scholarly journals VEGF-A polymorphisms predict progression-free survival among advanced castration-resistant prostate cancer patients treated with metronomic cyclophosphamide

2013 ◽  
Vol 109 (4) ◽  
pp. 957-964 ◽  
Author(s):  
P Orlandi ◽  
A Fontana ◽  
A Fioravanti ◽  
T Di Desidero ◽  
L Galli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Metronomic Cyclophosphamide

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.

scholarly journals Cabazitaxel for Metastatic Castration-Resistant Prostate Cancer: Retrospective Data Analysis from an Indian Centre

2016 ◽  
Vol 9 (2) ◽  
pp. 506-515
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vamshi Krishna Muddu ◽  
Vijay Maruti Patil ◽  
Kumar Prabhash
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Retrospective Data Analysis ◽  
Grade 3 ◽  
Named Patient Programme

Objective: To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. Methods: mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported. Results: Nine men received cabazitaxel (median: 7 cycles; range: 1–27) under the NPP and were followed until death. Median survival was 14.07 months (1.07–23.80) and progression-free survival was 2.67 months (1.07–20.27). QOL was stable for most patients. Common adverse events (grade ≥3) were neutropenia (n = 8), anaemia (n = 4), and leucopenia (n = 4). Conclusion: These data from 9 patients are consistent with the results reported in the TROPIC study with a manageable safety profile.

YB-1 variant and androgen receptor axis-targeted agents in metastatic castration-resistant prostate cancer patients

2020 ◽  
Vol 21 (13) ◽  
pp. 919-928
Author(s):  
Ana Afonso ◽  
Jani Silva ◽  
Ana Rita Lopes ◽  
Sara Coelho ◽  
Ana Sofia Patrão ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Patients ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Allelic Discrimination ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Increased Risk

Aim: To evaluate the influence of YB-1 rs10493112 variant as a genetic marker for response to second-generation androgen receptor axis-target agents. Methods: A hospital-based cohort study of 78 patients with metastatic castration-resistant prostate cancer was conducted. Genotyping was performed by TaqMan® allelic discrimination technology. Main results: In abiraterone-treated and high-risk patients, YB-1 rs10493112 AA genotype carriers showed lower progression-free survival than C allele genotype patients (4 vs 17 months; p = 0.009). For carriers of AA genotype, multivariate Cox regression analysis revealed a fivefold increased risk of progression (p = 0.035). Conclusion: The study findings suggest that, for metastatic and castration-resistant prostate cancer patients, this polymorphism might be a putative marker for the clinical outcome.

Association Between Second Progression-free Survival (PFS2) and Overall Survival in Metastatic Castration-resistant Prostate Cancer

2020 ◽  
Vol 77 (6) ◽  
pp. 763-766 ◽  
Author(s):  
David Lorente ◽  
Elena Castro ◽  
Rebeca Lozano ◽  
Javier Puente ◽  
Nuria Romero-Laorden ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant

scholarly journals Metastatic Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy: Treatment Patterns From the PROXIMA Prospective Registry

2018 ◽  
pp. 1-12 ◽  
Author(s):  
Hideyuki Akaza ◽  
Giuseppe Procopio ◽  
Choosak Pripatnanont ◽  
Gaetano Facchini ◽  
Sergio Fava ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Real World ◽  
Progression Free Survival ◽  
Treatment Patterns ◽  
Treatment Modalities ◽  
Treatment Sequence ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Previously Treated

Purpose There is a major clinical need to devise an optimal treatment sequence for the multiple therapy options available for patients with metastatic castration-resistant prostate cancer (mCRPC). In the absence of prospective clinical trials, sequencing information can be derived from large, real-world registry studies. Patients and Methods PROXIMA (Treatment Patterns in Patients With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy) is a large, global, prospective registry study evaluating real-world treatment patterns of patients with mCRPC who experience disease progression during or after docetaxel therapy. Patients were enrolled worldwide between 2011 and 2014. Treatments were determined by the treating physicians and recorded in categories of chemotherapy, hormonal therapy, targeted therapy, immunotherapy, and palliative therapy. Treatment sequencing patterns, response to treatment, and types of progression were recorded and analyzed. Progression-free survival and overall survival with different treatment modalities were analyzed using Kaplan–Meier method. Results Treatment patterns were evaluated in 903 patients. Therapy selection was influenced by region. Hormonal therapy (57.5%) and taxane chemotherapy (26.4%) were the most frequently administered first subsequent treatments after docetaxel. Tumor responses to first subsequent treatment were observed in 22.6% of evaluable patients. Overall survival and progression-free survival did not differ significantly across different treatment modalities. Conclusion Identifying an optimal treatment sequence is vital for improving the care of patients with mCRPC. The PROXIMA registry provided a representative sample of global data on real-world treatment patterns for patients with mCRPC previously treated with docetaxel. These data can be used to devise optimal therapy sequences and inform treatment decisions.

Correlation of 18F-fluoride PET response to dasatinib in castration-resistant prostate cancer bone metastases with progression-free survival: Preliminary results from ACRIN 6687.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5003-5003
Author(s):  
Evan Y. Yu ◽  
Fenghai Duan ◽  
Mark Muzi ◽  
Jeremy Gorelick ◽  
Bennett Chin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Pet Imaging ◽  
Progression Free Survival ◽  
Post Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Normal Bone ◽  
Castration Resistant ◽  
Pre Treatment

5003 Background: Dasatinib is a SRC kinase inhibitor that decreases bone turnover in men with metastatic castration-resistant prostate cancer (mCRPC). 18F-fluoride PET was used to evaluate differential response between normal and tumor bone to dasatinib. Methods: Patients with bone mCRPC underwent dynamic 18F-flouride PET imaging prior to and 12 weeks after dasatinib treatment. Up to 5 bone metastases with matching normal bone regions were selected for analysis by SUVmax, Ki, K1and Patlak flux. Their pre-treatment values and change from pre-treatment to post-treatment values were evaluated via generalized estimating equations to predict skeletal-related events (SRE) and via Cox proportional hazards modeling to predict progression-free survival (PFS) with Prostate Cancer Working Group 2 criteria, overall survival and time to SRE. Results: Eighteen patients treated with dasatinib underwent baseline 18F-flouride PET imaging; 12 had follow-up scans allowing assessment of changes due to therapy. Median age for all patients was 69 (range 48-86) years. Significant decrease in SUVmax (p=0.0002) occurred in bone metastases with dasatinib while significant increases in Patlak flux (p=0.0033) occurred in normal bone. Significant differences in changes from tumor bone compared to normal bone in response to dasatinib were noted for SUVmax (p<0.0001). Of 18 patients, 17 have either met progression criteria or death by the time of this analysis. Decrease in tumor bone SUVmax (p=0.019), Ki(p=0.022), and Patlak flux (p=0.034) from pre-treatment to post-treatment correlates with longer PFS. Conclusions: 18F-fluoride PET indicates differential effect of dasatinib on tumor compared to normal bone in men with mCRPC. In patients undergoing pre- and post-dasatinib 18F-fluoride PET imaging a decrease in bone mCRPC fluoride uptake in response to treatment correlates with PFS. Clinical trial information: NCT00936975.

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