scholarly journals A prospective phase-II trial of biweekly docetaxel plus androgen deprivation therapy in patients with previously-untreated metastatic castration-naïve prostate cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Seonggyu Byeon ◽  
Hongsik Kim ◽  
Hwang Gyun Jeon ◽  
Seong Il Seo ◽  
Seong Soo Jeon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Androgen Deprivation Therapy ◽  
Phase Ii ◽  
Eastern Cooperative Oncology Group ◽  
Multivariable Analysis ◽  
Androgen Deprivation ◽  
Free Survival ◽  
Psa Response ◽  
Prospective Phase

Abstract Introduction The aim of this prospective phase II study was to evaluate the efficacy and safety of biweekly docetaxel plus androgen-deprivation therapy (ADT) in patients with metastatic castration-naïve prostate cancer (mCNPC). Patients and methods Patients with histologically-proven, previously-untreated mCNPC received ADT plus docetaxel, 40 mg/m2. Docetaxel was repeated every 2 weeks, up to 12 cycles. Endpoints included castration-resistant prostate cancer (CRPC)-free survival, prostate-specific antigen (PSA) response, and safety. Results A total of 42 patients were registered and analyzed for final outcomes. Of the 42 patients, 36 (86%) completed the 12 planned cycles of docetaxel plus ADT. During a median follow up of 25 months, all but two patients (95%) achieved a PSA response with a nadir PSA level of 0.42 ng/ml (range 0.01–1280.87). The median CRPC-free survival was 26.4 months (95% confidence interval [CI] 20.9–32.0) with a one-year CRPC-free rate of 79% (33 patients, 95% CI 66–91). Multivariable analysis revealed that the performance status of the Eastern Cooperative Oncology Group 0 was independently associated with longer CRPC-free survival (hazard ratio [HR] 0.27, 95% CI 0.07–0.99). The most common adverse events of any grade were anemia (95%), followed by nail changes (33%), fatigue (29%), and oral mucositis (26%). Severe (grade 3 or higher) adverse events were infrequent: pneumonitis (n = 2), diarrhea (n = 1), and neutropenia (n = 1). Conclusion Our results suggest that biweekly docetaxel plus ADT is feasible, and clinical efficacy does not seem to be compromised compared to a standard triweekly docetaxel 75 mg/m2 plus ADT regimen.

Phase II study of biweekly docetaxel plus androgen-deprivation therapy (ADT) in patients with previously-untreated, metastatic, prostatic adenocarcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17580-e17580
Author(s):  
Seonggyu Byeon ◽  
Hana Kim ◽  
Hongsik Kim ◽  
Hwang Gyun Jeon ◽  
Seong Soo Jeon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Phase Ii ◽  
Specific Antigen ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Free Survival ◽  
Psa Response ◽  
One Year

e17580 Background: To evaluate the efficacy and safety of biweekly docetaxel (bD) plus androgen-deprivation therapy (ADT) in metastatic castration-naïve prostate cancer (mCNPC). Methods: This was an open-label, prospective, single-arm phase II trial. 42 patients with mCNPC were treated with docetaxel 40 mg/m2 every two weeks plus ADT. The primary end point was one year castration-resistant prostate cancer (CRPC)-free survival rate and the secondary end points were prostate-specific antigen (PSA) response, time to CRPC and safety. Results: Most patients (87.5%) had Gleason score 8 or more. The median value of PSA at initial treatment was 66.9 ng/ml (range 0.04 to 2339). After bD plus ADT, 39 patients (92.9%) had a PSA response (reduced PSA level 50% or more). The time to CRPC (one-year CRPC free survival 73.6%) and the duration of PSA response (18 months response 80.4%) did not reach the median. The bD plus ADT regimen was well-tolerated. The most common adverse events included neutropenia, nail changes and diarrhea. Conclusions: bD plus ADT treatment demonstrated favorable treatment outcomes with tolerability. Clinical trial information: NCT03061643 .

Novel androgen receptor inhibitors in nonmetastatic castration-resistant prostate cancer: A network meta-analysis.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 131-131
Author(s):  
Amanda Elizabeth Hird ◽  
Diana E. Magee ◽  
Bimal Bhindi ◽  
Xiang Y. Ye ◽  
Thenappan Chandrasekar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Adverse Events ◽  
Androgen Deprivation Therapy ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival

131 Background: Novel non-steroidal anti-androgens (NSAAs) including enzalutamide, apalutamide, and darolutamide with androgen deprivation therapy (ADT) have proven efficacy in men with high-risk non-metastatic castrate resistant prostate cancer (nmCRPC). However, in the absence of direct comparative trials, there is little evidence to guide therapeutic choice. Our objective was to perform a network meta-analysis to compare agents and perform a class-level meta-analysis of NSAAs with androgen deprivation therapy (ADT) versus ADT-alone. Methods: We performed a systematic review of phase III parallel-group RCTs in men ≥18 years of age with nmCRPC using EMBASE and MEDLINE, indexed as of March 8, 2019. Our primary outcome was metastasis free survival (MFS). Secondary outcomes included OS, PSA progression free survival (PFS), and rates of grade 3-4 adverse events (AEs). Three RCTs were identified. We performed a random effects meta-analysis of NSAA versus ADT-alone using the inverse variance technique for meta-analysis for efficacy outcomes and the Mantel-Haenszel method for meta-analysis of dichotomous data for AEs. We then performed a network meta-analysis to compare outcomes between NSAAs using fixed-effect models in a Bayesian framework. We estimated the relative ranking of the different treatments for each outcome. Results: Pooled MFS, PSA-PFS, and OS were significantly greater with NSAA versus placebo (HR:0.32,95%CI:0.25-0.41, HR:0.08,95%CI:0.05-0.13, and HR:0.74,95%CI:0.61-0.90, respectively). Apalutamide and enzalutamide had a 56% and 44% likelihood of maximizing MFS, respectively. There was a 44%, 41%, and 15% likelihood that apalutamide, darolutamide and enzalutamide offered the greatest OS benefit, respectively. There was a 61% chance that darolutamide was preferred with respect to AEs. Conclusions: NSAAs improve survival outcomes in patients with high-risk nmCRPC. Apalutamide and enzalutamide may offer improved oncological outcomes. Darolutamide may result in fewer adverse events. These differences, if confirmed, would be meaningful to patients and practitioners when selecting treatment.

