Sequential use of new agents (NAs) after docetaxel (DOC) first line in metastatic castration-resistant prostate cancer (mCRPC) patients (pts): A pooled-analysis of the published studies.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 258-258 ◽  
Author(s):  
Francesca Maines ◽  
Orazio Caffo ◽  
Antonello Veccia ◽  
Emilio Bria
Keyword(s):  
Performance Status ◽  
Analysis Data ◽  
Pooled Analysis ◽  
Cross Resistance ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Visceral Metastases ◽  
Single Strategy ◽  
Selection Factors

258 Background: NAs have recently demonstrated a survival advantage in mCRPC pts progressing after DOC: two hormonal NAs (HNA), abiraterone and enzalutamide, and one chemotherapeutic agent, cabazitaxel (CAB). Recent evidences of possible cross-resistance has opened a debate about the best strategy when these drugs are used sequentially. We performed a pooled analysis of the published studies in order to assess if one of the following sequence strategy was potentially better than the others: a) HNA→ HNA, b) HNA → CAB or c) CAB → HNA. Methods: We evaluated the studies reporting clinical outcomes of a single NA administered after sequential treatment with docetaxel followed by another NA in mCRPC pts. All studies reporting monthly overall survival (OS) rates were considered eligible for the analysis; data were extracted, cumulated and weighted by taking into account each trial sample. We also evaluated possible differences in terms of factors able to produce potential patient-selection biases (age, Performance Status, visceral metastases and Gleason score). Results: Ten retrospective studies met the selection criteria of our analysis. They reported the outcomes of 735 pts who have received HNA → HNA (320 pts), HNA→ CAB (249 pts), and CAB → HNA (166 pts). No statistically significant differences were observed in terms of selection factors. Cumulative OS rates (with CIs), according to treatment sequence, are summarized in the Table. Conclusions: Our data seems to confirm a potential cumulative survival benefit of sequential use of NAs without a clear superiority of a single strategy over the others after DOC first-line in mCRPC patients. This conclusion is tempered by the retrospective nature and the potential selection biases. Nevertheless, a possible OS advantage could be observed when a CAB-based sequence is adopted. [Table: see text]

Use of epirubicin, carboplatin, and 5-fluorouracil (ECarboF) as a second-line treatment in metastatic castration-resistant prostate cancer.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 173-173
Author(s):  
U. B. McGovern ◽  
S. J. Harland
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Performance Status ◽  
Median Number ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Docetaxel Chemotherapy ◽  
Line Chemotherapy

173 Background: ECarboF chemotherapy is an active first line chemotherapy treatment for metastatic prostate cancer. We have now investigated its efficacy and toxicity in patients who have progressed during or after docetaxel chemotherapy. Methods: 37 patients with metastatic prostate cancer who had received ECarboF chemotherapy were retrospectively reviewed from a five year period (2005-2010). All patients had previously received first-line docetaxel chemotherapy and had either progressed following treatment (n=17) or were docetaxel refractory (n=20). Patients received epirubicin 50mg/m2 iv d1, carboplatin (AUC 5) d1, fluorouracil 440mg/m2 d1, d15 and folinic acid 20mg/m2 d1, d15 on a q4w cycle. 20% dose reductions were made for the first cycle in patients with poorer performance status. PSA was measured before each cycle of treatment and all patients were assessed for toxicity. Results: Patients had a median age of 70 years (range 48-77), median baseline PSA of 226.5 ng/mL (range 9.6-1,580) and the median number of ECarboF chemotherapy cycles received was 6 (range 1-10). 65% (n=24) of patients were ECOG 0-1, the remaining 35% (n=13) were ECOG 2-3. 16% (n=6) patients had a ≥ 30% decline in PSA and 16% (n=6) patients had a ≥ 50% decline in PSA. 35% (n=13) of patients experienced grade 3/4 toxicity, most commonly anaemia (13.5%), neutropenia (13.5%) and thrombocytopenia (8.1%) with one treatment related death (neutropenic sepsis) during the five year period analysed. Median time to PSA progression was 5.1 months. Conclusions: ECarboF has activity with acceptable toxicity post docetaxel in the treatment of metastatic castration resistant prostate cancer. Although PSA response rates are modest, the time to progression is comparable to that of more toxic regimens. ECarboF should be considered as an active second-line chemotherapy regimen. No significant financial relationships to disclose.

