The use of intermittent enzalutamide dosing in the treatment of metastatic castrate-resistant prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 81-81
Author(s):  
Michael Rowe ◽  
Ayesha Hidayat ◽  
Stuart Walter ◽  
Adam Pollard ◽  
Timothy Norris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Time ◽  
Median Number ◽  
Significance Level ◽  
Kaplan Meier ◽  
Single Centre Study ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Continuous Scheduling

81 Background: Intermittent hormone manipulation in castrate-sensitive prostate cancer can improve quality of life whilst maintaining comparable disease outcomes with continuous scheduling. Enzalutamide is effective in metastatic castrate-resistant prostate cancer (mCRPC) treatment but can have significant side-effects. We conducted a retrospective analysis of patients treated with intermittent enzalutamide compared with continuous dosing. Methods: Patients prescribed enzalutamide for mCRPC at Royal Cornwall Hospital from September 2011 to February 2018 were included. Data was collected from electronic medical records, selecting patients with at least a 1 month treatment break. Kaplan-Meier analysis of overall survival from enzalutamide start (OS), time to PSA failure (TTF) and total enzalutamide treatment time (TTT) was calculated for intermittent and continuous responders (>50% PSA drop), assigned significance level of 0.05. Results: 243 patients received enzalutamide, 110 (45%) were continuous responders and 29 (12%) had intermittent dosing. All patients treated intermittently had a PSA response prior to first treatment break, which was most commonly for fatigue (60%). 25% were still receiving enzalutamide. Median number of breaks was 1 (range 1-7), time on treatment was 70% and time to first break was 5 months. The intermittent group had significantly improved OS with median not reached, median OS for continuous responders was 19 months (HR 2.39, 95% CI 1.53-3.76, p=0.002). The intermittent group had prolonged TTF (median 13 vs 6 months, p=0.001) and TTT (median 30 vs 10 months, p=0.0003). Conclusions: Intermittent dosing of enzalutamide in these mCRPC patients does not adversely impact OS, increasing time patients remain on treatment. However, this was a small, retrospective, single-centre study; prospective trials are necessary to clarify the role of intermittent enzalutamide.[Table: see text]

An analysis of survival in patients with castrate-resistant prostate cancer receiving enzalutamide with treatment breaks

2021 ◽  
pp. 205141582199376
Author(s):  
Michael P Rowe ◽  
Stuart Walter ◽  
Ayesha Hidayat ◽  
Adam Pollard ◽  
Timothy Norris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Time ◽  
Specific Antigen ◽  
Median Number ◽  
Start Time ◽  
Level Of Evidence ◽  
Significance Level ◽  
Castrate Resistant Prostate Cancer ◽  
Prospective Trials ◽  
Castrate Resistant

Objective: Enzalutamide is effective in treating metastatic castrate-resistant prostate cancer (mCRPC) but can have side effects that require treatment breaks (TB). We conducted a retrospective analysis of outcomes of patients who had extended TB due to toxicity compared to continuous dosing. Methods: Patients prescribed enzalutamide for mCRPC from September 2011 to February 2018 were included. TB was defined as an interruption of four weeks or more. Overall survival (OS) from enzalutamide start, time to prostate-specific antigen failure (TTF) and total enzalutamide treatment time (TTT) were analysed for TB and continuous responders (>50% PSA drop), and a significance level of 0.05 was assigned. Results: A total of 110 patients were continuous responders, and 29 had TB. The median number of interruptions was one (range 1–7), and time on treatment was 70% in the TB group. The TB group had significantly improved OS (100 vs. 60 months; hazard ratio=1.8, 95% confidence interval 1.17–2.77, p=0.02), prolonged TTF (median 11 vs. 6 months; p=0.008) and TTT (median 15 vs. 8 months; p=0.0001). Conclusion: Extended TB do not seem to impact OS or treatment duration adversely in patients who are responding and experiencing toxicity, and may be a useful option in managing toxicity. Prospective trials could explore this further. Level of evidence: Level 2c.

