The effect of therapeutic anticoagulation on overall survival (OS) in men receiving docetaxel chemotherapy for metastatic castration-resistant prostate cancer (mCRPC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 28-28
Author(s):  
Caroline F. Pratz ◽  
Robert A. Brodsky ◽  
Emmanuel S. Antonarakis
Keyword(s):  
Proportional Hazards ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Therapeutic Anticoagulation ◽  
Antitumor Potential ◽  
Docetaxel Chemotherapy

28 Background: Anticoagulants have been postulated to possess antitumor activity, although clinical data supporting this claim are conflicting. We sought to examine the effect of therapeutic anticoagulation on OS in men with mCRPC receiving first-line docetaxel chemotherapy. Methods: We retrospectively reviewed the records of 247 consecutive mCRPC patients who received first-line docetaxel chemotherapy between 1/1/1998 and 1/1/2010. Information on anticoagulant use, type of anticoagulant administered, indication for anticoagulation, and duration of anticoagulation were captured. Univariate and multivariable Cox proportional hazards regression models were developed to investigate the effect of anticoagulant use on OS. Results: In all, 29/247 men (11.7%) received anticoagulation (LMW heparin: 17/247; warfarin: 12/247). The indication was DVT in 15/247, PE in 9/247, and both DVT and PE in 5/247 men. In univariate analysis, anticoagulant use was associated with improved OS (any anticoagulant, HR 0.61 [95%CI 0.40–0.94] P=0.024; LMW heparin, HR 0.58 [95%CI 0.34–0.99] P=0.048; warfarin, HR 0.82 [95%CI 0.55–1.28] P=0.23). Median OS was 20.9 mo (with any anticoagulant) versus 17.1 mo (with no anticoagulant). In multivariable analysis, anticoagulant use remained a significant predictor of OS after adjusting for other prognostic factors (Table). Conclusions: Anticoagulant use is an independent predictor of OS in men with mCRPC receiving docetaxel. This finding is surprising given that the occurrence of venous thrombosis might be expected to negatively influence OS. If validated, these data may provide the impetus to explore the antitumor potential of anticoagulants in prospective clinical trials. [Table: see text]

scholarly journals Oncological outcomes of metastatic castration resistant prostate cancer (mCRPC) treated with different therapies sequences after completion of docetaxel: a retrospective study in Songklanagarind Hospital

2021 ◽  
Vol 42 (2) ◽  
pp. 131-137
Author(s):  
Isaris Chaokhamin ◽  
◽  
Worapat Attawettayanon ◽  
Virote Chalieopanyarwong ◽  
Monthira Tanthanuch ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Abiraterone Acetate ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Oncological Outcomes ◽  
Castration Resistant ◽  
Docetaxel Chemotherapy

Objective: Many treatment options of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel chemotherapy have proved efficacious in clinical trials but, to date, knowledge regarding oncological outcomes is limited. Materials and Methods: We assessed the oncological outcome of 4 drugs (abi- raterone acetate, cabazetaxel, enzalutamide and ketoconazole) in a normal clinical setting in a university-based hospital. Our cohort consisted of 69 patients with post-docetaxel mCRPC. The primary endpoint was overall survival (OS). The secondary endpoint was predicted factor associated overall survival with all sec- ond-line mCRPC treatment outcomes according to the Cox proportional hazards regression model. Results: This cohort consisted of 69 patients with progressive mCRPC after docetaxel chemotherapy. Median overall survival following treatment with abiraterone acetate and ketoconazole was 25.92 and 9.59 months respectively (p < 0.05). Overall survival rates at 1-year following abiraterone acetate, cabazetaxel, enzalutamide and ketoconazole therapy were 76.3%, 83.3%, 100% and 41.9%, respectively. Multivariable analysis found that abiraterone acetate, cabazitaxel and enzalutamide significantly improved survival in comparison to ketoconazole (p < 0.001). Conclusion: Analysis of overall survival following second-line treatment of mCRPC post docetaxel in our study statistically significantly confirmed that abiraterone acetate, cabazitaxel and enzalutamide improve overall survival in comparison to ketoconazole. The study also found that enzalutamide treatment resulted in better outcomes in comparison to the other drugs.