Experience with sipuleucel-T in metastatic castration-resistant prostate cancer (mCRPC) with visceral spread from PROCEED.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 174-174
Author(s):  
Nicholas J. Vogelzang ◽  
Philip W. Kantoff ◽  
Mark C. Scholz ◽  
Jeffrey L. Vacirca ◽  
Shaker R. Dakhil ◽  
...  
Keyword(s):  
Performance Status ◽  
Specific Antigen ◽  
Cellular Immunotherapy ◽  
Castration Resistant Prostate Cancer ◽  
Phase 3 ◽  
Castration Resistant ◽  
Visceral Metastases ◽  
Antigen Presenting ◽  
Post Hoc ◽  
Clinical Trial Information

174 Background: Trials of approved agents in mCRPC have reported shorter overall survival (OS) in men with visceral metastases (mets). The phase 3 IMPACT trial evaluated sipuleucel-T, an autologous cellular immunotherapy, in mCRPC but excluded visceral mets. PROCEED, a registry of mCRPC patients receiving sipuleucel-T, offers the first description of sipuleucel-T in patients with visceral mets. Methods: PROCEED enrolled men with mCRPC treated with sipuleucel-T biweekly x 3. Dose adjustment for organ dysfunction was unnecessary. Men were followed until death, study withdrawal, or a minimum of 3 years. OS is reported in this post-hoc subgroup analysis. Results: 1902 men received ≥1 sipuleucel-T infusion between 2011-2014. Visceral mets (n = 90) included liver (n=21), lung (n=61), and brain (n=2) involvement. Compared to patients without visceral mets (Table), men with visceral mets had poorer performance status (PS) and higher baseline prostate-specific antigen (PSA). Median OS was 20.5 and 31.2 mo in those with and without visceral mets. Patients with liver and lung mets had a median OS of 16.3 and 21.0 mo, respectively. Activation of antigen-presenting cells, a measure of immune activation and product potency, was similar in those with and without visceral mets. Conclusions: Initial observations suggest that patients with mCRPC and visceral spread can activate their immune cells to produce sipuleucel-T, but have a shorter OS than those with bone and/or lymph node spread. (NCT01306890). Clinical trial information: NCT00065442. [Table: see text]

Response to abiraterone acetate in the postchemotherapy setting in patients with castration-resistant prostate cancer whose disease progresses early on docetaxel.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 17-17 ◽  
Author(s):  
Deborah Mukherji ◽  
Carmel Jo Pezaro ◽  
Diletta Bianchini ◽  
Andrea Zivi ◽  
Johann Sebastian De Bono
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Abiraterone Acetate ◽  
Cross Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Progression Of Disease ◽  
Psa Response ◽  
Visceral Metastases ◽  
Radiological Response

17 Background: Abiraterone acetate (AA) has recently been approved for men with metastatic castration-resistant prostate cancer (CRPC) following docetaxel chemotherapy. AA inhibits CYP17, reducing androgen production and thereby impacting androgen receptor (AR) signalling. Recent evidence suggests taxanes also impact AR signalling, raising concerns about potential cross-resistance. We have previously shown that docetaxel has no antitumor activity in AA refractory patients. We have now evaluated the antitumor activity of AA post-docetaxel to determine the activity of AA in docetaxel refractory patients. Methods: Forty four men with CRPC treated with docetaxel (75 mg/m2 every 21 days) followed by post-chemotherapy AA at the Royal Marsden Hospital were identified. Radiological response by RECIST, PSA response by PSAWG2 criteria and symptomatic benefit were evaluated. Results: An average of 9 cycles of docetaxel were given (range 3-17); 7 patients discontinued chemotherapy due to progression of disease and 10 for toxicity. Of 40 patients with PSA data available, 26 (65%) had a PSA decline of at least 50%. At commencement of AA, median age was 68 years. Bone, nodal and visceral metastases were present in 38 (86%), 23 (52%) and 6 (14%) of the cohort respectively. An average of 5 months of treatment were delivered and 23 patients continue on AA. Of the 44, 7 (16%) patients had a 50% or greater PSA decline on AA. None of the 7 patients who were docetaxel refractory had a subsequent PSA, radiological or clinical response to AA. Of the 6 patients who received less than 5 cycles of docetaxel due to toxicity, 2 had subsequent PSA response on AA. There was no relationship between length of time on LHRH agonist and PSA response to AA. Conclusions: Our data suggest that patients who are refractory to docetaxel do not respond to AA. Overall, in conjunction with our other evidence that in AA-refractory patients docetaxel has no antitumor activity, these data provide further evidence for cross-resistance between these two agents.