βIII-tubulin expression as a predictor of docetaxel resistance in metastatic castrate-resistant prostate cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15174-e15174
Author(s):  
Bertha E. Sanchez ◽  
Nilesh Gupta ◽  
Meredith Mahan ◽  
Evelyn R Barrack ◽  
Prem-veer Reddy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Clinical Decision Making ◽  
Performance Status ◽  
Ecog Performance Status ◽  
Docetaxel Resistance ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
The Mean ◽  
Castrate Resistant

e15174 Background: Docetaxel is a tubulin-targeting cytotoxic that remains first-line therapy in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) even though half of pts are reported to be non-responders. A predictive marker to identify those who will benefit from docetaxel-therapy will assist clinical decision making. High βIII-tubulin (TUBB3) expression has previously been reported to correlate with lack of response to taxanes in other cancers. We evaluated TUBB3 expression as a predictor of docetaxel-resistance in mCRPC. Methods: mCRPC pts treated with at least 3 cycles of docetaxel between 1990 and 2011 were identified retrospectively. TUBB3 immunostaining was performed on archival formalin-fixed, paraffin-embedded tissue. Stain intensity was scored from 0 to 3; 2 and 3 were interpreted as positive. Rates of PSA response were compared between pts with positive (+) and negative (-) TUBB3 expression. Two definitions of PSA response were evaluated (any PSA decline and at least 50% decline). Overall survival (OS) distribution between TUBB3+ and TUBB3- pts was estimated by the Kaplan-Meier method. Results: Of 73 pts, 26 (35%) expressed TUBB3. At diagnosis, the mean age was 65.7 years and the median Gleason score was 8. At the time of docetaxel therapy, the mean age was 71.2 years, the median PSA level was 70.9 (range, 0.2-5253) and 76% had ECOG performance status ≤1. The median number of docetaxel cycles was 7 (range, 3-18). The total dose of docetaxel was not different between groups (p=0.705). The median OS was 19.2 mo. TUBB3 expression was not correlated with any clinical or pathological characteristic (age, Gleason score, stage, ECOG, PSA, LDH, alkaline phosphatase, hemoglobin, visceral disease or chemotherapy before docetaxel). 65% of TUBB3+ pts had any PSA decline compared to 89% of pts with TUBB3- (p=0.0267). 52% of TUBB3+ pts had a PSA decline of ≥ 50% compared to 70% of TUBB3- pts (p=0.0144). Median OS for TUBB3+ pts was 16.8 mo compared to 20.4 mo in TUBB3- pts (p=0.039). Conclusions: High TUBB3 expression was associated with shorter OS and lower PSA response rates in mCRPC pts treated with docetaxel. These findings need to be validated prospectively.

Radium-223 in the treatment of metastatic castrate-resistant prostate cancer: A real-world Irish experience.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 228-228
Author(s):  
Niamh Peters ◽  
John Gaffney ◽  
Emma Connolly ◽  
Richard Bambury ◽  
Derek Gerard Power ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Alkaline Phosphatase ◽  
Real World ◽  
Median Number ◽  
Prior Chemotherapy ◽  
Factors Associated ◽  
Radium 223 ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

228 Background: Radium 223 (Ra-223) has been successfully utilised in the trial setting for the treatment of men with metastatic castrate resistant prostate cancer (mCRPC). To date, no real world outcomes from its use in the Irish population have been described. Methods: From September 2016 to March 2019, data from men referred for Ra-223 treatment at our institution was retrospectively collected. We recorded patient characteristics, treatments received and outcomes. Overall Survival (OS) was analysed using the Kaplan-Meier method. Results: 81 men were referred for Ra 223. Complete data was available for 56 men. Median age was 75. 79%(45/56) had over 6 bone metastases and 21%(12/56) had lymph node involvement. The median number of prior systemic treatments for mCRPC was 2. 84%(47/56) of patients were previously treated with Androgen deprivation therapy (ADT); 48%(27/56) Abiraterone, 36%(20/56) Docetaxel, 45%(25/56) Enzalutamide and 9%(5/56) Cabazitaxel. All patients were receiving bone protection agents; 57%(32/56) Zolendronic acid and 43%(24/56) Denosumab. Median ECOG was 1 at the start of treatment and 2 at completion. The median number of treatments received was 4 with 36%(20/56) completing all 6 treatments. The most common toxicity seen was grade1 fatigue occurring in10% (6/56). 17% (10/56) required a blood transfusion during their treatment course. 53%(30/56) required opioid analgesia prior to Ra 223 treatment. 76% of these men (22/30) described improved pain following Rad-223. At a median follow up of 13 months,41%(23/56) were alive. The median OS for the entire group was 7 months. Factors associated with improved OS included ECOG 0-1,fewer than 6 bone metastases, normal alkaline phosphatase level at start of treatment and no prior chemotherapy use. Median OS for those who had not received prior chemotherapy was significantly better than those who had (9 vs 5 months p=0.04). Conclusions: This real world study demonstrates Ra 223 is a well tolerated palliative treatment amongst Irish men with mCRPC. Good performance status, lower alkaline phosphatase, chemotherapy naivety and a low burden of metastatic disease are factors associated with an improved overall survival.

