PSA levels after dexamethasone withdrawal (DW) in castration resistant prostate cancer (CRPC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 278-278
Author(s):  
Zafeiris Zafeiriou ◽  
Diletta Bianchini ◽  
Pasquale Rescigno ◽  
Michael Kolinsky ◽  
Joaquin Mateo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Response Duration ◽  
Castration Resistant Prostate Cancer ◽  
Chi Square ◽  
Number Of Patients ◽  
Patient Reported ◽  
Chi Square Test ◽  
Psa Response ◽  
Psa Progression ◽  
Group 2

278 Background: PSA decline (PSAD) in CRPC after withdrawal of antiandrogens and steroid related drugs is well established. DW responses have been anecdotal and not well characterized. In this study we investigated the frequency and magnitude of PSA changes after DW. Methods: We retrospectively identified patients treated in the Royal Marsden for CRPC with D monotherapy. Patients were considered evaluable if they had between DW and their next treatment or radiotherapy an interval of at least 7 days, no other intervention and at least one PSA reading. Patients who received radiotherapy during treatment with D or received D for palliation of symptoms were excluded. The number of patients showing PSAD was recorded together with its percentage change from baseline. Chi-square test was used to compare response rates between different groups and 95% confidence intervals (CI) for the description of frequencies. PSA progression (PSAP) was defined according to Prostate Cancer Working Group 2 criteria. Results: 200 patients were identified who had received D of which 50 were evaluable. During D treatment PSA responses were not available for 5 patients, while 16 (35%, 95%CI [20%-50%]) had a ≥ 50% PSAD which was confirmed a month later with a second reading. For the responders, the median duration of PSA response from initiation of treatment to PSAP was 293 days (range: 219 to 1063). After DW, PSAD was observed in 12 patients (24%, 95% CI [12%,36%]). PSAD ≥ 25%, ≥ 30% and ≥ 50% was observed in 6, 3 and 2 patients respectively (12%, 6% and 4%) and in only one could the ≥ 30% PSAD be confirmed with a second reading a month later. In 5 cases of ≥ 25% PSAD, next treatment was initiated despite a dropping PSA, after 8 to 43 days. In one case only was PSAP reached during DW with a response duration of 53 days from DW to PSAP. The frequency of ≥ 25% PSAW responses was not significantly different between patients with and without prior response to dexamethasone: 6% and 17% respectively, Chi-square test p = 0.29. One patient reported improvement of his urinary symptoms after DW. Conclusions: DW responses are observed in a minority of patients. This phenomenon merits further prospective characterization and needs to be considered in the design of clinical trials.

Efficacy of abiraterone and enzalutamide in patients who had disease progression within twelve months of completing docetaxel for metastatic castration sensitive prostate cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 241-241
Author(s):  
Gang Chen ◽  
David James VanderWeele ◽  
Fatima Karzai ◽  
Marijo Bilusic ◽  
Munjid Al Harthy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Specific Antigen ◽  
Response Duration ◽  
Optimal Timing ◽  
Castration Resistant Prostate Cancer ◽  
Duration Of Treatment ◽  
Psa Response ◽  
Psa Progression ◽  
Low Volume

241 Background: Docetaxel is a standard of care for mCSPC. Enzalutamide and abiraterone have been proven to improve survival in metastatic castration-resistant prostate cancer (mCRPC) patients. Little is known about patients who have been treated with docetaxel for mCSPC and subsequent therapeutic responses. This retrospective analysis is to evaluate the response duration of abiraterone and enzalutamide in patients who previously received docetaxel for mCSPC but developed mCRPC within 12 months. Methods: Clinical Trial NCT02649855 enrolled patients with newly diagnosed mCSPC who were treated with standard androgen deprivation therapy (ADT) and docetaxel (75 mg/m2 every 3 weeks for 6 cycles) sequenced with immunotherapy (PROSTVAC) from February 2016 to present. Patients who had progression (based on consecutive PSA rises or imaging) within 1 year of completing docetaxel and went on to subsequent abiraterone/enzalutamide were evaluated. (Note these are different PSA progression criteria than used in CHAARTED, Sweeney, NEJM, 2015). Results: Of the 46 patients evaluated regardless of immunotherapy sequence, 15 (33%) went on subsequent therapy after progression on docetaxel for mCSPC, with 12 patients starting abiraterone/enzalutamide (6 each with high and low volume disease). The median age was 62 (41-83) years. 7/12 patients (58.3%) initiated enzalutamide and 5/12 patients (41.7%) initiated abiraterone. The median duration of treatment for both was 7.12 (1.53–16.0) months, the median time to prostate-specific antigen (PSA) progression was 5.54 (0–15.83) months; 5/12 (41.7%) of patients did not have PSA response. Of note, patients with low volume disease had a median treatment duration of 5.88 months, 3 of them did not have PSA response. Conclusions: These data from a small cohort suggest that patients who have progression within 12 months of completing docetaxel for mCSPC have limited subsequent benefit from enzalutamide or abiraterone. Additional studies are required to determine optimal timing and treatment sequence for patients with mCSPC who rapidly develop mCRPC. Clinical trial information: NCT02649855.

