scholarly journals Impact of Serum γ-Glutamyltransferase on Overall Survival in Men with Metastatic Castration-Resistant Prostate Cancer Treated with Docetaxel

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5587
Author(s):  
Minami Une ◽  
Kosuke Takemura ◽  
Kentaro Inamura ◽  
Hiroshi Fukushima ◽  
Masaya Ito ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Prognostic Models ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Expression Status

Background: Reports on the prognostic significance of serum γ-glutamyltransferase (GGT) in men with metastatic castration-resistant prostate cancer (mCRPC) are limited. In addition, GGT expression status in cancer tissues has not been well characterized regardless of cancer types. Methods: This retrospective study included 107 consecutive men with mCRPC receiving docetaxel therapy. The primary endpoints were associations of serum GGT with overall survival (OS) and prostate-specific antigen (PSA) response. The secondary endpoint was an association of serum GGT with progression-free survival (PFS). Additionally, GGT expression status was immunohistochemically semi-quantified using tissue microarrays. Results: A total of 67 (63%) men died during follow-up periods (median 22.5 months for survivors). On multivariable analysis, high Log GGT was independently associated with adverse OS (HR 1.49, p = 0.006) as were low hemoglobin (HR 0.79, p = 0.002) and high PSA (HR 1.40, p < 0.001). In contrast, serum GGT was not significantly associated with PSA response or PFS. Moreover, incorporation of serum GGT into established prognostic models (i.e., Halabi and Smaletz models) increased their C-indices for predicting OS from 0.772 to 0.787 (p = 0.066) and from 0.777 to 0.785 (p = 0.118), respectively. Furthermore, there was a positive correlation between serum and tissue GGT levels (ρ = 0.53, p = 0.003). Conclusions: Serum GGT may be a prognostic biomarker in men with mCRPC receiving docetaxel therapy. GGT overexpression by prostate cancer cells appears to be responsible for the elevation of GGT in the serum.

Circulating microRNAs associated with docetaxel-resistant castration resistant prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 44-44
Author(s):  
Lisa Horvath ◽  
Hui-Ming Lin ◽  
Lesley Castillo ◽  
Kate Lynette Mahon ◽  
Karen Chiam ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Specific Antigen ◽  
Family Members ◽  
Response To Therapy ◽  
Circulating Microrna ◽  
Castration Resistant Prostate Cancer ◽  
Circulating Micrornas ◽  
Castration Resistant ◽  
Psa Response

44 Background: Despite a range of new treatments, docetaxel (DTX) remains the first-line chemotherapy for castration-resistant prostate cancer (CRPC). However, only 50% of patients respond to docetaxel at the cost of potentially significant toxicity. Therefore, there is a need for new biomarkers to identify early response to therapy. This study aims to determine if circulating microRNAs are associated with DTX chemotherapy outcome in CRPC. Methods: Global microRNA profiling was performed on DTX-resistant and sensitive cell lines to identify candidate circulating microRNA biomarkers. Custom Taqman Array MicroRNA cards measured the levels of 46 candidate microRNAs in plasma/serum from 97 CRPC patients, collected pre- and three weeks post-cycle one of DTX. Responses were defined by the PCWG1 serum prostate-specific antigen (PSA) response criteria; partial response (PR), stable disease (SD), progressive disease (PD). Multiple T-test, Mann-Whitney U, Kaplan-Meier, Receiver Operating Characteristic (ROC), and Cox regression analyses were used to assess the associations between microRNA levels and clinical outcomes. Results: Eighteen microRNAs were associated with PSA response or overall survival (p<0.05). DTX non-responders (PD+SD) and patients with shorter survival had high pre-DTX levels of miR-200 family members (miR-200a, miR-200b, miR-200c, miR-429; p<0.05), or decreased/unchanged post-DTX levels of miR-17 family members (miR-19b, miR-20a, miR-20b; p<0.05). The combined levels of miR-20a, miR-146a, miR-200b, miR-200c, miR-222, and miR-301b predicted PSA response (ROC AUC 0.74, 95% CI 0.64-0.84). Pre-DTX miR-200a levels (HR 3.0, 95%CI 1.6-5.8; p=0.001) and post-DTX change in miR-20a (HR 3.4, 95%CI 1.8-6.3; p=0.0002) were independent predictors of overall survival when modeled with hemoglobin levels (HR 2.6, 95%CI 1.4-5.1; p=0.02), PSA response (HR 2.1, 95%CI 1.1-3.9; p=0.03), and visceral metastases (HR 2.0, 95%CI 1.1-3.5; p=0.03). Conclusions: Circulating microRNAs are potential early predictors of DTX chemotherapy outcome and may be useful in stratifying patients in future clinical trials. These microRNAs may also be involved in DTX resistance and represent potential therapeutic targets.

