scholarly journals Abiraterone acetate and prednisone in the pre- and post-docetaxel setting for metastatic castration-resistant prostate cancer: a mono-institutional experience focused on cardiovascular events and their impact on clinical outcomes

2018 ◽  
Vol 10 ◽  
pp. 175883401774581 ◽  
Author(s):  
Alessia Cavo ◽  
Alessandra Rubagotti ◽  
Elisa Zanardi ◽  
Chiara Fabbroni ◽  
Linda Zinoli ◽  
...  
Keyword(s):  
Cardiovascular Events ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Cox Proportional Hazards ◽  
Fluid Retention ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Cardiac Disorders

Background: The aim of this work was to to evaluate the incidence and risk factors of adverse events (AEs), focusing on cardiovascular events (CVEs) and hypokalemia, in patients treated with abiraterone acetate (AA) and prednisone (PDN) outside clinical trials, and their association with survival outcomes. Methods: This was a retrospective cohort study of 105 patients treated from 2011 to 2016. Incidence of AEs was descriptively summarized in the whole cohort and by subgroup (pre- versus post-docetaxel). Multivariable Cox proportional hazards models assessed factors associated with progression-free survival (PFS) and overall survival (OS). Results: Overall, median PFS and OS were 14.9 and 24.6 months, respectively. Prostate-specific antigen (PSA) ⩾ 10 ng/ml ( p = 0.007), Gleason Score >7 ( p = 0.008), Eastern Cooperative Oncology Group (ECOG) performance status (PS)1–2 ( p = 0.002), duration of androgen deprivation therapy (ADT) ⩽ 43.2 months ( p = 0.01), and body mass index (BMI) > 25 ( p = 0.03) were associated with worse PFS; presence of pain ( p = 0.01), ECOG PS1–2 ( p = 0.004), duration of ADT ⩽ 43.2 ( p = 0.05), and BMI > 25 ( p = 0.042) were associated with worse OS. Incidence of CVEs was as follows: hypertension 17.1%, fluid retention 4.8%, cardiac disorders 8.6%. 16.2% of patients developed hypokalemia. Age ⩾ 75 years was associated with higher probability of cardiac disorders ( p = 0.001) and fluid retention ( p = 0.03). CVEs did not impact on PFS or OS. Hypokalemia was associated with better median OS ( p = 0.036). Similar associations were observed after stratification by subgroup. Conclusions: Median PFS and OS estimates and incidence of CVEs and hypokalemia in our series are consistent with those of pivotal trials of AA plus PDN, confirming the efficacy and safety of this regimen also in the real-world setting. Elderly patients have higher odds of developing/worsening CVEs. However, regardless of age, CVEs were not associated with worse outcomes. Treatment-related hypokalemia seemed to be associated with longer OS, albeit this finding needs confirmation within larger, prospective series.

scholarly journals Phase II Multicenter Study of Abiraterone Acetate Plus Prednisone Therapy in Patients With Docetaxel-Treated Castration-Resistant Prostate Cancer

2010 ◽  
Vol 28 (9) ◽  
pp. 1496-1501 ◽  
Author(s):  
Daniel C. Danila ◽  
Michael J. Morris ◽  
Johann S. de Bono ◽  
Charles J. Ryan ◽  
Samuel R. Denmeade ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Circulating Tumor Cell ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Castration Resistant