Activity of gemcitabine-oxalipaltin (GemOx) plus prednisolone in patients with castration-resistant prostate cancer (CRPC) for whom docetaxel-based chemotherapy failed.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 108-108
Author(s):  
Jae-Lyun Lee ◽  
Yesul Kim ◽  
Jin-Hee Ahn ◽  
MeeKyung Choi ◽  
Seung-Woo Hong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Synergistic Effects ◽  
Drug Effects ◽  
Fixed Dose ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression ◽  
Grade 3

108 Background: We assessed the cytotoxic effects of the gemcitabine in combination with oxaliplatin (GemOx) in prostate cancer cell lines and evaluated the efficacy and safety of GemOx in patients with metastatic castration-resistant prostate cancer (CRPC) who failed docetaxel based chemotherapy. Methods: Gemcitabine and oxaliplatin were preclinically tested for their cytotoxic activity in LNCaP, PC3 and DU145 cell lines. The combined drug effects were evaluated using the Chou and Taladay analysis. Clinically, patients with CRPC who failed prior docetaxel chemotherapy were treated with gemcitabine 1,000 mg/m2 at fixed-dose rate (10 mg/m2/min) and oxaliplatin 100 mg/m2 intravenously every 2 weeks and prednisolone 5 mg orally twice daily. Unless disease progression or intolerability develops, treatment could be continued until 12 cycles. Primary endpoint was PSA response rate (PCWG 1.0 criteria). Results: The IC50of gemcitabine and oxaliplatin were, respectively, 1.25 μM and 0.69 μM for LNCaP cells; 50.00+ μM and 12.81 μM for PC3 cells; and 11.23 μM and 11.04 μM for DU145 cells. The GemOx combination displayed synergistic effects in all 3 cell lines. In phase II study, 31 patients were accrued. At the time of this analysis 7 patients were still continuing treatment. The median age was 67 years (range 57 ~ 81) and the median dose of docetaxel exposure was 525 mg/m2. A total of 231 cycles administered with a median of 9 cycles per patient. PSA responses were observed in 52% (95% CI, 34~69) and partial responses were observed in 7 of 10 patients with measurable disease. Out of 23 patients, 10 patients achieved pain response (44%). With a median FU duration of 8.0 months, the median time to PSA progression was 6.4 months (95% CI, 3.5~9.2). Peripheral neuropathy developed in 78% of patients but remained of grade 1 ~2 intensities. Frequently observed grade 3 or 4 toxicities were neutropenia (10%), thrombocytopenia (10%), anemia (3%), and diarrhea (3%). Conclusions: GemOx is active and well tolerated in patients with CPRC after docetaxel failure and deserves further investigation in this setting (NCT 01487720). Clinical trial information: NCT01487720.

Niclosamide in combination with abiraterone and prednisone in men with castration-resistant prostate cancer (CRPC): initial results from a phase Ib/II trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 192-192 ◽  
Author(s):  
Chong-xian Pan ◽  
Primo Lara ◽  
Christopher P. Evans ◽  
Mamta Parikh ◽  
Marc Dall'era ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Serum Testosterone ◽  
Castration Resistant Prostate Cancer ◽  
Phase Ib ◽  
Serum Trough ◽  
Psa Response ◽  
Group 2 ◽  
Recommended Phase Ii Dose ◽  
Initial Results