Development of a predictive model of PSA response to a switch from prednisone to dexamethasone in metastatic castrate-resistant prostate cancer patients biochemically progressing on abiraterone.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 88-88
Author(s):  
Reeta Barua ◽  
Cameron Phillips ◽  
Vanessa Sarah Arciero ◽  
Liying Zhang ◽  
Amanda Rahmadian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Performance Status ◽  
Multivariable Logistic Regression Analysis ◽  
Ecog Performance Status ◽  
Disease Characteristics ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

88 Background: Abiraterone acetate (AA) is typically administered with prednisone (P) to prevent symptoms of mineralocorticoid excess in patients with metastatic castrate resistant prostate cancer (mCRPC). After biochemical progression on AA + P, there is a sizeable subset of patients who have a renewed PSA response when switched from P to dexamethasone (D). The purpose of this study was to delineate clinical and pathologic factors that are predictive of a PSA response to such a steroid switch. Methods: We performed a retrospective analysis of 87 patients switched from AA+P to AA+D at Sunnybrook Odette Cancer Centre (Toronto, ON, Canada) between December 2012 and September 2018. Information on demographics, disease characteristics, previous treatments and performance status was collected. Response to the P to D switch maneuver was defined as a decrease in PSA by ≥30% within 12 weeks of the intervention (PSA30). Univariate logistic regression analyses were used to create a prediction model for each covariate tested, and R2 was applied for the measure of fit.Using multivariable logistic regression analysis and a backward stepwise selection procedure, we sought to identify patient and/or disease characteristics associated with a PSA30. Results: 38/87 patients (44%) experienced a PSA30. Univariate analysis showed that a favourable ECOG performance status, no prior docetaxel and no prior enzalutamide use were associated with a PSA30. On multivariable logistic regression analysis both favourable ECOG performance status and no prior enzalutamide use remained associated with a PSA30 (Table). Conclusions: A considerable proportionof patients with mCRPC who biochemically progress on AA+P have a renewed PSA response when changed to AA+D.Patients with a favourable ECOG performance status and no prior enzalutamide use are more likely to respond to such a steroid switch. Further prospective studies are needed to validate our findings.[Table: see text]

Docetaxel and imatinib every 21 days for castration resistant prostate cancer: A phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16086-e16086
Author(s):  
T. L. Gillison ◽  
L. J. Appleman ◽  
D. M. Friedland ◽  
T. L. Evans ◽  
P. N. Lara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Castration Resistant Prostate Cancer ◽  
Meaningful Improvement ◽  
Neutropenic Sepsis ◽  
Significant Toxicity ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