scholarly journals Three-month early change in prostate-specific antigen levels as a predictive marker for overall survival during hormonal therapy for metastatic hormone-sensitive prostate cancer

2021 ◽  
Author(s):  
Shotaro Nakanishi ◽  
Masato Goya ◽  
Mitsuyoshi Tamaki ◽  
Takuma Oshiro ◽  
Seiichi Saito
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Prostate Specific Antigen ◽  
Characteristic Curve ◽  
Specific Antigen ◽  
Predictive Marker ◽  
Castration Resistant Prostate Cancer ◽  
Pretreatment Level ◽  
Castration Resistant ◽  
Hormone Sensitive

Abstract Objective: To date, there are no useful markers for predicting the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the effect of early changes in prostate-specific antigen (PSA) levels after androgen deprivation therapy (ADT) on castration-resistant prostate cancer (CRPC) progression and overall survival (OS) in mHSPC patients. Results: In 71 primary mHSPC patients treated with ADT, the median times to CRPC and OS were 15 months and 92 months, respectively. In multivariate analysis, a Gleason score of ≥8 (p = 0.004), an extent of disease value (EOD) of ≥2 (p = 0.004), and a 3-month PSA level >1% of the pretreatment level (p = 0.017) were independent predictors of shorter time to CRPC. The area under the receiver operating characteristic curve was feasible at 0.822. For OS, a 3-month PSA level >1% of the pretreatment level was an independent predictor of time to CRPC (p = 0.004).Three factors were independent predictors of shorter time to CRPC. A 3-month PSA level >1% of the pretreatment level correlated with poor a prognosis.

scholarly journals Overall Survival of Black and White Men With Metastatic Castration-Resistant Prostate Cancer Treated With Docetaxel

2019 ◽  
Vol 37 (5) ◽  
pp. 403-410 ◽  
Author(s):  
Susan Halabi ◽  
Sandipan Dutta ◽  
Catherine M. Tangen ◽  
Mark Rosenthal ◽  
Daniel P. Petrylak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Black Men ◽  
Performance Status ◽  
Specific Antigen ◽  
White Men ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Black And White ◽  
Castration Resistant

Purpose Several studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist for men with advanced prostate cancer. The primary goal of this analysis was to compare the OS in black and white men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in phase III clinical trials with docetaxel plus prednisone (DP) or a DP-containing regimen. Methods Individual participant data from 8,820 men with mCRPC randomly assigned in nine phase III trials to DP or a DP-containing regimen were combined. Race was based on self-report. The primary end point was OS. The Cox proportional hazards regression model was used to assess the prognostic importance of race (black v white) adjusted for established risk factors common across the trials (age, prostate-specific antigen, performance status, alkaline phosphatase, hemoglobin, and sites of metastases). Results Of 8,820 men, 7,528 (85%) were white, 500 (6%) were black, 424 (5%) were Asian, and 368 (4%) were of unknown race. Black men were younger and had worse performance status, higher testosterone and prostate-specific antigen, and lower hemoglobin than white men. Despite these differences, the median OS was 21.0 months (95% CI, 19.4 to 22.5 months) versus 21.2 months (95% CI, 20.8 to 21.7 months) in black and white men, respectively. The pooled multivariable hazard ratio of 0.81 (95% CI, 0.72 to 0.91) demonstrates that overall, black men have a statistically significant decreased risk of death compared with white men ( P < .001). Conclusion When adjusted for known prognostic factors, we observed a statistically significant increased OS in black versus white men with mCRPC who were enrolled in these clinical trials. The mechanism for these differences is not known.