scholarly journals Prognostic and predictive clinical factors in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel

2018 ◽  
Vol 12 (8) ◽  
Author(s):  
Daniel W. Yokom ◽  
John Stewart ◽  
Nimira S. Alimohamed ◽  
Eric Winquist ◽  
Scott Barry ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Response ◽  
Proportional Hazards ◽  
Treatment Options ◽  
Multivariable Analysis ◽  
Specific Antigen ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Clinical Factors ◽  
Castration Resistant

Introduction: Cabazitaxel is one of several treatment options available for patients with metastatic castration-resistant prostate cancer who have progressed on docetaxel. Little is known about clinical factors that influence prognosis or treatment response for patients receiving cabazitaxel. Identifying prognostic and predictive factors could contribute to the optimal selection of patients for treatment after docetaxel.Methods: A retrospective review of patients enrolled on the cabazitaxel Canadian Early Access Program (C-EAP) was performed. Clinical factors were analyzed by univariable and multivariable Cox proportional hazards and logistic regression analysis to identify independent predictors of prognosis and response.Results: Forty-five patients from five centres in Canada were included in this study. On multivariable analysis, lower hemoglobin was associated with shorter survival. No other factors were independently associated with survival, prostate-specific antigen (PSA) response, or primary PSA progression.Conclusions: Clinical factors predicting survival or treatment response were not identified for men with castration-resistant prostate cancer receiving cabazitaxel. Larger studies may be necessary to identify clinical factors and biomarkers that identify whether patients should or should not receive cabazitaxel.

scholarly journals The development and validation of a prognostic nomogram and nomogram application software among men treated with abiraterone acetate and/or enzalutamide for metastatic castration-resistant prostate cancer

2020 ◽  
Author(s):  
Takashi Kawahara ◽  
Yusuke Saigusa ◽  
Shuko Yoneyama ◽  
Masashi Kato ◽  
Ippei Kojima ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Abiraterone Acetate ◽  
Cox Proportional Hazards ◽  
Mobile App ◽  
Application Software ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Abstract BACKGROUND:With widespread medication choices for metastatic castration-resistant prostate cancer (mCRPC) is now available, on the other hand biomarker to predict the efficacy of each mCRPC treatment has not been established.Objective:This study developed prognostic nomogram to predict prognosis in CRPC patients who received abiraterone acetate (ABI) and/or enzalutamide (ENZ).Design, Setting, and Participants:A total of 568 mCRPC patients received ABI and/or ENZ from 2012 to 2017 were enrolled in this study. We developed prognostic nomogram based on the risk factors by Cox proportional hazards regression model.Outcome Measurements and Statistical Analysis:The nomogram was also assessed for discriminatory ability with the concordance index (C-index). We repeated 5-fold cross-validation 2000 times to estimate the C-index and reported the means of the estimated C-index for the training and validation sets. And we also developed nomogram application software (app) based on this nomogram.Results and Limitations:The median overall survival (OS) was 24.7 months. A multivariable analysis showed that the time to CRPC, pre-chemotherapy, baseline PSA, baseline ALP, and baseline LDH were independent risk factors for the OS (HR: 0.521, 1.681, 1.439, 1.827, 12,123, p:0.001, 0.001, <0.001, 0.019, <0.001)). C-index was 0.72 in training cohort and 0.71 in validation cohort.CONCLUSIONS:We developed nomograms to predict the OS for Japanese mCRPC patients who received ABI and/or ENZ. The advent of mCRPC prognosis prediction app will facilitate greater accessibility for clinical use.Patient SummaryThis study developed and validated a nomogram for predicting the prognosis of mCRPC patients who receive ABI/ENZ treatment using clinical information. This study also developed mobile app to facilitate clinical usage.

scholarly journals The Development and Validation of a Prognostic Nomogram and Nomogram Application Software Among Men Treated with Abiraterone Acetate and/or Enzalutamide for Metastatic Castration-resistant Prostate Cancer