e16086 Background: Docetaxel (D) IV every 21 days, is the only cytotoxic agent that prolongs survival in men with castrate resistant prostate cancer (CRPC). Imatinib (I), a tyrosine kinase inhibitor, modulates PDGFR-ß in tumor vasculature. Based on phase I data from our institution, we hypothesized that D plus I would prolong time to progression (TTP) in patients (pts) with CRPC. Methods: Subjects with CRPC received D 60 mg/m2 IV every 21 days plus I 400 mg PO daily. After 10 pts, the study treatment was modified due to toxicity so that pts received I 400 mg on 10 of 21 days/cycle. The primary endpoint was TTP. Secondary endpoints were rate of PSA response and overall survival (OS). The sample size of 43 pts was designed to provide 90% power to detect an increase in TTP from 5 to 8 months. Results: 43 pts enrolled from 8/05 to 9/08. Age at enrollment ranged from 54–86 years (median 69 years). 14 pts received <1 cycle of D plus I and were unevaluable: 10 had significant toxicity, 4 due to non-treatment related reasons. Primary toxicities were hematologic: 21% G4 neutropenia, 5% G4 anemia, and no G4 thrombocytopenia. Fatigue, nausea, diarrhea, and electrolyte abnormalities were common, but <2 cases each of G3-G4 toxicity occurred. 1 case of G5 non-neutropenic sepsis occurred. 29 pts received >2 cycles of chemotherapy (mean 4.6). 12 pts had PR (41.4%), 9 had SD (31.0%), and 8 had no response (27.6%) by PSA. No objective responses were seen by CT imaging among 10 pts with measurable disease. 3 pts remain on trial. For evaluable pts, overall median TTP was 6.4 months (95% CL: 4.8, 8.4 months) compared with TTP of 5 months seen in previous trials. 23 (79%) pts had PSA progression, 3 pts died before progression, and 3 pts remain on trial. For all evaluable pts who had PR or SD by PSA (N = 21), median TTP was 7.1 months (95% CL: 5.5, 9.1 months). Median OS was 23.1 months (95% CL: 11.61 months, NR), compared with 18.9 months for GC Conclusions: Docetaxel on day 1 plus imatinib 10 days of each 21-day cycle resulted in meaningful improvement in TTP in the subset of pts who showed a response. Toxicity precludes its use in the general population, although its role in select pts with good performance status needs to be explored. [Table: see text]

C11-acetate PET for docetaxel prednisone (DP) response assessment in castrate-resistant prostate cancer (CRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15143-e15143 ◽  
Author(s):  
Nancy Sharma ◽  
Yusuf Menda ◽  
Laura Boles-Ponto ◽  
Daniel A. Vaena
Keyword(s):  
Prostate Cancer ◽  
Bone Scan ◽  
Response Assessment ◽  
Early Response ◽  
Median Number ◽  
Positron Emission ◽  
Psa Response ◽  
Castrate Resistant ◽  
A Prospective Study ◽  
Post Therapy

e15143 Background: C11- acetate (acetate) positron-emission tomogram (PET) has shown promise in detection of metastasis in prostate cancer in recent studies. Our study tested the feasibility of acetate-PET to predict early response to DP in CRPC. Methods: Men with metastatic CRPC for whom DP was indicated were enrolled in a prospective study of acetate-PET imaging and bone scans. Patients (pts) were imaged with both modalities at study entry and after 3 cycles of DP. DP was continued beyond cycle 3 until PCWG2-defined progression or toxicity. Treating physicians were blinded to acetate-PET results. No pts were on statins. The study was IRB-approved. Results: 6 pts with documented bone metastases were imaged (5 both pre and post-therapy.) Pre-therapy acetate-PET identified osseous metastases in all 6 pts. Remarkably, in one pt with previous radiation therapy, pre-therapy acetate-PET was negative for disease in the radiated area whereas bone scan showed persistent activity. The median number of DP cycles was 7 (5-16). 4 pts had ≥ 50% PSA decline. The median time to progression (TTP) was 5 months (mo). Of the 4 pts with PSA response, 2 had response on acetate-PET with TTP 5 mo and 10 mo respectively. One pt had > 50% PSA response but progression after 3 cycles based on PET, and met PCWG2 criteria for progression at 3.5 mo. The 4th pt with PSA response had stable findings on post-therapy PET and had 13 mo TTP. The pt who had no PSA response had stable post-therapy PET and had 2 mo TTP. Bone scan was stable in 3 pts, showed progression in 1pt and showed response in 1 pt. Conclusions: Response or progression on acetate-PET can be seen after a few chemotherapy cycles for CRPC. This study supports the exploratory inclusion of acetate-PET in future therapeutic clinical trials, with the potential to enhance the early prediction of treatment outcome. Acetate-PET might also allow more precise identification of viable target lesions than bone scan.