Abiraterone in patients with metastatic castration-resistant prostate cancer progressing after docetaxel and MDV3100.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4554-4554 ◽  
Author(s):  
Ecaterina Ileana ◽  
Yohann Loriot ◽  
Laurence Albiges ◽  
Christophe Massard ◽  
Aurore Blesius ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Specific Antigen ◽  
Patient Characteristics ◽  
Preliminary Evidence ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Symptom Response ◽  
Psa Response ◽  
Metastatic Sites

4554 Background: Chemotherapy with docetaxel is the standard first-line treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). In patients progressing after docetaxel, both abiraterone and MDV3100 have yielded improved survival for patients with mCRPC. The efficacy of abiraterone in patients pre-treated with MDV 3100 is unknown. Methods: We investigated abiraterone-prednisone in 24 patients with cancer progression after docetaxel followed by MDV3100. All patients received abiraterone 1000 mg/day plus prednisone 10mg/day. Prostate-specific antigen (PSA) response, symptom response, and time to progression were assessed. Results: Patient characteristics were as follows: median age: 74 years (53-84), median PSA: 108 ng/mL (2-2541), metastatic sites: bone: all 24 patients, liver/lung: 6 patients (25%), and lymph nodes : 9 patients (38%). Five patients (21%) had a PSA decrease on abiraterone-prednisone. Three patients (13%) achieved a PSA response, defined as a decrease of >50% in PSA, confirmed after≥ 4 weeks. The duration of PSA response was 2, 3 and 4.5 months. Six patients (29%) had a symptomatic response on the pain score and analgesic consumption was decreased. Treatment was well tolerated. Abiraterone-prednisone was discontinued in one patient due to edema and hypokaliemia. Conclusions: This study shows preliminary evidence that abiraterone-prednisone yields activity in patients with mCRPC pretreated with docetaxel and MDV3100.

The effect of prior abiraterone (Abi) use on the activity of enzalutamide (Enza) in men with mCRPC.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 18-18 ◽  
Author(s):  
Heather H. Cheng ◽  
Rosa Nadal ◽  
Roman Gulati ◽  
Arun Azad ◽  
Przemyslaw Twardowski ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Subsequent Treatment ◽  
Significant Response ◽  
Castration Resistant Prostate Cancer ◽  
Steroid Use ◽  
Castration Resistant ◽  
Disease Characteristics ◽  
Psa Response ◽  
Time Of Presentation