2020 ◽  
Author(s):  
Takashi Kawahara ◽  
Yusuke Saigusa ◽  
Shuko Yoneyama ◽  
Masashi Kato ◽  
Ippei Kojima ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Abiraterone Acetate ◽  
Cox Proportional Hazards ◽  
Mobile App ◽  
Application Software ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Abstract Background:With widespread medication choices for metastatic castration-resistant prostate cancer (mCRPC) is now available, on the other hand biomarker to predict the efficacy of each mCRPC treatment has not been established.Objective:This study developed prognostic nomogram to predict prognosis in CRPC patients who received abiraterone acetate (ABI) and/or enzalutamide (ENZ).Design, Setting, and Participants:A total of 568 mCRPC patients received ABI and/or ENZ from 2012 to 2017 were enrolled in this study. We developed prognostic nomogram based on the risk factors by Cox proportional hazards regression model.Outcome Measurements and Statistical Analysis:The nomogram was also assessed for discriminatory ability with the concordance index (C-index). We repeated 5-fold cross-validation 2000 times to estimate the C-index and reported the means of the estimated C-index for the training and validation sets. And we also developed nomogram application software (app) based on this nomogram.Results and Limitations:The median overall survival (OS) was 24.7 months. A multivariable analysis showed that the time to CRPC, pre-chemotherapy, baseline PSA, baseline ALP, and baseline LDH were independent risk factors for the OS (HR: 0.521, 1.681, 1.439, 1.827, 12,123, p:0.001, 0.001, <0.001, 0.019, <0.001)). C-index was 0.72 in training cohort and 0.71 in validation cohort.Conclusion:We developed nomograms to predict the OS for Japanese mCRPC patients who received ABI and/or ENZ. The advent of mCRPC prognosis prediction app will facilitate greater accessibility for clinical use.Patient SummaryThis study developed and validated a nomogram for predicting the prognosis of mCRPC patients who receive ABI/ENZ treatment using clinical information. This study also developed mobile app to facilitate clinical usage.

scholarly journals Disparity in outcomes of melanoma adjuvant immunotherapy by demographic profile

2020 ◽  
Vol 7 (2) ◽  
pp. MMT43
Author(s):  
Alexandra Ikeguchi ◽  
Michael Machiorlatti ◽  
Sara K Vesely
Keyword(s):  
Survival Benefit ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Demographic Factors ◽  
Cox Proportional Hazards ◽  
Adjuvant Immunotherapy ◽  
Node Positive ◽  
Melanoma Patients ◽  
The Impact

Background: Randomized comparisons have demonstrated survival benefit of adjuvant immunotherapy in node-positive melanoma patients but have limited power to determine if this benefit persists across various demographic factors. Materials & methods: We assessed the impact of demographic factors on the survival benefit of adjuvant immunotherapy in a database of 38,189 node-positive melanoma patients using the Kaplan–Meier method and Cox proportional hazards models. Results: All assessed demographic factors other than race significantly impacted survival of node-positive melanoma patients in univariate analysis. In multivariable analysis, only the age group interacted with immunotherapy. Conclusion: Analysis of this large database of unselected node-positive melanoma patients demonstrated a positive survival benefit of immunotherapy across all demographic factors assessed and the impact was greater for patients 65 years of age and older.

Use of epirubicin, carboplatin, and 5-fluorouracil (ECarboF) as a second-line treatment in metastatic castration-resistant prostate cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 173-173
Author(s):  
U. B. McGovern ◽  
S. J. Harland
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Performance Status ◽  
Median Number ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Docetaxel Chemotherapy ◽  
Line Chemotherapy

