Primary resistance to abiraterone acetate (AA) after docetaxel treatment in metastatic castration-resistant prostate cancer (mCRPC): A multicenter retrospective analysis.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 206-206
Author(s):  
Marco Maruzzo ◽  
Umberto Basso ◽  
Alberto Diminutto ◽  
Ugo De Giorgi ◽  
Lucia Fratino ◽  
...  
Keyword(s):  
Performance Status ◽  
Treatment Strategies ◽  
Poor Performance ◽  
Abiraterone Acetate ◽  
Poor Performance Status ◽  
Consecutive Series ◽  
Castration Resistant Prostate Cancer ◽  
Primary Resistance ◽  
Early Progression ◽  
Docetaxel Treatment

206 Background: AA improves survival in mCRPC patients pre-treated with docetaxel. All patients eventually become resistant at different interval times, but some of them show an early progression and should be considered as primary resistant (PRES). To date, no factors have been identified as predictive of primary resistance. Methods: The clinical outcomes of a consecutive series of patients treated with AA after docetaxel failure in 19 Italian Hospitals within a Named Patient Program (NPP) was previously reported (BJU 2014). In the present analysis, we focus on patients who achieved an investigator-assessed PFS ≤ 3 months (PRES) and those with PFS ≥ 12 months (long term responders, LR). The main aim is to determine clinical characteristics associated with primary resistance. Results: Among the 265 patients enrolled in the NPP, we identified 97 PRES (37%) and 71 LP (27%). Poor performance status, visceral metastases, presence of pain, low baseline haemoglobin level, increased LDH and ALP levels, and short time from diagnosis to AA therapy were significantly associated with early progression (Table). Conclusions: Several clinical parameters appear to correlate with early progression under AA. Their role as potential predictive factors of resistance deserve further exploration in order to develop alternative treatment strategies. [Table: see text]

Prevention of docetaxel-associated febrile neutropenia with primary granulocyte colony-stimulating factors (GCSF) in Chinese metastatic hormonal-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 72-72
Author(s):  
Darren M.C. Poon ◽  
Kuen Chan ◽  
T.W. Chan ◽  
Bryan Ng ◽  
S Wai-kwan Siu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Febrile Neutropenia ◽  
Performance Status ◽  
Poor Performance ◽  
Chinese Patients ◽  
Poor Performance Status ◽  
Castration Resistant Prostate Cancer ◽  
Increased Risk ◽  
Docetaxel Treatment ◽  
Life Threatening

72 Background: Plenty reports suggest Asian prostate cancer patients are more susceptible to docetaxel-related febrile neutropenia (FN). However, primary GCSF prophylaxis is currently not recommended by international guidelines for patients with mCRPC or mHSPC when docetaxel is administered. Therefore, we aim to evaluate the potential benefit of primary GCSF in preventing the potentially life-threatening FN for Chinese mHSPC and mCRPC treated with docetaxel. Methods: Two cohorts (2003-2012 & 2015-2018) that consisted of Chinese patients with mHSPC and mCRPC who had docetaxel at six public oncology centres in Hong Kong were grouped and analysed. Primary GCSF was defined as its administration within 5 days of beginning docetaxel, and its use was at the discretion of oncologists. The primary outcome was FN within 21 days of first cycle of docetaxel (1st FN). Multivariable regression analysis was used. Results: A total of 377 metastatic prostate cancer (mHSPC, n=100 (26%); mCRPC, n=277 (73%)) patients with docetaxel treatment was identified. Primary GCSF was given in 71 (18%) patients. The baseline characteristics were balanced between groups with and without primary GCSF. FN was happened in 61 patients (16%), with 37 (9%) of them at 1st cycle. Primary GCSF were administered in 2 and 69 patients with and without 1st FN, respectively (5.4% vs 20.3%, p=0.03). Primary GCSF was associated with reduced risk of 1st FN (odds ratio (OR), 0.22; 95% CI 0.05 - 0.96; p=0.04) in overall, and a similar trend was observed in both mHSPC (OR, 0.36; p=0.35) and mCRPC (OR, 0.16, p=0.08) subgroups. Besides, among various clinical parameters, poor performance status (ECOG 2-3) was associated with increased risk of 1st FN (OR, 3.90, 95% CI 1.66 – 9.13, p=0.002). Conclusions: Primary GCSF prophylaxis is suggested for Asian mCRPC and mHSPC patients, particularly those with poor performance status, to alleviate the risk of docetaxel-related febrile neutropenia.