192 Background: Prostate cancer is driven by androgen receptor (AR) signaling. The variant AR-V7 lacks the ligand binding domain, constitutively activates the AR pathway, and confers resistance to Abiraterone (Abi) and enzalutamide (Enza). We discovered that the anti-helminthic drug niclosamide targets AR-V7 and sensitizes resistant CRPC to Enza and Abi. We hypothesize that niclosamide/PDMX1001 potentiates the efficacy of Abi against CRPC. Here we report the initial results of this ongoing investigator-initiated phase Ib/II trial. Methods: Eligible patients (pts) have progressive CRPC with serum testosterone < 50 ng/dl. No prior Abi was allowed. In the Phase Ib cohort, pts received Abi 1000 mg PO qd, prednisone 5 mg PO bid, with intrapatient dose-escalation of niclosamide/PDMX1001 from 400 mg PO bid to 1600 mg PO tid. Trough niclosamide/PDMX1001 levels were measured. The Phase II cohort will enroll 27 patients with detectable AR-V7 in the peripheral blood. Co-primary endpoints include toxicity and response as determined by the Prostate Cancer Working Group 2 criteria. Results: Of 6 pts (age 74-83) in the Phase Ib cohort, five pts tolerated a niclosamide/PDMX1001 dose of 1,600 mg po tid without dose limiting toxicity; per protocol, this is the recommended Phase II dose. Niclosamide/PDMX1001 trough level was 0.305 and 0.496 µM in the two pts analyzed thus far, higher than the target level of 0.1µM required for anti-cancer activity. Of 6 pts, two pts achieved complete PSA response ( < 0.01 ng/ml), compared to historical control 0/30 pts treated with Abi alone; two with partial PSA response (≥50% decrease). Of the remaining two pts, one was prematurely taken off from the study after one cycle because of rising PSA, and the other had PSA decrease of 17.1%, but biopsy of the only enlarged lymph node showed all necrotic tissue. The only toxicity was Grade 1 nausea and diarrhea. The Phase II cohort will now enroll. Molecular correlative studies will be presented. Conclusions: The combination of niclosamide/PDMX1001, Abi and prednisone is well tolerated with promising safety and efficacy data. Targeted serum trough levels of niclosamide are clinically achievable. Clinical trial information: NCT02807805.

Abiraterone acetate plus prednisone (AA+P) without continuing LHRH-therapy in patients with metastatic chemotherapy: Naive castrations-resistant prostate cancer—Results from the SPARE-trial (NCT02077634).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5046-5046 ◽  
Author(s):  
Carsten Henning Ohlmann ◽  
Christoph Ruessel ◽  
Roger Zillmann ◽  
Eva Hellmis ◽  
Henrik Suttmann ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Objective Response ◽  
Serum Testosterone ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Testosterone Levels ◽  
Psa Response ◽  
Secondary Endpoints ◽  
Psa Progression ◽  
Lhrh Therapy

5046 Background: The value of continuation of androgen deprivation therapy (ADT) in metastatic castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase/C17,20 lyase (Cyp17)-inhibitor, abiraterone acetate (AA), which in combination with prednisone (P), has the ability to further suppress serum testosterone levels over ADT alone, continuation of ADT seems to be negligible. Methods: The exploratory phase II trial randomized CRPC patients to receive continued ADT plus AA+P versus AA+P alone (NCT02077634), funded by Jansen-Cilag GmbH, Germany. The primary endpoint was rate of rPFS at month 12, not powered for a direct comparison between treatment arms. Secondary endpoints included PSA response rate, objective response, time to PSA progression and safety. Results: Altogether, 67 patients were randomized between 08/2014 to 04/2017. Median testosterone-levels (T) remained far below castrate-levels throughout treatment in all patients. However, in 6 patients (18%) from Arm B, T-levels increased above castrate levels within 28 days after cessation of AA+P treatment. Median treatment duration is shorter in Arm A. Safety analysis is underway and results will be presented. Conclusions: Results of this exploratory study suggest that treatment with AA+P without ADT may be effective in patients with mCRPC and that ADT may not be necessary in patients receiving AA+P. In some patients, serum-testosterone levels may rise rapidly upon treatment discontinuation so that the levels should be monitored closely. Clinical trial information: NCT02077634. [Table: see text]

Clinical activity of abiraterone acetate in patients with castration-resistant prostate cancer who received prior ketoconazole therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Bo Zhao ◽  
Jorge A. Garcia ◽  
Timothy D. Gilligan ◽  
Brian I. Rini ◽  
Robert Dreicer
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Underlying Mechanism ◽  
Abiraterone Acetate ◽  
Clinical Activity ◽  
Drug Discontinuation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression

99 Background: Studies have shown activity of Abiraterone acetate (AA) in patients (pts) with castration-resistant prostate cancer (CRPC) who have received prior ketoconazole. Prostate-specific antigen (PSA) response to AA in relation to previous PSA response to ketoconazole was investigated. Methods: A retrospective analysis was conducted to determine the clinical activity of AA in men with CRPC who have received prior ketoconazole therapy at our institution. Time to PSA progression (PSA TTP) was defined by PCWG2 criteria, a PSA reduction of 50% or more was considered as PSA response. Results: Thirty four pts were identified. Nineteen pts (56%) had previous PSA responses on ketoconazole, with a median PSA TTP of 11 months (95% confidence interval [CI] 6.8-19.9). Subsequently, 11 of 34 (33%) of pts achieved a PSA response on AA, with a median PSA TTP of 6 months (95% CI 4.9-9.5). Among the 19 pts having a PSA response on ketoconazole, only four (21%) pts subsequently had PSA response to AA. Two of these pts had transient PSA response with PSA TTP less than 3 months on kKetoconazole, one patient discontinued Ketoconazole due to side effects, one patient had intermittent non-castrate testosterone levels. In contrast, 7 of 15 (46.7%) pts without prior PSA response to ketoconazole subsequently achieved PSA response on AA (p=0.11). Of note, PSA reduction of less than 50% on AA was observed in 9 of 34 pts (26%), which was associated with a longer median PSA TTP compared to pts who had PSA-progressive disease (5.9 months [95% CI 3.5-7.3] vs.1.5 months [95% CI 1.0-3.5], p=0.028). Five of these nine patients had a prior PSA response to ketoconazole but required drug discontinuation for reasons other than disease progression. Conclusions: PSA response to prior ketoconazole therapy is associated with lower PSA response rate to subsequent AA. The observation suggests that there is a biologically distinct subset of patients who are ketoconazole-resistant but abiraterone-sensitive, the underlying mechanism needs to be further investigated.

Randomized phase II trial of docetaxel plus prednisolone with or without androgen deprivation treatment in castration-resistant prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 217-217
Author(s):  
Jae Ho Jeong ◽  
Hyejung Hyun ◽  
In Gab Jeong ◽  
Jun Hyuk Hong ◽  
Hanjong Ahn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Clinical Outcomes ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Randomized Phase Ii ◽  
Psa Response ◽  
Psa Progression ◽  
The Impact ◽  
Clinical Trial Information

217 Background: Androgen deprivation therapy (ADT) has been the main treatment option for patients with locally advanced or metastatic prostate carcinoma. However, the impact of continued ADT on clinical outcomes in castration-resistant prostate cancer (CRPC) patients treated with cytotoxic chemotherapy is controversial. We conducted a randomized phase II study to assess the impact of continued ADT in patients with CRPC receiving docetaxel plus prednisolone chemotherapy. Methods: Patients with CRPC were randomly assigned (in a 1:1 ratio) to receive docetaxel (75mg/m2 every 3 weeks) plus prednisolone (5mg twice daily on days 1-21) with ADT (leuprolide 11.25 mg long-acting depo every 12 weeks, ADT group) and docetaxel plus prednisolone without ADT (No-ADT group). For patients in the No-ADT group, ADT was resumed at the end of chemotherapy. The primary endpoint was time to PSA progression. Secondary objectives included PSA response rates, progression-free survival (PFS), and overall survival (OS). Suspension of leuprolide support prevented the attainment of our original goal of enrolling 80 men. Results: Between April 2011 and July 2014, 45 patients were enrolled in this study; 23 patients were randomly assigned to the ADT group and 22 to the No-ADT group. The median age was 68 years (range = 49-81) and median baseline serum PSA was 60.3 ng/mL (interquartile range = 14.7-157.3). Time to PSA progression was 6.5 months in ADT group and 4.3 months in No-ADT group, respectively (P = 0.673). PSA response rates were 55.2% and 44.8% in the ADT group and the No-ADT group, respectively (P = 0.463). The median PFS and OS were 5.3 months and 19.4 months for ADT patients and 4.3 months and 20.8 months for No-ADT patients, respectively (P = 0.608, P = 0.635). The testosterone level rose to more than the castrate level in 5 (22.7%) patients of the No-ADT group. Conclusions: Clinical outcomes were not significantly different when patients with CRPC received concurrent ADT, or were not so treated, when receiving docetaxel plus prednisolone chemotherapy. Clinical trial information: NCT01487902 Clinical trial information: NCT01487902.