Sequencing radium 223 (RA223) for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) in the daily practice: Preliminary results from a retrospective study in Italian centers.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 322-322 ◽  
Author(s):  
Orazio Caffo ◽  
Viviana Frantellizzi ◽  
Luca Galli ◽  
Fabio Monari ◽  
Gaetano Facchini ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Objective Response ◽  
Daily Practice ◽  
Cross Resistance ◽  
Consecutive Series ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Radiation Mechanism ◽  
Castration Resistant ◽  
Radium 223

322 Background: The potential advantage of the sequential use of the active drugs (ADs) able to prolong overall survival (OS) in mCRPC (abiraterone, cabazitaxel, docetaxel, enzalutamide, RA223) could be limited by the development of common mechanisms of resistance. According to its unique targeted alpha-radiation mechanism of action, it could be postulated that RA223 does not induce and is not affected by cross-resistance with other agents and consequently its incorporation in therapeutic sequences may improve clinical outcomes. The present study is aimed to describe the clinical outcomes of pts who received RA223 and at least two other ADs for mCRPC. Methods: We collected data of pts who received sequentially 3 or more ADs of which one was RA223. For each pt we recorded the clinical outcome of all treatments received for mCRPC. We also compared the cumulative survival from the start of the first line to that of a contemporary series of 405 mCRPC pts without visceral mets sequentially treated with 3 or 4 ADs not comprising RA223. Results: A consecutive series of 119 mCRPC pts was collected: the median age was 72 yrs. Six pts received all 5 available ADs, 53 pts 4 ADs, and the remaining pts 3 ADs. Most of the pts received RA223 as the 3rd or 4th line of treatment (62 and 42, respectively), and the remaining were treated in less or more advanced lines (10 and 5 pts respectively). Overall the full 6-cycle treatment was completed in 61 pts (51.3%) and in 61.3% and 38.1% of pts when Ra223 was administered as 3rd and 4th treatment line respectively (p = 0.02). Partial response and stable disease as best objective response to RA223 was achieved in 11.3% and 24.5% of pts respectively, while a PSA reduction of ≥ 50% was observed in 7.2% of pts. Median OS from the start of the first line was 48 mos. In pts treated with 3 or 4 ADs that included Ra223, the median OS was significantly longer compared to that of pts whose treatment sequence did not include RA223 (48.4 vs 39.2 mos, p = 0.03). Conclusions: Despite the limitations of its retrospective nature, this preliminary data suggests that treatment sequencing of ADs that includes RA223 offers a survival advantage in mCRPC.

Triweekly docetaxel versus biweekly docetaxel as a treatment for advanced castration resistant prostate cancer: Quality of life analysis.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 23-23 ◽  
Author(s):  
Pirkko-Liisa Irmeli Kellokumpu-Lehtinen ◽  
Ulrika Harmenberg ◽  
Petteri Hervonen ◽  
Timo K. Joensuu ◽  
Raymond S. McDermott ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Performance Status ◽  
Line Treatment ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Weekly Docetaxel ◽  
Castration Resistant ◽  
First Line Treatment