Enzalutamide after failure of docetaxel and abiraterone in metastatic castrate resistant prostate cancer (mCRPC): Results from an expanded access program.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 188-188 ◽  
Author(s):  
David Thomson ◽  
Natalie Charnley ◽  
Omi Parikh
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Progression Free Survival ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Biochemical Progression ◽  
Castrate Resistant ◽  
Access Program

188 Background: Abiraterone or enzalutamide are licensed for use post-docetaxel in metastatic castrate resistant prostate cancer (mCRPC). Both target the androgen receptor signalling pathway. There is little information describing their sequential use. Methods: Patients with mCRPC who had failed treatment with docetaxel and abiraterone received enzalutamide as part of an expanded access program. Patients were reviewed four weekly and post-treatment PSA used to determine efficacy. Results: Twenty three patients, median age 76 (range, 65 to 82), performance status of 1 (15/23) or 2 (8/23) with mCRPC (22/23 bone and 4/23 visceral disease) were enrolled. All had received prior docetaxel and abiraterone as well as cabazitaxel (35%), dexamethasone (30%), and stillboestrol (52%). Median biochemical progression free survival (bPFS) was 11.9 weeks. Nine (39%) patients showed sensitivity to enzalutamide, defined as a greater than 50% reduction in PSA. There was a correlation between PSA response to abiraterone and enzalutamide (R=0.45, p=0.03). In 10 out of 23 and 13 out of 23 patients who were sensitive and insensitive to abiraterone, 60% and 23% had a great than 50% reduction in PSA, respectively. There was a trend to improved bPFS in those sensitive to abiraterone (15.7 vs. 11.4 weeks, p=0.40) and in those who showed any PSA response to abiraterone (15.9 vs. 5.3 weeks, p=0.06). Conclusions: Enzalutamide has activity following failure of docetaxel and abiraterone in mCRPC. The effectiveness is more pronounced in those who have responded to abiraterone.

Characteristics and outcome of octogenarian versus young patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) treated with ketoconazole.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 256-256
Author(s):  
Victoria J. Sinibaldi ◽  
Michal Dadon-Nachum ◽  
Maya Gottfried ◽  
Natalie Maimon ◽  
Zamir Dovrish ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Partial Likelihood ◽  
Clinicopathologic Characteristics ◽  
Very Old ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Baseline Characteristics ◽  
Castrate Resistant

256 Background: Standard treatment options for patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) include docetaxel based chemotherapy, abiraterone, and radium 223. Octogenarian pts (age 80 and older) are often considered to be unfit for chemotherapy. However, recommendations for their management is limited by the paucity of clinical trials data in this population. In countries where abiraterone in the pre-chemotherapy setting has not been approved yet, or for pts who can’t afford it, the CYP 17 inhibitor ketoconazole is used as an alternative advanced hormonal tx. We aimed to study baseline characteristics and outcome of octogenarian versus young (age 60 or younger) pts with mCRPC treated with ketoconazole. Methods: We performed an international multicenter retrospective study of pts with mCRPC, who were treated with ketoconazole at four centers across two different countries. We compared baseline characteristics and outcome of octogenarian versus young pts. The effect of very old age on prostate-specific antigen (PSA) response, progression free survival (PFS), and overall survival (OS), was tested with adjustment of other known confounding risk factors using a chi-square test and partial likelihood test from Cox model. Results: Between 2004 and 2013, 35 octogenarians (median age 83) and 33 young pts with (median age 57) mCRPC were treated with ketoconazole. The groups were balanced regarding the following baseline clinicopathologic characteristics: extent of disease (limited-axial skeleton and/or nodal versus extensive-appendicular skeleton and/or visceral), combined gleason score, pre-treatment risk category (Keizman, Oncologist 2012; based on pre-tx neutrophil to lymphocyte ratio/prostate-specific antigen doubling time, and prior response to ADT), pain intensity, ECOG performance status, alkaline phosphatase level, hemoglobin level, PSA level. In octogenarian versus young pts, PSA response (greater than or equal to 50% decline from baseline) was 40% versus 61% (OR 3.5, p=0.04), median PFS 7 versus 8 months (HR 0.91, p=0.44), and median OS 31 versus 36 months (HR 0.66, p=0.31). Conclusions: In very old vs young mCRPC patients treated with ketoconazole, PSA response was lower. Baseline clinicopathologic characteristics, PFS, and OS were not significantly different between the groups.

