A phase 2 study of abiraterone acetate in japanese men with metastatic castration-resistant prostate cancer who had received docetaxel-based chemotherapy (original) (raw)
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Japanese journal of clinical oncology, 2014
Abiraterone acetate has been approved in >70 countries for chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) with prednisolone (5 mg/twice daily) in chemotherapy-naïve Japanese patients with metastatic castration-resistant prostate cancer was evaluated. Men, ≥20 years, with prostate-specific antigen levels of ≥5 ng/ml and evidence of progression were enrolled in this Phase 2, multicenter, open-label study. Primary efficacy endpoint was proportion of patients achieving a prostate-specific antigen decline of ≥50% from baseline (prostate-specific antigen response) after 12 week of treatment. Secondary efficacy endpoints and safety were assessed. A confirmed prostate-specific antigen response was observed in 29/48 (60.4%) patients by week 12; lower limit of two-sided 90% confidence interval was >35% (threshold response rate), demonstrating efficacy of abiraterone acetate. Secondary efficacy ...
European Urology, 2016
Coadministration of docetaxel and abiraterone acetate plus prednisone (AA + P) may benefit patients with metastatic castration-resistant prostate cancer (mCRPC) because of complementary mechanisms of action. COU-AA-206 was a phase 1b study to determine the safe dose combination of docetaxel and AA + P in three cohorts of chemotherapy-naïve mCRPC patients. Twenty-two patients received escalating doses of docetaxel plus AA + P. The primary endpoint was the proportion of patients with a dose-limiting toxicity (DLT) between weeks 2 and 7. The recommended phase 2 dose (RP2D) was the highest safe combination of docetaxel plus AA + P. Prostate-specific antigen (PSA) changes and intensive pharmacokinetic parameters for each drug were evaluated. Docetaxel 75 mg/m 2 [ 9 _ T D $ D I F F ] + AA 1000 mg + P 10 mg was deemed the RP2D, with DLT in one of six patients. PSA declines from baseline of 50% and 90% were observed for 85.7% and 66.7% of patients, respectively. During median follow-up of 14.5 mo, eight patients had PSA progression and six had radiographic progression or died. Systemic exposure was comparable for docetaxel and abiraterone when given alone or in combination. Studies are ongoing to confirm the efficacy of potent androgen receptor-targeted therapy plus taxane in early mCRPC. Patient summary: The combination of hormonal therapy and chemotherapy may improve outcomes in men with metastatic prostate cancer. This study demonstrates the ability to combine the hormonal therapy agent abiraterone[ 1 1 _ T D $ D I F F ] acetate, plus prednisone, and the chemotherapy drug docetaxel with an acceptable side effect profile. A high rate of prostate-specific antigen decline was seen, but the study was small and additional research is needed before this becomes a standard approach.
European Urology, 2014
Background: Taxanes may partly mediate their effect in castration-resistant prostate cancer (CRPC) through disruption of androgen-receptor trafficking along microtubules. This raises the possibility of cross-resistance between androgen-directed agents and docetaxel. Objective: To evaluate docetaxel efficacy after abiraterone treatment in CRPC patients. Design, setting, and participants: This was a single-institution, retrospective analysis in CRPC patients (N = 119) who either received abiraterone before docetaxel (AD) (n = 24) or did not receive abiraterone before docetaxel (docetaxel-only; n = 95). Men initiated docetaxel between December 2007 (the date abiraterone was first used at our center) and May 2013. Outcome measurements and statistical analysis: The primary efficacy end points were prostate-specific antigen progression-free survival (PSA-PFS) and clinical/radiographic progression-free survival (PFS) on docetaxel. Differences between groups were assessed using univariate and multivariable analyses. Results and limitations: Men in the AD group had a significantly higher risk for progression than those in the docetaxel-only group. Median PSA-PFS was 4.1 mo in the AD group and 6.7 mo in the docetaxel-only group (p = 0.002). Median PFS was also shorter in the AD group (4.4 mo vs 7.6 mo; p = 0.003). In multivariable analysis, prior abiraterone treatment remained an independent predictor of shorter PSA-PFS (hazard ratio [HR]: 3.48; 95% confidence interval [CI], 1.36-8.94; p = 0.01) and PFS (HR: 3.62; 95% CI, 1.41-9.27; p = 0.008). PSA declines 50% were less frequent in the AD group (38% vs 63%; p = 0.02). The small size and retrospective nature of this study may have introduced bias. Conclusions: Men receiving abiraterone before docetaxel were more likely to progress on docetaxel and less likely to achieve a PSA response than abiraterone-naïve patients. Cross-resistance between abiraterone and docetaxel may explain these findings; however, larger, more definitive studies are still needed to confirm this. Patient summary: We examined the efficacy of docetaxel in castration-resistant prostate cancer patients who either did or did not receive prior abiraterone. We found that men receiving abiraterone before docetaxel were less likely to achieve a PSA response and were more likely to progress sooner on docetaxel than abiraterone-untreated patients. This may be due to cross-resistance.