scholarly journals Stunning Response with Low-Dose Enzalutamide after Abiraterone Acetate Failure in a Patient Diagnosed with Metastatic Castration-Resistant Prostate Cancer: A Case Report

2021 ◽  
pp. 634-640
Author(s):  
Luigi Rossi ◽  
Giuseppe Cimino ◽  
Elisa Gozzi ◽  
Marsela Sinjari ◽  
Martina Brandi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Low Dose ◽  
Performance Status ◽  
Poor Performance ◽  
Abiraterone Acetate ◽  
Poor Performance Status ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Biochemical Progression ◽  
Lh Rh

We report a case of an elderly patient with metastatic castration-resistant prostate cancer, initially treated with abiraterone acetate (1,000 mg/day) combined with LH-RH antagonist, prednisone (10 mg/day), and zoledronic acid to manage bone metastases. In consideration of his poor performance status, radiological and biochemical progression of the disease, we decided to switch abiraterone to enzalutamide (160 mg/day). Due to adverse events, we reduced enzalutamide to a dose of 80 mg/day. Currently, the disease is under control despite the use of a low dose of enzalutamide.

Outcomes with Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Who Have Poor Performance Status

2015 ◽  
Vol 67 (3) ◽  
pp. 441-447 ◽  
Author(s):  
Arun A. Azad ◽  
Bernhard J. Eigl ◽  
Raya Leibowitz-Amit ◽  
Renee Lester ◽  
Christian Kollmannsberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Performance Status ◽  
Poor Performance ◽  
Abiraterone Acetate ◽  
Poor Performance Status ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Looking to possible predictive factors of primary resistance to abiraterone acetate (AA) and enzalutamide (ENZ) in pretreated patients (pts) with castration-resistant prostate cancer (CRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 248-248
Author(s):  
Orazio Caffo ◽  
Antonello Veccia ◽  
Francesca Maines ◽  
Alberto Bonetta ◽  
Gilbert Spizzo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Univariate Analysis ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Consecutive Series ◽  
Continuous Variables ◽  
Castration Resistant Prostate Cancer ◽  
Primary Resistance ◽  
Castration Resistant ◽  
Chi Square Analysis

248 Background: Abiraterone acetate (AA) and enzalutamide (ENZ) are new generation hormonal agents (NHA) which demonstrated a survival gain in patients (pts) with castration-resistant prostate cancer (CRPC) pre-treated with docetaxel. Although all patients eventually became resistant to these NHAs, some of them show primary resistance, defined as an early progression within the first 3 months, which leads to an early treatment interruption. In the present analysis we have tried to identify which factor, if any, may predict primary resistance to AA and ENZ. Methods: We evaluated a consecutive series of 57 pts, treated in our hospital in two successive named patient programs conducted in our hospital to allow pre-treated CRPC patients to receive NHAs before their approval in Italy: 26 received AA (1,000 mg po + prednisone 10 mg po daily) and 31 ENZ (160 mg po daily). For each pt we have recorded the pre- and post-NHA clinical history, the treatment details and outcomes. We have also assessed the ability of a series of 24 selected clinical factors to predict NHAs resistance, through a logistic regression analysis. Continuous variables were categorized by quartiles and chosen for the initial model after a univariate chi-square analysis. Results: Among the 24 factors, the presence of pain at baseline, high baseline lactate dehydrogenase levels and prostate-specific antigen (PSA) levels after one month of treatment were predictive of primary NHA resistance at the univariate analysis. However, only PSA levels were confirmed at the multivariate analysis [exp(beta) 0.115; p = 0.007], as patients failing to achieve a 50% or more reduction in baseline PSA levels, were more likely to show primary NHA resistance (48% vs. 15%). Conclusions: Our results suggest that PSA trend may represent a simple and rapid method of identifying patients with primary resistance to NHAs, so patients failing to achieve a 50% or more reduction within the first month of treatment should undergo intensive investigations, to verify whether they have primary resistance to NHAs. These data should be confirmed in a larger patient population.