scholarly journals Utility of prophylactic antibiotics for preventing febrile neutropenia during cabazitaxel therapy for castration-resistant prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Keitaro Watanabe ◽  
Takeo Kosaka ◽  
Hiroshi Hongo ◽  
Mototsugu Oya
Keyword(s):  
Prostate Cancer ◽  
Febrile Neutropenia ◽  
Prophylactic Antibiotics ◽  
University Hospital ◽  
Negative Group ◽  
Castration Resistant Prostate Cancer ◽  
Chi Square ◽  
Positive Group ◽  
Castration Resistant ◽  
Chi Square Test

AbstractThe aim was to investigate the efficacy of prophylactic antibiotics for the prevention of febrile neutropenia (FN) during cabazitaxel therapy for castration-resistant prostate cancer (CRPC) with G-CSF. We retrospectively studied 443 cycles of cabazitaxel therapy given to 56 patients with CRPC at Keio University Hospital between May 2012 and August 2018. Statistical analysis was conducted to determine whether the combination of prophylactic G-CSF and antibiotics was more effective in preventing FN, compared with prophylactic G-CSF alone. Prophylactic PEG-G-CSF or G-CSF was administered in all 443 cycles. Only fluoroquinolones were used as prophylactic antibiotics and were administered in 328 cycles (74.0%). FN occurred in 5 cycles (1.1%). Prophylactic antibiotics were administered in 327 cycles (74.6%) in the FN-negative group and in only 1 cycle (20.0%) in the FN-positive group. Chi-square test indicated the incidence of FN was significantly lower in the group that received prophylactic antibiotics compared with the group that did not receive prophylactic antibiotics (P = 0.017). Compared with prophylactic G-CSF alone, prophylactic G-CSF and antibiotics significantly suppressed the occurrence of FN.

Comparative effective analysis between enzalutamide and abiraterone in the treatment of metastatic castration-resistant prostate cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 217-217
Author(s):  
Akhil Chopra ◽  
Benjamin Haaland ◽  
Gilberto Lopes
Keyword(s):  
Prostate Cancer ◽  
Comparative Effectiveness ◽  
Phase Iii ◽  
P Value ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Effectiveness Analysis ◽  
Psa Response ◽  
Psa Progression ◽  
Comparative Effectiveness Analysis

217 Background: Recently Abiraterone (A) and Enzalutamide (E), new drugs with different novel mechanisms of action, have been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC) based on the COU-AA-301 and AFFIRM phase III trials, after docetaxel failure. The lack of direct comparative trials has introduced a new treatment dilemma for the practicing oncologist: is one drug more effective than the other? Methods: We performed an indirect comparative effectiveness analysis between E and A using the results of the AFFIRM and COU-AA-301 pivotal trials. Due to the lack of study-to-study replication of comparisons, these indirect comparisons are subject to the assumption that the relative effects of each drug relative to placebo are the same across studies. Results: 1) Overall survival (OS)- the respective hazard ratios (95% confidence intervals {CI}) in the AFFIRM and COU-AA-301 trials for OS for E vs. placebo and A vs. placebo were 0.63 (0.53-0.75) and 0.66 (0.56-0.79). The indirect estimate of the hazard ratio (HR) (95% CI; p-value) for E vs. A was 0.96 (0.75-1.22; 0.72) 2) Time to PSA progression- the respective HR(95% CI) in the AFFIRM and COU-AA-301 trials for time to PSA progression for E vs. placebo and A vs. placebo were 0.25 (0.20-0.30) and 0.58 (0.46-0.73). The indirect estimate of the HR (95% CI; p-value) for E vs. A was 0.43 (0.32-0.58; 4.3 × 10-8). 3) Radiographic progression Free Survival (rPFS)- The respective HR (95% CI) in the AFFIRM and COU-AA-301 trials for time to PSA progression for E vs. placebo and A vs. placebo were 0.40 (0.35-0.47) and 0.67 (0.59-0.78). The indirect estimate of the HR (95% CI; p-value) for E vs. A was 0.60 (0.49-0.74; 7.1 × 10-7). 4) PSA response- the respective odds ratios (95% CI) in the AFFIRM and COU-AA-301 trials for time to PSA progression for E vs. placebo and A vs. placebo were 77.08 (34.02-174.70) and 5.49 (3.84-7.84). The indirect estimate of the odds ratio (95% CI; p-value) for E vs. A was 14.04 (5.75-34.28; 6.6 × 10-9). Conclusions: In this indirect comparative effectiveness analysis, E appears to be more effective than A in terms of time to PSA progression, rPFS and PSA response. OS was not different.