23 Background: Bi-weekly docetaxel (T) with prednisone improved progression free survival and overall survival when compared with the standard tri-weekly T as first-line treatment for advanced castration resistant prostate cancer (CRPC) (Lancet Oncol. 2013;14:117-124). We report here the quality of life (QoL) results of this prospective randomized trial. Methods: Three hundred and forty-six patients were randomly allocated centrally to receive intravenous therapy T of either 75 mg/m² d1 q3 wks (the triweekly arm) or 50 mg/m² d1 and d 14, q4 wks (the biweekly arm) (identifier NCT00255606). Prednisone (10 mg/d) was administered orally in both groups. The baseline patients characteristics were well balanced between the groups with respect to the performance status, mean age (69, range 45 to 87 vs. 68, range 46 to 85), and median serum prostate-specific antigen (PSA) content (109 µg/L, range 11 to 1,230 vs. 116 µg/L, range 12 to 1,870). Quality of life (QoL), the frequency and severity of symptoms including pain were assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) version 4.0 questionnaire. Results: The baseline (QoL) of both treatment groups was compared to QoL after six months of the treatment within each treatment group and between groups. Changes in fatigue, symptoms of pain and nausea, and the overall performance status did not differ between the groups. There were statistically significant differences in overall quality of life values (p=0.010) and discomforting pain values (p=0.028) favoring the bi-weekly treatment arm. Conclusions: Bi-weekly T is better tolerated than the tri-weekly standard T. Following the results from the clinical outcome and the QoL outcome in the PROSTY trial we would recommend the use of bi-weekly docetaxel as first line treatment of CRPC Clinical trial information: NCT00255606.

scholarly journals Efficacy and Safety of Docetaxel in Elderly Patients With Metastatic Castration-Resistant Prostate Cancer

2018 ◽  
pp. 1-9 ◽  
Author(s):  
Manuel Caitano Maia ◽  
Allan A. Lima Pereira ◽  
Liana Valente Lage ◽  
Natalia Moreno Fraile ◽  
Victor Van Vaisberg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Elderly Patients ◽  
Performance Status ◽  
Specific Antigen ◽  
Age Groups ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Line Chemotherapy

Purpose Limited data are available about the tolerability and clinical outcomes of elderly patients with metastatic castration-resistant prostate cancer (mCRPC) who are treated with docetaxel. We evaluated the efficacy and safety of docetaxel as first-line chemotherapy for patients with mCRPC who were treated in our institution. Materials and Methods We retrospectively identified patients with mCRPC and a Karnosfky performance status of 60% or greater treated with docetaxel on any schedule as first-line chemotherapy between 2008 and 2013. The primary end point was a comparison of median overall survival (OS) according to age in this population. Secondary end points were comparisons of the rates of severe toxicities, prostate-specific antigen (PSA) decline of 50% or greater, and time to progression (TTP). Results were stratified by three age groups: younger than 65 years, 65 to 74 years, and 75 years or older. Results Among the 197 patients included, 68 (34%) were younger than 65 years, 85 (43%) were 65 to 74 years, and 44 (22%) were 75 years or older. The mean number of comorbidities was not different among groups (1.19 v 1.32 v 1.43; P = .54). Patients younger than 65 years received a higher cumulative dose of docetaxel (450 mg/m2 v 382 mg/m2 v 300 mg/m2; P = .004). The rates of PSA decline of 50% or greater (41% v 47% v 36.4%; P = .51) and the median TTP (5.13 v 5.13 v 4.7 months; P = .15) were comparable among all groups. The median OS was longer in the group of patients younger than age 65 years (19.6 v 12.4 v 12.3 months; P = .012). Rates of any grade 3 or higher adverse event were not different among groups (63.2% v 71.8% v 54.5%; P = .14). Conclusion Administration of docetaxel in elderly patients who had good performance status was well tolerated. Rates of PSA decline and TTP were similar to those of younger patients, but median survival was lower.

scholarly journals Early Prostate-Specific Antigen (PSA) Change at Four Weeks of the First-Line Treatment Using Abiraterone and Enzalutamide Could Predict Early/Primary Resistance in Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 526
Author(s):  
Taizo Uchimoto ◽  
Kazumasa Komura ◽  
Wataru Fukuokaya ◽  
Takahiro Kimura ◽  
Kazuhiro Takahashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multivariate Analysis ◽  
Performance Status ◽  
Specific Antigen ◽  
Line Treatment ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Primary Resistance ◽  
Castration Resistant ◽  
First Line Treatment

