuchao Ni ◽  
Diwei Zhao ◽  
Yijun Zhang ◽  
Jun Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Prognostic Predictors ◽  
Castration Resistant ◽  
Risk Stratification Tool ◽  
Psa Response ◽  
Biochemical Progression

Abstract Background To assess the efficacies and potential predictors of a corticosteroid switch in metastatic castration-resistant prostate cancer (mCRPC) patients with biochemical progression on abiraterone acetate plus prednisone (A + P). Methods Patients with mCRPC treated between April 2016 and August 2020, who experienced biochemical progression on A + P and then switched to A plus dexamethasone (D), were retrospectively identified. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were PSA response, overall survival (OS), and safety. Results One hundred and thirty consecutive cases were enrolled. The median PFS and OS on A + D were 5.0 and 18.7 months, respectively. The best PSA decline of ≥50% (PSA50) and ≥ 30% (PSA30) were observed in 29.2 and 46.2% patients, respectively. Lower PSA at corticosteroid switch (≤ 20 ng/mL; median PFS, HR 0.63, p = 0.019; median OS, HR 0.38, p = 0.001) and longer mCRPC-free survival (≥ 18 months; median PFS, HR 0.61, p = 0.013; median OS, HR 0.51, p = 0.015) were identified as independent prognostic predictors associated with longer PFS and OS. A risk stratification tool was developed to select candidates for corticosteroid switch based on the independent prognostic predictors of PFS and OS. Conclusions A corticosteroid switch from prednisone to dexamethasone is effective for mCRPC which progressed on A + P treatment. Patients with lower PSA at corticosteroid switch and/or longer mCRPC-free survival may gain more benefits by the corticosteroid switch.

Multicenter prospective study of switching from GnRH agonists to GnRH antagonist for patients with early stage of castration resistant prostate cancer as a second-line hormonal therapy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 183-183
Author(s):  
Yumiko Yokomizo ◽  
Narihiko Hayashi ◽  
Akitoshi Takizawa ◽  
Kazuki Kobayashi ◽  
Jun-ichi Ohta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gnrh Agonist ◽  
Hormonal Therapy ◽  
Gnrh Antagonist ◽  
Early Stage ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Psa Response

183 Background: It was reported that GnRH antagonist could extend progression free survival for prostate cancer patients significantly longer than GnRH agonist in a first line hormonal therapy. However, the usefulness of switching from GnRH agonist to GnRH antagonist as a second hormonal therapy remains obscure. We performed a multicentral prospective study to investigate whether the switching from GnRH agonist to GnRH antagonist (degalerix) for patients with castration resistant prostate cancer (CRPC) as the 2nd line hormonal therapy was effective. Methods: 37 patients who were pathologically diagnosed as prostatic adenocarcinoma and developed CRPC after 1st line hormonal therapy with GnRH agonist plus anti-androgens were enrolled. After confirming anti-androgen withdrawal syndrome, they were treated with switching from GnRH agonists to degalerix. The primary endpoint was PSA response (PSA decline or up to 10% over baseline PSA). Secondary endpoints were the time to 25% PSA increase from the baseline (PSA response time), PSA progression free survival (PPFS), the time to treatment failure, cancer specific survival, radiographic PFS (rPFS), and safety. Results: Mean age was 76 years old, super high risk; 20 cases (54.1%), high risk; 11 cases (29.7%), intermediate risk; 5 cases (13.5%), low risk; one case (2.7%). PSA responder rate was 24.3% (9 cases). In responders, the median PSA response time was 5.75 months, the median PPFS was 1.77 months, and rPFS rate at 3 months was 96%. Regarding safety, only 2 cases (5.4%) showed G3 of AE. The PSA response had no relationship with the change of serum testosterone, LH nor FSH. Conclusions: The effectiveness of switching from GnRH agonist to GnRH antagonist showed to be limited. Although no predictive factor of the switching was recognized, some long-term responders were seen. We expect the possibility of switching to GnRH antagonist for patients in the early stage of CRPC, especially non-metastatic status. Clinical trial information: UNKNOWN.

scholarly journals Overexpression of CXCR7 is a Novel Indicator for Enzalutamide Resistance in Castration-Resistant Prostate Cancer Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yong Luo ◽  
Qiankun Li ◽  
Xiaobing Yang ◽  
Dechao Wei ◽  
Bingfu Feng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Median Time ◽  
Progression Free Survival ◽  
Negative Group ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Positive Group ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Psa Response