ARN-509 in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 7-7 ◽  
Author(s):  
Matthew Raymond Smith ◽  
Emmanuel S. Antonarakis ◽  
Charles J. Ryan ◽  
William R. Berry ◽  
Neal Shore ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Phase I ◽  
Phase Ii ◽  
Nuclear Translocation ◽  
Performance Status ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Psa Response ◽  
Psa Progression

7 Background: ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of the androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion of a multicenter Phase I/II study is evaluating the activity of ARN-509 in 3 distinct patient populations of men with CRPC (high risk non-metastatic CRPC, metastatic treatment-naïve CRPC, and progressive disease after abiraterone acetate). Preliminary results for the cohort of patients with high-risk non-metastatic CRPC are presented here. Methods: All patients had CRPC, no radiographic evidence of metastases (pelvic lymph nodes <3 cm below the iliac bifurcation were allowed), and high risk for disease progression based on PSA value ≥ 8 ng/mL within 3 months of enrollment and/or PSA doubling time ≤ 10 months. Patients received ARN-509 at the recommended Phase II dose of 240 mg/day, previously established in Phase I (Rathkopf et al, GU ASCO 2012). The primary endpoint was PSA response rate at 12 weeks according to the Prostate Cancer Working Group 2 Criteria. Secondary endpoints included safety, time to PSA progression and 1-year metastasis-free survival. PSA assessments were collected every 4 weeks and tumor scans were performed every 16 weeks. Results: Forty-seven patients were enrolled between November 2011 and May 2012. The median age was 71 years (range 51 to 88) and at baseline, patients presented with ECOG performance status 0 (77%), Gleason Score 8-10 (32%), and median PSA of 10.7 ng/mL. All patients received prior treatment with a LHRH analog with or without a first-generation anti-androgen. At a median treatment duration of 20 weeks, three patients discontinued the study. The most common treatment-related adverse events (AE) were fatigue (30%), diarrhea (28%), nausea (17%), rash (13%), and abdominal pain (11%). The incidence of Grade 3 AEs was 6.4%, and no seizures have been observed to date. The 12-week PSA response was 91% and the time to PSA progression has not been reached. Conclusions: In men with high-risk non-metastatic CRPC, ARN-509 is safe and well tolerated with promising preliminary activity based on high PSA response rates. Clinical trial information: NCT01171898.

scholarly journals Comparison of effectiveness and safety outcomes of abiraterone versus enzalutamide in patients with metastatic castration-resistant prostate cancer: a systematic review and meta-analysis

2020 ◽  
Vol 23 ◽  
pp. 451-461
Author(s):  
Xin Wang ◽  
Yang Hui ◽  
Shihui Wang ◽  
Xiaopeng Hu ◽  
Xiaojia Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Response Rate ◽  
Cognitive Impairments ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Number Of Patients ◽  
Significant Difference ◽  
Psa Response

Purpose: To compare the effectiveness and safety between abiraterone and enzalutamide in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: We systematically searched for relevant articles from PubMed, Cochrane, Embase from their inception through November 4, 2019. Available articles from conferences were searched. The endpoints were prostate-specific antigen (PSA) response, overall survival (OS), progression-free survival (PFS), number of patients with any adverse event (AE). Results: 15 cohort studies involving 3546 participants were included in this meta-analysis. Pooled result showed that PSA response rate in the enzalutamide group was significantly greater than that in the abiraterone group (867 patients, risk ratio (RR) 0.69, 95% confidence interval (CI) 0.61-0.79, p＜0.00001, I2=29%). There was no significant difference in the total incidence of AEs between two groups (730 patients, RR 0.42, 95% CI 0.14-1.31, p = 0.14, I2=84%). The common adverse events observed in the published articles were fatigue and perceived cognitive impairments. Patients who received enzalutamide had the higher risk to have the feeling of fatigue compared with abiraterone group (2555 patients, RR 0.45, 95% CI 0.24-0.85, p=0.01, I2=92%). And there was no statistical difference between two groups respect to the side effect of perceived cognitive impairments (1856 patients, RR 0.94, 95% CI 0.47-1.88, p=0.85, I2=15%). Conclusions: Our results demonstrated that enzalutamide was associated with higher PSA response rate compared to abiraterone in patients with mCRPC, and no significant difference was found between two groups in the overall AE. But enzalutamide use induced higher risk of the AE of fatigue.

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