Purpose Persistence of ligand-mediated androgen receptor signaling has been documented in castration-resistant prostate cancers (CRPCs). Abiraterone acetate (AA) is a potent and selective inhibitor of CYP17, which is required for androgen biosynthesis in the testes, adrenal glands, and prostate tissue. This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy. Patients and Methods Fifty-eight men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received AA (1,000 mg daily) with prednisone (5 mg twice daily). Twenty-seven (47%) patients had received prior ketoconazole. The primary outcome was ≥ 50% prostate-specific antigen (PSA) decline, with objective response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and changes in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and circulating tumor cell (CTC) numbers. Safety was also evaluated. Results A ≥ 50% decline in PSA was confirmed in 22 (36%) patients, including 14 (45%) of 31 ketoconazole-naïve and seven (26%) of 27 ketoconazole-pretreated patients. Partial responses were seen in four (18%) of 22 patients with RECIST-evaluable target lesions. Improved ECOG PS was seen in 28% of patients. Median time to PSA progression was 169 days (95% CI, 82 to 200 days). CTC conversions with treatment from ≥ 5 to < 5 were noted in 10 (34%) of 29 patients. The majority of AA-related adverse events were grade 1 to 2, and no AA-related grade 4 events were seen. Conclusion AA plus prednisone was well tolerated, with encouraging antitumor activity in heavily pretreated CRPC patients. The incidence of mineralocorticoid-related toxicities (hypertension or hypokalemia) was reduced by adding low-dose prednisone. The combination of AA plus prednisone is recommended for phase III investigations.

scholarly journals A multicentre analysis of abiraterone acetate in Canadian patients with metastatic castration resistant prostate cancer

2014 ◽  
Vol 8 (9-10) ◽  
pp. 583 ◽  
Author(s):  
Ravinder Clayton ◽  
Jackson Wu ◽  
Daniel Y Heng ◽  
Scott A North ◽  
Urban Emmenegger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Castration Resistant ◽  
Study Results

Introducton: The COU-AA-301 trial showed that abiraterone acetate (abiraterone), an oral cytochrome p450 CYP17 inhibitor, improved survival for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel. To better understand the non-clinical trial experience with abiraterone, we undertook a multicentre retrospective analysis of Canadian mCRPC patients treated with abiraterone.Methods: Consecutive patients with mCRPC who received abiraterone post-docetaxel were identified using centralized pharmacy records. These patients came from 5 Canadian tertiary cancer centres. Patients who received abiraterone for approved indications were included. Demographics, prognostic factors, treatment outcomes and adverse events were abstracted.Results: We included 187 patients who initiated abiraterone between January 2011 and June 2012. The median age at diagnosis and abiraterone start was 65 and 73 years, respectively. Seventy-three (39%) patients had metastatic disease at diagnosis. The Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2 and 3 was noted in 17, 96, 39 and 8 patients, respectively. The median prostate-specific antigen (PSA) at abiraterone start was 132, with a median PSA doubling time of 2.8 months. The median follow-up of patients still on active follow-up was 13 months. The proportion of patients achieving a ≥50% PSA reduction was 64/177 (36%). PSA progression-free survival was 3.5 months (95% confidence interval [CI], 3.0, 4.0). Median overall survival from start of abiraterone was 11 months (95% CI, 8.0, 13) and 38 months (95% CI, 31, 41) from date of mCRPC. Anemia and fatigue were the most commonly reported adverse events.Conclusions: This study carries the inherent limitations of a retrospective chart review. The outcomes in this series of men treated with abiraterone in a non-trial setting were expected, considering previous clinical trials. Our results, therefore, support the generalizability of the COU-AA-301 study results.

Is the duration of castration resistance predictive for sequential treatment responses in the metastatic castration-resistant prostate cancer setting?

2020 ◽  
pp. 107815522095161
Author(s):  
Özgecan Dülgar ◽  
Deniz Tataroğlu Özyükseler ◽  
Mustafa Başak ◽  
Seval Ay ◽  
Deniz Tural ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Real World Data ◽  
Ecog Performance Status ◽  
Castration Resistant ◽  
One Year

Objective Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA). Material and Method We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT. Results Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis. Conclusion TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.