scholarly journals Next-generation androgen receptor inhibitors in non-metastatic castration-resistant prostate cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592097813
Author(s):  
Pernelle Lavaud ◽  
Clément Dumont ◽  
Constance Thibault ◽  
Laurence Albiges ◽  
Giulia Baciarello ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Androgen Receptor ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Next Generation ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Recent Advances

Until recently, continuing androgen deprivation therapy (ADT) and closely monitoring patients until evolution towards metastatic castration-resistant prostate cancer (CRPC) were recommended in men with non-metastatic CRPC (nmCRPC). Because delaying the development of metastases and symptoms in these patients is a major issue, several trials have investigated next-generation androgen receptor (AR) axis inhibitors such as apalutamide, darolutamide, and enzalutamide in this setting. This review summarizes the recent advances in the management of nmCRPC, highlighting the favourable impact of next-generation AR inhibitors on metastases-free survival, overall survival and other clinically meaningful endpoints.

scholarly journals Impact of Androgen Deprivation Therapy Associated to Conformal Radiotherapy in the Treatment of D’Amico Intermediate-/High-Risk Prostate Cancer in Older Patients

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 75
Author(s):  
Anne-Laure Couderc ◽  
Emanuel Nicolas ◽  
Romain Boissier ◽  
Mohammed Boucekine ◽  
Cyrille Bastide ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Androgen Deprivation Therapy ◽  
Older Patients ◽  
External Beam Radiotherapy ◽  
Total Duration ◽  
Androgen Deprivation ◽  
Free Survival ◽  
Cancer Group ◽  
Tertiary Center

Purpose/objective: The association of 3D Conformal External Beam Radiotherapy (3D-CEBRT) with adjuvant Androgen Deprivation Therapy (ADT) proved to treat patients with intermediate- and high-risk localized prostate cancer (IR and HR). However, older patients were underrepresented in literature. We aimed to report the oncological results and morbidity 3D-CEBRT +ADT in ≥80 years patients. Material and Methods: From June 1998 to July 2017, 101 patients ≥80 years were included in a tertiary center. The median age was 82 years. ADT was initiated 3 months prior 3D-CEBRT in all patients, with a total duration of 6 months for IR prostate cancer (group A; n = 41) and 15 months for HR prostate cancer (group B; n = 60). Endpoints included overall survival (OS), metastasis-free survival (DMFS), biochemical recurrence-free survival (BRFS) and toxicity. Results: Five years-OS was 95% and 86.7% in groups A and B, respectively. Cardiovascular events occurred in 22.8% of ≥80 years patients with no impact on OS. In the multivariate analysis, age <82 years, Karnofsky index and normalization of testosterone levels were significantly associated with better OS. Conclusion: Age ≥80 years should not be a limitation for the treatment of IR and HR prostate cancer patients with 3D-CEBRT and ADT, but cardiovascular monitoring and prevention are mandatory.

scholarly journals Stereotactic body radiotherapy versus conventional/moderate fractionated radiation therapy with androgen deprivation therapy for unfavorable risk prostate cancer

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Sagar A. Patel ◽  
Jeffrey M. Switchenko ◽  
Ben Fischer-Valuck ◽  
Chao Zhang ◽  
Brent S. Rose ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Stereotactic Body Radiotherapy ◽  
Multivariable Analysis ◽  
Androgen Deprivation ◽  
Sensitivity Analyses ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Risk Of Death ◽  
Risk Prostate Cancer

Abstract Background Ultrahypofractionation using stereotactic body radiotherapy (SBRT) is an increasingly utilized technique for men with prostate cancer (PC). The comparative efficacy of SBRT plus androgen deprivation therapy (ADT) compared to fractionated radiotherapy (EBRT) plus ADT in higher-risk prostate cancer is unknown. Methods Men > 40 years old with localized PC treated with external beam radiation and concomitant ADT for curative intent between 2004 and 2016 were analyzed from the National Cancer Database. Patients who lacked ADT or risk stratification data were excluded. 558 men treated with SBRT versus 40,797 men treated with conventional or moderately hypofractionated EBRT were included. Patients were stratified by unfavorable intermediate (UIR) and high (HR) risk using NCCN criteria. Kaplan Meier and Cox proportional hazards were used to compare overall survival (OS) between RT modality, adjusting for age, race, and comorbidity index. Results With a median follow up of 74 months, there was no difference in estimated 6-year OS between men treated with SBRT versus EBRT regardless of risk group. On multivariable analysis, there was no difference in risk of death for men treated with SBRT compared to EBRT (UIR: adjusted HR 1.09, 95% CI 0.68–1.74, p = .72; HR: adjusted HR 0.93, 95% CI 0.76–1.14, p = .51). On sensitivity analyses, when confining the cohort to men treated with NCCN-preferred dose fractionations, with no comorbidities, or < 65 years old, there remained no survival difference between treatment groups for both UIR and HR. Conclusion Within study limitations, we found no difference in survival between SBRT+ADT and standard of care EBRT+ADT for UIR or HR PC. These results support recent NCCN guideline updates, which include SBRT as a non-preferred option for higher risk men. Prospective validation would further strengthen the evidence basis behind these recommendations.

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