18 Background: Enzalutamide (Enza) and abiraterone (Abi) are next generation hormonal agents for metastatic castration resistant prostate cancer (mCRPC). Whether these agents can be effectively sequenced is not yet well understood. Results of retrospective analyses of Abi after prior Enza have demonstrated modest responses of brief duration, suggesting common resistance pathways. Here, we retrospectively analyze response to Enza with or without prior Abi treatment. Methods: We retrospectively reviewed 195 patients from seven academic centers treated with Enza between January 2009 and August 2013. Data were collected on disease characteristics, prior therapies, and prostate-specific antigen (PSA) values at baseline and while on treatment. Logistic regression was used to evaluate association between 30% or greater PSA decline on Enza and either prior Abi treatment or 30% or greater PSA decline on prior Abi after accounting for potential confounders. Results: One hudred eighty three patients had non-missing PSA starting and nadir values on Enza, with starting PSA median 102.0 (range 1.1–5007.0) ng/mL. Overall, 42% (76 of 183) of Enza-treated patients achieved a 30% or greater PSA decline, with 39% (58 of 150) response among prior Abi-treated patients and 55% (18 of 33) response among Abi-naïve patients. Of 79 patients who lacked significant response to prior Abi, 30% (25 of 79) achieved a 30% or greater PSA decline and 19% (15 of 79) achieved a 50% or greater PSA decline with subsequent Enza. Odds of achieving a 30% or greater PSA response on Enza was 2.3 times higher for Abi-naïve patients versus prior Abi-treated patients (95% CI 1.0–5.5, P=0.06) and 1.9 times higher for Abi-responders vs Abi-non-responders (95% CI 1.0–3.7, P=0.06) after adjusting for prior docetaxel and concurrent steroid use. Conclusions: In this multi-center retrospective study, 39% of patients achieved a 30% or greater PSA decline with Enza after prior Abi treatment. While the activity of Enza appears to be blunted in the post-Abi setting, PSA declines still occur in a meaningful proportion of patients. Notably, 30% of patients without significant response to prior Abi responded to subsequent treatment with Enza, suggesting a subset of men with distinct biological resistance pathways. Data will be updated at the time of presentation.

Relationship between abiraterone exposure, prostate-specific antigen (PSA) kinetics, and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) .

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 39-39 ◽  
Author(s):  
Steven Xu ◽  
Charles J. Ryan ◽  
Kim Stuyckens ◽  
Matthew R. Smith ◽  
Fred Saad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Specific Antigen ◽  
Maximum Effect ◽  
Castration Resistant Prostate Cancer ◽  
Modeling Framework ◽  
Psa Kinetics ◽  
Castration Resistant ◽  
Survival Modeling ◽  
The Relationship

39 Background: Abiraterone, the active metabolite of abiraterone acetate (AA), is an effective androgen biosynthesis inhibitor for patients with metastatic castration-resistant prostate cancer (mCRPC). We conducted a sequential exposure-biomarker-survival modeling analysis to explore the relationship between prostate-specific antigen (PSA) kinetics and overall survival (OS) and to establish the exposure response for PSA kinetics and OS in chemotherapy-naïve and -pretreated patients with mCRPC following AA administration. Methods: The exposure-PSA-survival modeling framework was based on two phase III studies, COU-AA-301 (chemotherapy-pretreated, N = 1184) and COU-AA-302 (chemotherapy-naïve, N = 1081), and included a mixed-effects tumor growth inhibition (TGI) model to describe PSA dynamics in response to AA and a Cox proportional hazards survival model to evaluate the relationship between relative risk of death and PSA dynamic end points. Results: The TGI model best described the longitudinal PSA dynamics following AA treatment. Abiraterone exposure significantly increased PSA decay rate (maximum effect of 2.72, p < 0.0001). The estimated concentration for 50% of the maximum effect (EC50) was 4.75 ng/mL. The abiraterone effect on PSA kinetics was similar in chemotherapy-naïve and -pretreated subjects, and approximately 90% of subjects had a steady-state concentration greater than the EC50. All model-predicted PSA metrics were strongly associated with OS in both populations; model-based post-treatment PSA doubling time showed the strongest association (hazard ratios approximately 0.9 in both populations). Simulations showed that the modeling framework could accurately predict the survival outcome for both studies. Conclusions: The analysis revealed a similar effect of abiraterone on PSA kinetics and association between PSA kinetics and OS in chemotherapy-naïve and -pretreated subjects, providing additional evidence for surrogacy of PSA kinetics and the use of PSA end points to indicate clinical benefit of abiraterone in subjects with mCRPC regardless of prior chemotherapy. Furthermore, the study confirmed that the recommended 1,000 mg/d dose of AA leads to adequate clinical exposure above the effective level. Clinical trial information: NCT00638690, NCT00887198.

scholarly journals Phase II Trial of Bevacizumab, Thalidomide, Docetaxel, and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer

2010 ◽  
Vol 28 (12) ◽  
pp. 2070-2076 ◽  
Author(s):  
Yang-Min Ning ◽  
James L. Gulley ◽  
Philip M. Arlen ◽  
Sukyung Woo ◽  
Seth M. Steinberg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Combination Therapy ◽  
Phase Ii ◽  
Specific Antigen ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Time To Progression ◽  
Castration Resistant ◽  
Phase Ii Studies

Purpose We previously demonstrated that thalidomide appears to add to the activity of docetaxel in metastatic castration-resistant prostate cancer (CRPC). Phase II studies combining docetaxel with bevacizumab have had substantial antitumor activity. We hypothesized that the combination of docetaxel plus these antiangiogenic drugs with different targets would have substantial clinical activity. To explore safety and efficacy, this was tested in mice and in human patients. Patients and Methods Preclinical efficacy of the combination therapy was evaluated in PC3 xenograft mice. Sixty patients with progressive metastatic CRPC received intravenous docetaxel and bevacizumab plus oral thalidomide and prednisone. The primary end point was a prostate-specific antigen (PSA) decline of ≥ 50%. Secondary end points included time to progression, overall survival, and safety. Results In the mouse model, combination therapy of docetaxel, bevacizumab, and thalidomide inhibited tumor growth most effectively. In the clinical trial, 90% of patients receiving the combination therapy had PSA declines of ≥ 50%, and 88% achieved a PSA decline of ≥ 30% within the first 3 months of treatment. The median time to progression was 18.3 months, and the median overall survival was 28.2 months in this group with a Halabi-predicted survival of 14 months. While toxicities were manageable, all patients developed grade 3/4 neutropenia. Conclusion The addition of bevacizumab and thalidomide to docetaxel is a highly active combination with manageable toxicities. The estimated median survival is encouraging, given the generally poor prognosis of this patient population. These results suggest that definitive clinical trials combining antiangiogenic agent combinations with docetaxel are warranted to improve treatment outcomes for patients with metastatic CRPC.

scholarly journals Pretreatment neutrophil-to-lymphocyte ratio and Mean Platelet Volume in castration-resistant prostate cancer patients treated with first-line docetaxel

2019 ◽  
Author(s):  
Barbaros Başeskioğlu ◽  
Berna Bozkurt Duman ◽  
Bülent Yıldız ◽  
Timuçin Çil ◽  
Murat Dinçer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mean Platelet Volume ◽  
Specific Antigen ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Platelet Volume ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Castration Resistant ◽  
Psa Response

Abstract Background:Patients who have evidence of disease progression (eg, increase in serum prostate-specific antigen [PSA], new metastases, progression of existing metastases) while being managed with androgen deprivation therapy (ADT) are considered to have castration-resistant disease. Docetaxel (75 mg/m2) given every three weeks in combination with daily prednisone (5 mg twice a day) significantly prolonged overall survival compared with mitoxantrone plus prednisone in the TAX 327 phase III trial [3]. Based upon those results, docetaxel plus prednisone has become the standard initial regimen when chemotherapy is indicated for CRPC Methods: Inflammation-based markers, such as the Neutrophile/Lymphocyte Ratio (NLR), are widely available and inexpensive measurements that are easy to integrate into pretreatment evaluation. Mean platelet volume (MPV) is a marker of activated platelets is associated some types of cancer including ovarian, gastric cancer. We retrospectively evaluated the predictive impact of neutrophil-lymphocyte ratio (NLR) and MPV as a marker for in men with progressive metastatic castration resistant prostate cancer (mCRPC) following docetaxel.Results: A significant correlation was not observed between NLR and PSA response. A significant correlation was not also observed between MPV and PSA response.There no correlation was found between MPV and NLR with total PSA level and response (p:0.355, p:0.673 respectively)Conclusion: . In our study; We didn’t show any correlation between MWP level, NLR ratio and response to Docetaxel therapy A significant correlation was not also observed between NLR , MPV and PSA response.

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