Durable radiologic and clinical disease stability beyond PSA progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4553-4553
Author(s):  
Diletta Bianchini ◽  
Shahneen Kaur Sandhu ◽  
Amy Mulick Cassidy ◽  
Andrea Zivi ◽  
Janusz Mezynski ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Clinical Disease ◽  
Castration Resistant Prostate Cancer ◽  
Clinical Progression ◽  
Ecog Performance Status ◽  
Conversion Rates ◽  
Psa Progression

4553 Background: AA, a potent oral CYP17A1 inhibitor is approved for treatment of mCRPC with a survival advantage of 4.9 months. In clinical practice, response evaluation remains challenging for pts with mCRPC. CTC conversion from CTC ≥ 5 to CTC < 5 with treatment predicts for improved overall survival in mCRPC. We hypothesized that pts continue to have durable disease stability beyond PSA progression on AA. Methods: Prostate Specific Antigen (PSA) responses, radiological responses and CTC conversion rates were retrospectively analysed in pts treated on AA at our institution. CTCs, PSA and imaging were obtained at predefined time points during these studies. Radiological and PSA progression were defined by standard Prostate Cancer Working Group Criteria II. Clinical progression consisted of worsening disease related pain, skeletal events or declining performance status.Pearson’s chi-squared test and the Kaplan-Meier method were used for this analysis. Results: 141 patients [ECOG Performance Status 0-2; Median Age: 69.7 (range 44.7-87.1); 85 post-docetaxel, 56 pre-docetaxel] received AA. The median duration of clinical and radiological stable disease (SD) was 16.8 months (n=55) and 5.6 months (n=75) in patients with a baseline CTCs count of ≤ 5 cells/7.5mls and ≥ 5 cells/7.5 mls respectively. In the 105 patients with documented PSA progression on AA there was a median 5.7-month delay in detecting radiological and/or clinical progression (95% CI: 4.2, 8.4; range 0.3, 35.6 months). Radiological and clinical SD of ≥ 1 year, ≥ 2 years and ≥ 3 years on AA was observed in 43/141 (30.5%), 21/141 (14.9%) and 12/141 (8.5%) respectively. Conclusions: Radiological and clinical disease stabilization beyond PSA progression is maintained in a high proportion of mCRPC patients treated with AA. Future studies should evaluate whether continued AA treatment beyond PSA and radiological progression can impact outcome.

scholarly journals A prognostic model for stratifying clinical outcomes in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate

2017 ◽  
Vol 12 (2) ◽  
pp. E47-52 ◽  
Author(s):  
Daniel Joseph Khalaf ◽  
Claudia M. Avilés ◽  
Arun A. Azad ◽  
Katherine Sunderland ◽  
Tilman Todenhöfer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Group Performance ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Prognostic Index ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Progression

Introduction: Recently, a prognostic index including six risk factors (RFs) (unfavourable Eastern Cooperative Oncology Group performance status [ECOG PS], presence of liver metastases, short response to luteinizing hormone-releasing hormone [LHRH] agonists/ antagonists, low albumin, increased alkaline phosphatase [ALP] and lactate dehydrogenase [LDH]) was developed from the COUAA- 301 trial in post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate. Our primary objective was to evaluate this model in a cohort of chemotherapy-naive mCRPC patients receiving abiraterone.Methods: We identified 197 chemotherapy-naive patients who received abiraterone at six BC Cancer Agency centres and who had complete information on all six RFs. Study endpoints were prostate-specific antigen (PSA) response rate (RR), time to PSA progression, time on treatment, and overall survival (OS). PSA RR and survival outcomes were compared using Χ2 test and log-rank test. Multivariable Cox proportional hazard analysis was performed to identify RFs independently associated with OS.Results: Patients were classified into good (0‒1 RFs), intermediate (2‒3 RFs), and poor (4‒6 RFs) prognostic groups (33%, 52%, and 15%, respectively). For good-, intermediate-, and poor-risk patients, PSA RR (≥50% decline) was 60% vs. 42% vs. 40% (p=0.05); median time to PSA progression was 7.3 vs. 5.3 vs. 5.0 months (p=0.02); and median OS was 29.4 vs. 13.8 vs. 8.7 months (p<0.0001).Conclusions: The six-factor prognostic index model stratifies clinical outcomes in chemotherapy-naive mCRPC patients treated with abiraterone. Identifying patients at risk of poor outcome is important for informing clinical practice and clinical trial design.