Patient risk factors and pegfilgrastim use in cabazitaxel-treated prostate cancer pateints in an academic setting.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 224-224
Author(s):  
Marina Dusevic Kaymakcalan ◽  
Sherri Stuver ◽  
Christopher Sweeney ◽  
Toni K. Choueiri ◽  
Aymen Elfiky
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Performance Status ◽  
Poor Performance ◽  
Prior History ◽  
Poor Performance Status ◽  
Castration Resistant Prostate Cancer ◽  
Exact Test ◽  
Potential Risk Factors ◽  
The Impact

224 Background: Cabazitaxel can offer a survival advantage in patients (pts) with metastatic castration resistant prostate cancer (mCRPC). Febrile neutropenia (FN) has emerged as a serious complication, with a rate of 8% in the TROPIC trial (de Bono, Lancet 2010). Prophylaxis with pegfilgrastim (P) can decrease the risk of FN, although predictors of FN continue to evolve. We performed an analysis on the effect of prophylactic P use on FN and the impact of certain risk factors on FN rates. Methods: We conducted a retrospective analysis of mCRPC patients treated with cabazitaxel from June 2010 to August 2013 at Dana-Farber Cancer Institute. Patient clinical and treatment variables were extracted. Fisher’s exact test was used to evaluate the association between potential risk factors and FN. Results: A total of 89 patients were treated at our institution and included in this analysis. All patients received at least one dose of cabazitaxel and received a mean of four cycles. Five pts (5.6%) developed FN; 3 out of 70 (4.3%) receiving P and 2 out of 19 (10.5%) not receiving P (p=0.3). Of the 24 patients that started cabazitaxel at a reduced dose, none developed FN. No toxic death was reported. Among several risk factors including P use, age older than 65, pre-existing neutropenia, prior chemotherapy, pre-existing infection, poor performance status, liver and renal dysfunction, and recent surgery, only a prior history of palliative radiation had a significant association with FN (p=.002). Conclusions: The rate of FN in a large academic practice is similar to what was reported in the TROPIC trial. Prior radiation may be a risk factor for FN in cabazitaxel-treated mCRPC patients. Other factors that may help better predict the risk of FN in different groups of patients receiving cabazitaxel must be identified.

Application of abiraterone acetate (AA) in chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) patients who did not fulfil the patient inclusion criteria in the COU-AA-302 study.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 317-317
Author(s):  
Darren M. C. Poon ◽  
Chan Kuen ◽  
S.H. Lee ◽  
T.W. Chan ◽  
Chun-Kin Sze ◽  
...  
Keyword(s):  
Performance Status ◽  
Poor Performance ◽  
Abiraterone Acetate ◽  
Poor Performance Status ◽  
Inclusion Criteria ◽  
Study Results ◽  
Significant Difference ◽  
Visceral Metastases ◽  
Clinical Records ◽  
The Impact