Abiraterone in heavily pretreated patients with metastatic castrate-resistant prostate cancer
Anti-Cancer Drugs, 2014
The aim of this study was to evaluate the activity and tolerability of abiraterone acetate in patients with metastatic castrate-resistant prostate cancer treated previously with more than three lines of chemotherapy. Patients received 1 g of abiraterone acetate (administered as four 250 mg tablets) orally once daily with prednisone at a dose of 5 mg orally twice daily. The primary endpoint was prostate-specific antigen (PSA) response. From August 2011 to January 2013, 36 patients were enrolled. PSA response was observed in 22 patients (61.1%, 95% confidence interval: 0.41-0.81). The median time to PSA progression was 7.3 months and after a median follow-up of 10.1 months, all patients were alive. The treatment was generally well tolerated; side effects secondary to mineralocorticoid excess resulting from blockade of CYP17 were largely controlled with prednisone. Abiraterone acetate seems to be an effective and well-tolerated treatment option for patients with metastatic castrate-resistant prostate cancer irrespective of the number of chemotherapy lines administered previously. Anti-Cancer Drugs 25:472-477
The Oncologist, 2013
On September 5, 2011, abiraterone was approved in the European Union in combination with prednisone or prednisolone for the treatment of metastatic castration-resistant prostate cancer (CRPC) in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen. On December 18, 2012, the therapeutic indication was extended to include the use of abiraterone in combination with prednisone or prednisolone for the treatment of metastatic CRPC in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.Abirateroneisaselective,irreversibleinhibitorofcytochrome P450 17␣, an enzyme that is key in the production of androgens. Inhibition of androgen biosynthesis deprives prostate cancer cells from important signals for growth, even in cases of resistance to castration. At the time of European Union approval and in a phase III trial in CRPC patients who had failed at least one docetaxel-based chemotherapy regimen, median overall survival for patients treated with abiraterone was 14.8 months versus 10.9 months for those receiving placebo (hazard ratio, 0.65; 95% confidence interval 0.54-0.77; p Ͻ .0001). In a subsequent phase III trial in a similar but chemotherapy-naïve patient population, median radiographic progression-free survival was 16.5 months for patients in the abiraterone treatment arm versus 8.3 months for patients in the placebo arm (hazard ratio, 0.53; 95% confidence interval, 0.45-0.62; p Ͻ .0001). Abiraterone was most commonly associated with adverse reactions resulting from increased or excessive mineralocorticoid activity. These were generally manageable with basic medical interventions. The most common side effects (affecting more than 10% of patients) were urinary tract infection, hypokalemia, hypertension, and peripheral edema.
The Prostate, 2014
Questions about optimal sequencing of systemic therapy in metastatic castration-resistant prostate cancer (mCRPC) and whether cross-resistance occurs between different drugs remain largely unanswered. Previous studies have produced conflicting data on the activity of docetaxel in patients who did not attain a prostate-specific antigen (PSA) response to abiraterone acetate (abiraterone). We investigated whether the biochemical response to abiraterone is associated with efficacy of subsequent docetaxel therapy. mCRPC patients treated with docetaxel after abiraterone were retrospectively identified at three Canadian institutions. Patients who had also received docetaxel prior to abiraterone were termed "docetaxel-experienced," while those not treated with docetaxel prior to abiraterone were termed "docetaxel-naïve." Treatment outcomes on docetaxel were stratified by prior response to abiraterone and compared using χ(2) -square test for confirmed PSA response rate (≥...
2020
Supplemental material, Supplementary_material_3 for Effectiveness of abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer in a large prospective real-world cohort: the ABItude study by Giuseppe Procopio, Vincenzo Emanuele Chiuri, Monica Giordano, Giovanna Mantini, Roberto Maisano, Roberto Bordonaro, Nicola Calvani, Gaetano Facchini, Sabino De Placido, Mario Airoldi, Andrea Sbrana, Donatello Gasparro, Giuseppe Mario Ludovico, Pamela Guglielmini, Emanuele Naglieri, Daniele Fagnani, Massimo Aglietta, Luigi Schips, Patrizia Beccaglia, Alessandro Sciarra, Lorenzo Livi and Daniele Santini in Therapeutic Advances in Medical Oncology
BMC cancer, 2017
To evaluate the safety and efficacy of abiraterone acetate (AA) in the "real life" clinical practice for men with chemotherapy-naïve metastatic castration-resistant prostate. A consecutive series of patients with mCRPC in 9 Italian tertiary centres treated with AA was collected. Demographics, clinical parameters, treatment outcomes and toxicity were recorded. The Brief Pain Inventory scale Q3 was tracked and patient treatment satisfaction was evaluated. Survival curves were estimated by the method of Kaplan-Meier and Cox regression and compared by the log-rank test statistic. We included 145 patients (mean age 76.5y). All patients were on androgen deprivation therapy. Patients had prior radiotherapy, radical prostatectomy, both treatments or exclusive androgen deprivation therapy in 17%, 33%, 9% and 40%, respectively. 57% of the patients had a Gleason score higher more than 7 at diagnosis. 62% were asymptomatic patients. The median serum total PSA at AA start was 17 ng/mL ...
Real world evidence: Abiraterone use post-docetaxel in metastatic castrate-resistant prostate cancer
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2018
Objectives The COU-AA-301 trial demonstrated that in men with metastatic castrate-resistant prostate cancer using abiraterone post-docetaxel increased overall survival. This study aims to assess this conclusion in a real world context. Design Retrospective chart review of a provincial Pharmacy BDM Database (a pharmacy dispensing software) and a provincial Electronic Chart (ARIA). Dispensing data, information on the state of the disease before and after abiraterone use, and information regarding effects of abiraterone were gathered. Setting Cancer centers in Alberta, Canada. Patients Metastatic castrate-resistant prostate cancer (CRPC) patients on abiraterone outside of a clinical trial who have previously had docetaxel chemotherapy for CRPC between February 2012 and May 2014. Primary outcome Overall survival from the time of abiraterone initiation. Results Overall survival increase of 17 months was consistent with the survival increase of 14.8 months observed in the pivotal trial. C...