Response to cabazitaxel in CRPC patients previously treated with docetaxel and abiraterone acetate.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 155-155 ◽  
Author(s):  
Carmel Jo Pezaro ◽  
Sylvestre Le Moulec ◽  
Laurence Albiges ◽  
Aurelius Gabriel Omlin ◽  
Yohann Loriot ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Performance Status ◽  
Abiraterone Acetate ◽  
Cross Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Duration Of Treatment ◽  
Ecog Performance Status ◽  
Third Line ◽  
Line Setting ◽  
Taxane Chemotherapy

155 Background: Cabazitaxel, which is a tubulin-binding chemotherapy, and the CYP-17 androgen biosynthesis inhibitor abiraterone acetate (AA) are both approved for patients with metastatic castration resistant prostate cancer (CRPC) following docetaxel chemotherapy. Recent preclinical data suggest that taxanes impact AR signalling and could imply cross-resistance between new AR targeting treatments and taxane chemotherapy. The aim of this study is to evaluate the antitumor activity of cabazitaxel after AA. Methods: We retrospectively evaluated antitumor activity of cabazitaxel in patients (pts) with metastatic CRPC and progressive disease after docetaxel and AA. Radiological response by RECIST, PSA response by PCWG2 criteria and symptomatic benefit were examined. Results: 89 pts were treated with third-line cabazitaxel, after docetaxel (median 8 cycles; range: 4-12), and AA (median duration of treatment 4.8 months, range: 1-55 months). At cabazitaxel initiation median age was 68 years (range: 53-83), ECOG performance status was 0 or 1 in 70% of pts, and median PSA was 309 ng/ml (range: 3.75-9150). Bone, lymph node and visceral metastases were present in 80 pts (89%), 37 pts (41%), and 12 pts (13%) respectively. An average of 6 cycles of cabazitaxel (range 1-15) were administered. All pts had PSA data available and 44 (49%; 95% CI 39-60%) had a 50% or greater PSA decline. In the 35 pts with RECIST evaluable disease, 7 (20%; 95% CI 8-37%) had a partial response. Conclusions: In men with metastatic CRPC cabazitaxel appears to retain activity in the third-line setting following docetaxel and AA.

Clinical outcomes and safety in men ≥ 75 and < 75 years with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide in the phase 3 PREVAIL trial.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 200-200 ◽  
Author(s):  
Julie Nicole Graff ◽  
Giulia Baciarello ◽  
Andrew J. Armstrong ◽  
Celestia S. Higano ◽  
Peter Iversen ◽  
...  
Keyword(s):  
Performance Status ◽  
Specific Antigen ◽  
Age Groups ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Phase 3 ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Treatment Safety ◽  
The Impact

200 Background: In the phase 3 PREVAIL trial, enzalutamide (ENZA), an androgen receptor inhibitor, improved overall survival (OS) and radiographic progression-free survival (rPFS) relative to placebo (PBO) in chemotherapy-naïve men with mCRPC. Methods: PREVAIL randomized 1,717 patients (pts) with asymptomatic or minimally symptomatic chemotherapy-naïve mCRPC 1:1 to ENZA 160 mg daily or PBO. Coprimary endpoints were OS and rPFS. This prespecified analysis evaluated the impact of age (≥ 75 vs < 75 years) on efficacy and safety. Results: In PREVAIL, 609 (35%) pts were aged ≥ 75 years. This older subset had several poorer baseline prognostics relative to those aged < 75 years: worse ECOG performance status (ECOG 1: 45.0% vs 24.7%), higher prostate-specific antigen (PSA; 73.3 vs 37.3 ng/mL) and more cardiovascular disease (26.9% vs 16.5%). In both older and younger pts, ENZA improved OS, rPFS and time to PSA progression (Table). Pts aged ≥ 75 years in both the ENZA and PBO groups combined had a higher rate of grade ≥ 3 adverse events (46% vs 37% in younger pts) and among enzalutamide-treated men more older pts reported falls (any grade; ENZA 19% and PBO 8%) than younger pts (ENZA 7% and PBO 4%). Fewer pts ≥ 75 years received subsequent antineoplastic therapies. Conclusions: In PREVAIL, efficacy outcomes in elderly (≥ 75 years) and younger (< 75 years) pts with chemotherapy-naïve mCRPC were comparable and pts consistently benefited from ENZA treatment. Safety with ENZA was similar in both age groups, although older pts reported a higher incidence of falls and received fewer subsequent antineoplastic therapies. Clinical trial information: NCT01212991. [Table: see text]