173 Background: ECarboF chemotherapy is an active first line chemotherapy treatment for metastatic prostate cancer. We have now investigated its efficacy and toxicity in patients who have progressed during or after docetaxel chemotherapy. Methods: 37 patients with metastatic prostate cancer who had received ECarboF chemotherapy were retrospectively reviewed from a five year period (2005-2010). All patients had previously received first-line docetaxel chemotherapy and had either progressed following treatment (n=17) or were docetaxel refractory (n=20). Patients received epirubicin 50mg/m2 iv d1, carboplatin (AUC 5) d1, fluorouracil 440mg/m2 d1, d15 and folinic acid 20mg/m2 d1, d15 on a q4w cycle. 20% dose reductions were made for the first cycle in patients with poorer performance status. PSA was measured before each cycle of treatment and all patients were assessed for toxicity. Results: Patients had a median age of 70 years (range 48-77), median baseline PSA of 226.5 ng/mL (range 9.6-1,580) and the median number of ECarboF chemotherapy cycles received was 6 (range 1-10). 65% (n=24) of patients were ECOG 0-1, the remaining 35% (n=13) were ECOG 2-3. 16% (n=6) patients had a ≥ 30% decline in PSA and 16% (n=6) patients had a ≥ 50% decline in PSA. 35% (n=13) of patients experienced grade 3/4 toxicity, most commonly anaemia (13.5%), neutropenia (13.5%) and thrombocytopenia (8.1%) with one treatment related death (neutropenic sepsis) during the five year period analysed. Median time to PSA progression was 5.1 months. Conclusions: ECarboF has activity with acceptable toxicity post docetaxel in the treatment of metastatic castration resistant prostate cancer. Although PSA response rates are modest, the time to progression is comparable to that of more toxic regimens. ECarboF should be considered as an active second-line chemotherapy regimen. No significant financial relationships to disclose.

Association between radiographic response and overall survival in men with metastatic castration-resistant prostate cancer receiving chemotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 118-118
Author(s):  
G. Sonpavde ◽  
G. R. Pond ◽  
W. R. Berry ◽  
R. De Wit ◽  
M. A. Eisenberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Objective Assessment ◽  
Objective Response ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier

118 Background: In men with metastatic castration resistant prostate cancer (CRPC),the association of measurable tumor responses with overall survival (OS) is unknown. We retrospectively evaluated the TAX327 phase III trial to study this relationship. Methods: Eligible patients for this analysis included those with WHO-defined measurable metastatic disease randomized to receive either docetaxel or mitoxantrone. OS was estimated using the Kaplan-Meier method and the prognostic relationship of WHO-defined radiologic response with OS was performed using Cox proportional hazards regression. Landmark analyses evaluated survival from baseline and 2, 3, 4 and 6 months after baseline. Results: Four hundred and twelve patients enrolled on the TAX327 trial had measurable tumors. Thirty-seven patients exhibited a complete or partial objective response (CR/PR, 9.0%), 116 had stable disease (SD, 28.2%), 99 had progressive disease (PD,24%) and 160 (38.8%) did not have a post-baseline objective assessment. Partial responders demonstrated longer median OS (29.0 months) than patients with SD (22.1 months), or those with PD (10.8 months) or those who were not assessed (12.7 months). These results remained after landmark analysis. We found a significant association between ≥30% PSA declines and radiologic response, with ≥30% PSA declines occurring in all patients with CR/PR, 79.8% of patients with SD and 34.4% with PD. Radiologic response remained a significant but modest post-treatment prognostic factor for OS after adjusting for treatment, pain-response and ≥30% PSA-decline (p=0.009). Conclusions: In men with metastatic CRPC and measurable disease receiving chemotherapy, objective tumor response was prognostic for OS, and appears to complement PSA assessment. [Table: see text]

Pre-treatment neutrophil to lymphocyte ratio (NLR) association with curative intent metastasectomy (MSX) in metastatic renal cell carcinoma (RCC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16051-e16051
Author(s):  
Aline Fusco Fares ◽  
Daniel Vilarim Araujo ◽  
Eliza Dalsasso Ricardo ◽  
Marcelo Corassa ◽  
Maria Nirvana Cruz Formiga ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Regression Tree ◽  
Positive Association ◽  
Cox Proportional Hazards ◽  
Curative Intent ◽  
Risk Of Death ◽  
Metastatic Rcc