Background. To evaluate whether the overexpression of chemokine receptor-7 (CXCR7) in prostatic tissues obtained from men with Castration-Resistant Prostate Cancer (CRPC) is associated with resistance to enzalutamide (Enza). Methods. Based on the inclusion criteria of CRPC in EAU guidelines, all eligible patients treated in our hospital from January 2015 to December 2019 were included. Cases underwent radical prostatectomy, docetaxel-based chemotherapy, or new endocrine therapies (including Enza or abiraterone), and cases with severe cardiopulmonary disease or other malignant tumors were excluded. After immunohistochemical staining for CXCR7 expression in prostatic biopsy tissues, all enrolled cases were divided into two groups, namely, the CXCR7-positive group and the CXCR7-negative group. And then, PSA response to Enza treatment was recorded in detail and comparatively analyzed. In addition, the Cox proportional hazard modeling and the Kaplan-Meier analysis were used to determine PSA progression-free survival (PSAP-FS) and clinical or radiographic progression-free survival (CRP-FS) in this cohort. Results. A total of 79 CRPC individuals were enrolled and evaluated in this study. Median follow-up durations were 24 months (range, 12-42) in the CXCR7-positive group ( n = 47 ) and 28.5 months (range, 12-42) in the CXCR7-negative group ( n = 32 ). The patients with lower CXCR7 expression showed much better PSA response to Enza treatment. There was 84.4% of CXCR7- cases showing decreasing PSA response, while there were 71.4% in the CXCR7/1+ group and 31.2% in the CXCR7/2+ group, respectively. All patients in the CXCR7/3+ group showed increasing PSA response to Enza treatment. And the percentage of patients whose PSA decreased over 50% is significantly higher in the CXCR7-negative group than in the CXCR7-positive group (68.8% vs. 8.5%, P < 0.001 ), and the percentage of patients whose PSA decreased over 90% is also remarkably higher in the CXCR7-negative group (43.8% vs. 0, P < 0.001 ). The Kaplan-Meier analysis demonstrated that the oncologic outcomes of CXCR7-negative patients were improved much significantly by Enza treatment in comparison with those of CXCR7-positive patients. Significantly increased median PSAP-FS (21 months vs. 6 months, P < 0.0001 ) and CRP-FS (27 months vs. 9 months, P < 0.0001 ) were obtained in the CXCR7-negative group. The further stratified analysis in all CXCR7-positive patients demonstrated that the patients with higher CXCR7 expression showed much worse outcome. The median time of PSAP-FS was 21 months in the CXCR7/1+ group, 9 months in the CXCR7/2+ group, and 6 months in the CXCR7/3+ group, while the median time of CRP-FS was 21 months in the CXCR7/1+ group, 12 months in the CXCR7/2+ group, and 6 months in the CXCR7/3+ group, respectively. Conclusion. Overexpression of CXCR7 induced by an AR antagonist in CRPC patients displays much better treatment response to Enza. CXCR7 might be a novel therapeutic target gene for CRPC patients.

Prognostic impact of prior local therapy in castration-resistant prostate cancer

2021 ◽  
Author(s):  
Mikifumi Koura ◽  
Masaki Shiota ◽  
Shohei Ueda ◽  
Takashi Matsumoto ◽  
Satoshi Kobayashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Line Therapy

Abstract Objective This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). Methods The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. Results In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40–0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. Conclusions This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.

Phase II trial of opaganib in patients with metastatic castration-resistant prostate cancer progressing on abiraterone or enzalutamide (NCT04207255).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS191-TPS191
Author(s):  
Omer Kucuk ◽  
Charles Smith ◽  
Terry Plasse ◽  
Besim Ogretmen ◽  
Shikhar Mehrotra ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Modulation ◽  
Immune Cell ◽  
Progression Free Survival ◽  
Competitive Inhibitor ◽  
Cell Trafficking ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Sphingosine 1 Phosphate

TPS191 Background: Opaganib (Yeliva, ABC294640) is a first-in-class, sphingosine kinase-2 (SK2) selective inhibitor, with anticancer, anti-inflammatory and anti-viral activities. SK2, a lipid kinase catalyzes formation of the lipid signaling molecule sphingosine 1-phosphate (S1P). S1P promotes cancer growth, and proliferation and pathological inflammation, including inflammatory cytokine production. Specifically, by inhibiting the SK2 enzyme, opaganib blocks the synthesis of S1P which regulates fundamental biological processes such as cell proliferation, migration, immune cell trafficking and angiogenesis, and are also involved in immune-modulation and suppression of innate immune responses from T cells. Opaganib is a sphingosine-competitive inhibitor of SK2 and also inhibits dihydroceramide desaturase. Opaganib has antitumor activity against human and murine prostate cancer cell lines, and in xenograft (LNCaP) and syngeneic (MycCAP, TRAMP-C1) murine tumor models. In addition to its target effect of reducing sphingosine-1-phosphate, opaganib reduces both MYC and AR proteins through its kinase-blocking and desaturase-inhibiting properties, respectively. Methods: The study is open to patients with mCRPC who have been treated with at least one newer androgen antagonist (abiraterone or enzalutamide) and no prior chemotherapy for castration-resistant disease. Patients who are failing either abiraterone or enzalutamide may enroll, with the addition of opaganib. The trial design includes brief safety lead-in cohort 1a (abiraterone + opaganib 250 mg Q 12hr, 3/3 enrolled) and 1b (enzalutamide + opaganib 250 mg Q 12hr, 3/3 enrolled). These cohorts have been completed without any DLTs. We are now enrolling cohort 2 (abiraterone + opaganib 500 mg Q 12hr, 0/27 enrolled) and cohort 3 (enzalutamide + opaganib 500 mg Q 12hr, 8/27 enrolled). A total of 60 patients will be enrolled and response will be evaluated after 4 cycles (28 days/cycle) using a composite metric based on PSA, bone scan and RECIST measurements per PCWG3 criteria. Safety and tolerability will be monitored, and dose modifications will be allowed. Primary endpoint is disease control (stable disease or better) after 4 cycles. Secondary endpoints include overall survival, radiographic progression-free survival and PSA progression-free survival. Correlative studies include assessment of quality of life (QOL), circulating MDSCs, immune cells and clones with amplified AR or MYC. Supported by NIH grant P01 CA203628. Clinical trial information: NCT04207255.

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