317 Background: Visceral metastases or poor performance status (ECOG 2 or above) were the major exclusion criteria in the COU-AA-302 study, and hence the efficacy of abiraterone acetate (AA) in chemo-naïve mCRPC patients with these characteristics remain undetermined. Our study compares the clinical efficacy of AA in chemo-naïve mCRPC patients with or without the aforementioned characteristics. Methods: The clinical records of chemo-naïve mCRPC patients from all 6 public oncology centers in Hong Kong between August 2011 and December 2014 were reviewed. Patients with visceral disease who were medically unfit for, or who declined, chemotherapy, were allowed for AA in the study period. The median overall survival (OS), progression-free survival (PFS), patient and disease characteristics were compared between groups which satisfied, and did not satisfy, the inclusion criteria of COU-AA-302 study. Results: Fifty-eight consecutive chemo-naïve mCRPC patients had received AA in the review period, of which 29 fulfilled the inclusion criteria for the COU-AA-302 study (Group Eligible). All the remaining patients (Group Ineligible) had ECOG 2 or above, including 3 who had non-nodal visceral metastases. Group Ineligible had higher baseline PSA, haemoglobin and alkaline phosphatase level than Group Eligible, but otherwise there was no significant difference in the baseline characteristics between the groups for age, Gleason score, and co-morbidities. Group Ineligible had significantly shorter OS than Group Eligible (7.7 vs 25.0 months, p = 0.0095) and also a shorter PFS that did not reach statistical significance (5.3 vs 9.8 months, p = 0.2936). The duration of use of AA, and frequency of employment of post-AA treatment were comparable between the groups. Conclusions: Our study demonstrated a poor efficacy of AA in chemo-naïve patients who did not fulfil the inclusion criteria for COU-AA-302 study, by virtue of poor performance status or presence of visceral metastases. The impact of AA in this group of patients warrants further examination in clinical trials before its routine clinical use in this subgroup.

Sequential administration of new agents (NAs) after docetaxel (DOC) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts): Impact of disease control (DC) duration in second line on the subsequent line outcomes.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 210-210
Author(s):  
Francesca Maines ◽  
Ugo De Giorgi ◽  
Gaetano Facchini ◽  
Lucia Fratino ◽  
Donatello Gasparro ◽  
...  
Keyword(s):  
Disease Control ◽  
Clinical Outcomes ◽  
Abiraterone Acetate ◽  
Consecutive Series ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Primary Resistance ◽  
Sequential Administration ◽  
Progression Of Disease ◽  
Third Line

210 Background: Abiraterone acetate (AA), cabazitaxel (CABA), and enzalutamide (ENZ) are NAs which demonstrated their efficacy in mCRPC pts who have previously treated with DOC. Unfortunately all pts develop a resistance to these drugs and eventually show a progression of disease. Since the androgen receptor machinery remains the ultimate target of NAs in mCRPC post-DOC, some mechanisms of resistance could be common to all NAs. To date, NAs are sequentially administered in the hope of obtaining a cumulative survival benefit. To date it is unknown if the DC duration influence the outcomes of the subsequent treatments. The present study was aimed to retrospectively assess this issue in a large series of mCRPC pts. Methods: We recorded the clinical outcomes of all treatments received after DOC. For the study purpose, we categorized the pts according to the duration of DC (absence of progression) during NA-based second line: DC ≤ 3 mos (primary resistance – PRe); DC from 3.1 to 11.9 mos (intermediate sensitivity – IS); DC ≥ 12 mos (long term disease control – LTDC). Results: A consecutive series of 291 mCRPC pts, median age 71 yrs (46-91), with bone (88%), nodal (53%) or visceral (18%) mets, was collected. All pts received a NA-based as second line after DOC: 160 (55%) received AA, 99 (33%) CABA and 32 (11%) ENZ. PRe was observed in 56 pts (23 AA – 25 CABA – 8 ENZ), IS in 178 (101 AA – 58 CABA – 19 ENZ), LTDC in 57 (36 AA – 16 CABA – 5 ENZ). The third-line clinical outcomes are detailed in the table. Conclusions: From this data, it appears that DC duration may be a prognostic factor, as a probable result of pts/disease selection. In fact, pts progressing more than 12 mos from the start of NA-based second line appear to have more probabilities to live longer, compared to pts progressing earlier, when they receive another NA-based third line therapy. [Table: see text]

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