e16051 Background: NLR is a marker of inflammation and when elevated is associated with poor outcome in many tumors, including RCC. Hereby we evaluate the association of NLR with the likelihood of curative intent MSX. Methods: We retrospectively studied 846 patients diagnosed with metastatic RCC between 2007 and 2016. 116 patients fulfilled inclusion criteria: previous nephrectomy, no sarcomatoid features and available tumor specimens from metastatic site. Regression tree for censored data method was used to find the best NLR cut-off value. NLR was examined baseline – prior to MSX or targeted therapy. Chi-square test was used to evaluate associations between variables. We estimated overall survival (OS) using Kaplan-Meier curves. Cox proportional hazards regression models were fitted to evaluate the prognostic significance of NLR in univariable and multivariable analysis. Results: The median OS for the whole cohort was 45 months (95% CI, 27.6 to 62.4 months), and the median follow-up was 78.2 months. The best cut-off NLR value was 4.07. Higher NLR was associated with shorter OS when compared to the lower NLR cohort (11.5 months vs 68.3 months HR = 0.26, 95% CI: 0.15 – 0.97, p ≤ 0.0001, respectively). Univariate analysis revealed that bone metastasis and poor IMDC criteria were associated with worse OS and that MSX and lower NLR were associated with better OS. On multivariate analysis MSX, lower NLR and favourable/intermediate group on IMDC criteria were associated with a decreased risk of death (HR = 0.41, 95% CI 0.19-0.85, p = 0.018 and HR = 0.45, 95% CI 0.22-0.90, p = 0.025, HR = 0.35, 95% CI 0.16-0.79, p = 0.012, respectively). We found a positive association of lower NLR and curative intent MSX (p = 0.002). Conclusions: NLR is a prognostic marker in metastatic RCC and a ratio ≤ 4,07 is associated with a higher likelihood of curative intent MSX.

Serum insulin to predict time to castration-resistant progression and overall survival in metastatic androgen-dependent prostate cancer (mADPCa).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16038-e16038
Author(s):  
Farshid Dayyani ◽  
Graciela M. Nogueras-Gonzalez ◽  
Rebecca Slack ◽  
Randall E. Millikan ◽  
Amado J. Zurita ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Cancer Progression ◽  
Proportional Hazards ◽  
Serum Insulin ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Insulin Levels ◽  
Castration Resistant

e16038 Background: Duration of response to androgen-deprivation therapy (ADT) is highly variable in patients with mADPC and prognostic markers are needed. Insulin resistance and hyperinsulinemia may contribute to prostate cancer progression. We hypothesized that pretreatment serum insulin levels would predict time to castration-resistant progression (PFS) and overall survival (OS). Methods: Sera from men treated on a randomized phase 3 trial of first line ADT vs. ADT plus chemotherapy were retrospectively analyzed using a multiplex ELISA for cytokines and angiogenic factors (CAFs). Univariate and multivariate Cox proportional hazards regression models were used to identify associations between CAFs and PFS/OS. Results: 66 pts were evaluable, 86% Caucasian, median age 72 yrs, median PSA 31.5ng/mL, 77% Gleason score of ≥8, and 53% high volume metastatic disease (HVM). Thirty-five pts received ADT; 31 pts received ADT+chemo. In univariate analysis, higher pretreatment insulin and C-peptide were positively correlated with PFS, whereas higher hepatocyte-growth factor (HGF), osteopontin (OPN) and HVM were negatively correlated with PFS. In multivariate analysis, only higher insulin was associated with longer PFS (HR=0.72, 95%CI 1.32 -0.87; p<0.001), whereas higher HGF and OPN were associated with reduced PFS (HR=1.82, 95%CI 0.59-2.83, p<0.01 and HR=1.81, 95%CI 1.18-2.47, p<0.001, respectively). Higher Insulin and Program Death 1 (PD1) were associated with longer OS on multivariate analysis (HR=0.78 p<0.02 and HR=0.55 p<0.02, respectively), whereas HVM and higher OPN were associated with reduced OS (HR=2.28 p<0.01 and HR=1.60 p<0.02). Using low insulin, high HGF and high OPN as 3 independent risk factors (RF), 3 distinct risk groups could predict PFS: good (zero RF), intermediate (1 or 2 RF) and poor risk (3 RF), with median PFS of 6.90, 1.97, and 0.86 years, respectively (p<0.001). Conclusions: Higher pretreatment insulin was associated with prolonged PFS and OS in men with mADPC treated with ADT. Our data suggest that insulin levels are a biomarker for sensitivity to ADT and highlight the complex interactions between metabolism and PCa progression.

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