Phase II multicenter study of chemotherapy (chemo)-naive castration-resistant prostate cancer (CRPC) not exposed to ketoconazole (keto), treated with abiraterone acetate (AA) plus prednisone

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5046-5046 ◽  
Author(s):  
C. Ryan ◽  
E. Efstathiou ◽  
M. Smith ◽  
M. Taplin ◽  
G. Bubley ◽  
...  
Keyword(s):  
Performance Status ◽  
Median Number ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Androgen Withdrawal ◽  
Psa Response ◽  
Grade 3 ◽  
Hormonal Therapies ◽  
Ecog Ps

5046 Background: AA is a potent inhibitor of the enzyme CYP17, a major contributor to androgen biosynthesis. Keto is also known to inhibit this enzyme but AA is many-fold stronger in its action. 33 pts with progressive metastatic disease, normal organ function, ECOG performance status (PS) 0–1, and no prior chemo were enrolled. Pts with prior keto treatment were excluded. AA (1000 mg qd) plus prednisone (5mg bid) were administered orally in 28 day cycles. Methods: Results: At baseline median age was 71.0 (range 52–85) yrs and median PSA was 24.7 (range 7.1–1110.0) ng/mL;19/26 pts (73%) had an ECOG PS of 0 and 7/26 (27%) had PS of 1; the median number of prior hormonal therapies was 2; all pts were on LHRHa and 73% of pts had received anti-androgen, all of whom had undergone prior anti-androgen withdrawal. Pts were evaluated at each cycle for PSA response according to PSAWG criteria. 27 pts have available data for PSA response. Total maximal PSA declines of ≥30%, ≥50%, ≥90% were observed in 89% (24/27), 85% (23/27) and 41% (11/27) pts, respectively. Week 12 PSA declines displayed a similar and sustained trend: ≥30%, ≥50% and ≥90% PSA decline in 82%, 78%, and 26% of pts. Post-treatment ECOG PS score was 0 in 24 (92%) pts: 19% experienced improvement in PS (PS 1 to 0 in 5 pts) and 19/19 pts maintained a PS of 0; Median time to PSA progression has not been reached. Majority of adverse events were grades 1–2. Incidence of hypokalemia - 12%; HTN - 6%; edema - 15%. One pt experienced a grade 3 drug-related HTN. Conclusions: Abiraterone acetate plus prednisone has significant anti-cancer activity in patients with metastatic CRPC not previously treated with ketoconazole or chemotherapy, as demonstrated by declines in PSA and improvement in performance status, and is well-tolerated. [Table: see text]

Safety of abiraterone acetate (AA) in castration-resistant prostate cancer (CRPC) patients with concomitant cardiovascular disease.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 168-168
Author(s):  
Giuseppe Procopio ◽  
Elena Verzoni ◽  
Isabella Testa ◽  
Davide Biasoni ◽  
Tullio Torelli ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Adverse Events ◽  
Safety Data ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Fluid Retention ◽  
Castration Resistant Prostate Cancer ◽  
Cardiac Disorders ◽  
Grade 3 ◽  
Dose Modifications