Enzalutamide in men with prostate cancer resistant to docetaxel and abiraterone.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 247-247 ◽  
Author(s):  
Mark Creamer Scholz ◽  
Richard Y. Lam ◽  
Jeffrey S. Turner ◽  
Khang N. Chau ◽  
Lauren K. Becker ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stable Disease ◽  
Retrospective Chart Review ◽  
Early Access ◽  
Fda Approval ◽  
Heavily Pretreated ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Psa Progression ◽  
Castrate Resistant

247 Background: Since FDA approval in 2011, abiraterone (Zytiga) has supplanted docetaxel as preferred first-line treatment for metastatic castrate-resistant prostate cancer. In August 2012 enzalutamide (Xtandi) was FDA-approved for the treatment of castrate-resistant prostate cancer after docetaxel (Taxotere). We performed a retrospective chart review at a large medical oncology clinic specializing in prostate cancer to determine the PSA response rates of enzalutamide administered to men who had previously progressed on both abiraterone and docetaxel. This report includes some patients who participated in the Astellas/Medivation-sponsored Early Access Program; however, it represents the author’s independent clinical experience. Methods: Enzalutamide was administered at a dose of 160 mg daily. Patients were subsequently followed with monthly physical examination, PSA and routine blood tests. No hepatotoxicity or seizures occurred. Men were considered evaluable for PSA response if they received enzalutamide for twelve weeks. A PSA decline of 30% from baseline after 12 weeks was defined as a response. A PSA increase of 30% from baseline within 12 weeks was defined as disease progression. Men with neither a 30% increase nor a 30% decline were classified as having stable disease. Results: 66 men were treated and 63 were evaluable for PSA response. Median age was 67. Median baseline PSA was 68.5. All participants had disease that had progressed on abiraterone. 55 men received previous docetaxel. 38 had received previous Provenge. Two men stopped before 12 weeks because of intolerable fatigue. One man died of progressive disease before 12 weeks. After a median follow up of 12.5 weeks, 18(29%) men met criteria for PSA response. 13(21%) men had stable disease and 32(51%) men had PSA progression. Conclusions: Enzalutamide has activity in a heavily pretreated population of men resistant to abiraterone and docetaxel.

Exploring the effects of abiraterone/enzalutamide failure prior to the initiation of radium-223 dichloride in men with metastatic castrate-resistant prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 214-214 ◽  
Author(s):  
Patrick Cotogno ◽  
Elisa M. Ledet ◽  
Allie E. Steinberger ◽  
Rajasree Pia Chowdry ◽  
Michael Stolten ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Strong Association ◽  
Optimal Timing ◽  
Data Sets ◽  
Prognostic Variables ◽  
Kaplan Meier ◽  
Radium 223 ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

214 Background: FDA approval of three life-prolonging agents for metastatic castrate resistant prostate cancer (mCRPC) has occurred since April 2011. Two agents, abiraterone (abi) and enzalutamide (enza), disrupt androgen signaling. The third, radium-223 dichloride (Ra-223), targets bone metastases via alpha radiation. We sought to explore associations between prior abi/enza progression, number of Ra-223 cycles, prognostic factors, and overall survival (OS). Methods: Forty-two mCRPC patients (pts) treated with Ra-223 were identified. The sample was stratified based on progression (or not) on abi or enza prior to starting Ra-223. Number of Ra-223 doses administered, prognostic variables before Ra-223 treatment, and Kaplan-Meier estimates of overall survival (OS) were compared. Results: A strong association (p = 0.016) was demonstrated between prior abi/enza failure and number of Ra-223 doses administered. Patients without prior abi/enza failure were more likely to receive ≥ 4 doses of Ra-223 (94.12% vs 60.0%; odds ratio [OR] = 10.667; 95% CI, 1.214 – 93.699; p = 0.033). In comparison, those not receiving at least 4 doses of Ra-223 had a negative predictor in OS (p = .001) with a median survival of 89 days (n = 10; 95% CI, 44.064 – 133.936) compared to 303 days (n=15; 95% CI, 170.452 – 435.548). Patients initiating Ra-223 treatment after abi/enza progression had a higher median PSA (207.5 vs 49.2 ng/mL, p = 0.001), LDH (315 vs 253.5 U/L, p = 0.007) and alkaline phosphatase (ALP) (191 vs 106 U/L, p = 0.004). Conclusions: Our retrospective single institution analysis indicates that mCPRC patients who previously failed abi/enza are significantly less likely to complete 4 or more Ra-223 doses. These patients had significantly worse prostate cancer by a variety of standard prognostic variables. More information is needed from larger data sets to better understand this patient population and to best determine the optimal timing of Ra-223 administration.

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