The identification of early or primary resistance to androgen signaling inhibitors (ASIs) is of great value for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the predictive value of prostate-specific antigen (PSA) response at dour weeks of first-line ASIs treatment for mCRPC patients. A total of 254 patients treated with ASIs (abiraterone acetate: AA and enzalutamide: Enz) at the first-line treatment are retrospectively analyzed. Patients are stratified according to the achievement of >30% PSA decline at 4 and 12 weeks from the treatment initiation. At four weeks of the treatment, 157 patients (61.8%) achieved >30% PSA decline from the baseline. Thereafter, 177 patients (69.7%) achieved >30% PSA decline at 12 weeks of the treatment. A multivariate analysis exhibits >30% PSA decline at four weeks as an independent predictor for overall survival (OS). We note that 30 of 97 (30.9%) patients who did not achieve >30% PSA decline at four weeks consequently achieved >30% PSA decline at 12 weeks, and had a comparable favorable three years OS rate as the 147 patients achieving >30% PSA decline at both 4 and 12 weeks. To identify the variables that discriminate the patient survival in 97 patients without achieving >30% PSA decline at four weeks, a multivariate analysis is performed. The duration of androgen deprivation therapy before CRPC ≤ 12 months and Eastern Cooperative Oncology Group Performance Status ≥ 1 are identified as independent predictors for shorter OS for those patients. These data offer a concept of early treatment switch after four weeks of first-line ASIs when not observing >30% PSA decline at four weeks—particularly in patients with a modest effect of ADT and poor performance status.

Mental health care utilization among veterans with castration-resistant prostate cancer receiving abiraterone or enzalutamide.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18680-e18680
Author(s):  
Phoebe A. Tsao ◽  
Jennifer A. Burns ◽  
Shami Entenman ◽  
Kyle Kumbier ◽  
Jordan Sparks ◽  
...  
Keyword(s):  
Mental Health ◽  
Prostate Cancer ◽  
Health Care ◽  
Mental Health Care ◽  
Health Administration ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Diagnostic Characteristics ◽  
Comorbidity Burden

e18680 Background: Abiraterone and enzalutamide are oral therapies widely used to treat men with castration-resistant prostate cancer (CRPC). Recent data have suggested potentially worsened quality of life and depression with use of enzalutamide compared to abiraterone. Because Veterans are at a higher risk for mental health conditions, we sought to compare mental health service utilization in Veterans with CRPC receiving enzalutamide to those receiving abiraterone. Methods: The Veterans Health Administration Corporate Data Warehouse was used to identify men with CRPC who received abiraterone or enzalutamide for ≥ 30 days as first-line treatment between 2010-2017. We compared the rate of mental health visits per 100 patient-months for men on abiraterone versus enzalutamide using an exact rate ratio test, assuming Poisson counts. Results: Among 2902 male Veterans, 68.6% (n=1992) received abiraterone and 31.4% (n=910) enzalutamide as first-line therapy. Men who received enzalutamide were older (76 vs 74, p<0.01) and had a higher comorbidity burden (Charlson Comorbidity Index [CCI] ≥ 2 in 28.7% vs 21.6%, p<0.01); no differences were noted in race or prevalence of preexisting documented mental health diagnoses. Median time on drug was 8 months for both medications. There was no difference in the rate of mental health visits per 100 patients-months on enzalutamide versus abiraterone (6.6 v. 6.7, p=0.66). However, within patient sub-groups, men who were age 75 or older, not married, or without notable comorbidities had lower rates of mental health visits with enzalutamide compared to abiraterone; whereas those who were younger than 75, married, had higher comorbidities, or a preexisting mental health diagnosis had higher rates of mental health visits with enzalutamide (Table). Conclusions: Among Veterans with CRPC who received a novel antiandrogen therapy first-line, there was no difference in engagement in mental health care between those who received abiraterone versus enzalutamide. Sub-group analysis revealed significant differences between patients on the two medications in demographic and diagnostic characteristics associated with number of visits, suggesting that vulnerability for mental health symptoms may vary by medication type. Further work in understanding the long-term impact of novel antiandrogens on mental health is needed.[Table: see text]

Sign in / Sign up

Export Citation Format

Share Document