168 Background: Abiraterone acetate (AA) is an inhibitor of extragonadal androgen biosynthesis that prolongs overall survival in CRPC patients who have received a chemotherapy including docetaxel. The most common adverse events related to AA therapy were fluid retention, hypertension, hypokaliemia and cardiac disorders. No safety data are available in patients with concomitant cardiac disease. Methods: Metastatic CRPC patients were enrolled in this prospective study if they were also suffering from a concomitant controlled cardiovascular disease. AA 1000 mg per day and prednisone 5 mg bid were administered orally until grade 3-4 adverse events (AE) or disease progression. The primary endpoint was the safety profile while the secondary endpoints were progression-free survival and PSA response. Results: From April to September 2011, 33 CRPC patients with concomitant cardiovascular disorders have been treated with AA. Main patients characteristics were: median age 71 years (range 57–81); baseline mean PSA value 40 ng/ml (6.32-995); the most common sites of disease were bone (27 pts, 81%), lung (11 pts, 33%) and liver (5 pts, 15%). All patients were previously challenged with at least 2 lines of hormone therapy and 1 chemotherapy regimen including docetaxel. The most common pre-existing cardiac disorders were hypertension 22 (66%), arrhythmias 4 (12%), cardiac ischemia 3 (9%) and conduction irregularity 2 (4%). Additionally 9 patients (27%) had metabolic disorders including dislipidemy and hyperglicemia. AA was feasible without inducing grade 3-4 AE nor treatment modification. The most common grade 1-2 AE were asthenia (27%), hypertension (18%) and fluid retention (28%). After a median time of treatment of 4 months (range 2–7 months) no dose modifications due to toxicity were required. No efficacy data are still available. Conclusions: Treatment with AA was feasible and well tolerated also in patients suffering from cardiac comorbidities and risk factors for cardiovascular disease.

Pharmacokinetic food-effect study of abiraterone acetate (AA) in patients with metastatic castration resistant prostate cancer (mCRPC): The ABIFOOD trial (EudraCt number: 2012-003226-25).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 227-227 ◽  
Author(s):  
M. Espinosa ◽  
A Falcon ◽  
A Gutierrez-Valencia ◽  
A Cervera ◽  
CM Rosso-Fernandez ◽  
...  
Keyword(s):  
Food Effect ◽  
Performance Status ◽  
Progression Free Survival ◽  
Effect Study ◽  
Abiraterone Acetate ◽  
Fat Content ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Time Curve

227 Background: A.A has been approved for the treatment of mCRPC before and after docetaxel. The standard regime consists on daily A.A. 1.000 mg in a fasting state along with prednisone 10mg q.d. However, data from pharmacokinetic (PK) studies in patients (pts) and healthy volunteers has revealed a significant food-effect with up to 7-10 folder increase in area under plasma concentration-time curve (AUC) when A.A is given with food, specially with fat content, [Chi KN, J Clin Pharmacol 2015]. Methods: ABIFOOD is a phase I, randomized trial to evaluate the short and long-term effect of diet on the PKs of A.A. in pts with mCRPC who have progressed to docetaxel. Eligible pts include men ≥ 18 years old with mCRPC, ECOG performance status (PS) < 2 and an adequate organ function. Pts are randomly assigned to receive 4-weekly cycles of 250 mg A.A with standard meal (Arm A), 250 mg A.A with high-fat meal (Arm B) or 1000 mg A.A in fasting conditions (Arm C). PK analyses are conducted at week 1 (W1) and cycle 5. Results: Fifteen pts (5, 3 and 7 in arms A, B and C respectively) have been included and 6 are still on treatment. Median age is 72, 97% have ECOG-PS 1. Gleason Score is > 8 in 6 (40%) pts.Geometric mean abiraterone [AUC (ng.h/ml) (IQR)] at W1 did not significantly differ between treatment arms [arm A: 404.68 (368.4 - 488.2), arm B: 372 (334.6 - 440.5) arm C: 656.51 (387.8 – 1144.5) p 0.15]. PK data did not influence activity or toxicity. Progression free survival was 8.50, 6.33 and 4.86 months in Arms A, B and C respectively (p 0.53). One patient in arm A is still on treatment after 17 cycles. Conclusions: The administration of lower doses of A.A with food [regardless the fat content], might achieve comparable plasma levels to standard dosing with no detriment in efficacy or toxicity parameters. The study is actively recruiting and data on additional pts and long term PK parameters will be presented. Clinical trial information: EudraCt number: 2012-003226-25.

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