Correlation between human epidermal growth factor receptor 2 (HER2) status and central nervous system (CNS) involvement in metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 210-210
Author(s):  
Angela Gernone ◽  
Vincenzo Pagliarulo ◽  
Francesco Silvestris ◽  
Arcangelo Pagliarulo
Keyword(s):  
Prostate Cancer ◽  
Median Time ◽  
Performance Status ◽  
Neurological Symptoms ◽  
Her2 Status ◽  
Castration Resistant Prostate Cancer ◽  
Cns Metastases ◽  
Whole Brain ◽  
Increased Risk ◽  
Her 2

210 Background: The incidence of CNS metastasesin prostate cancer is very low. Recent data suggest that HER-2/neu is involved in progression of prostate cancer. Docetaxel-based chemotherapy has provided a survival advantage for mCRPC. The purpose of this retrospective study was to evaluate the relation between HER-2 status and risk of CNS metastases in pts with mCRPC treated with docetaxel. Methods: From 2003 to 2010, 130 pts with mCRPC were treated with 3wk docetaxel 75 mg/mq. 72/130 pts were retreated with the same regimen on disease progression. 50 out of these 72 pts received second docetaxel retreatment. All pts had bone metastases. Pts underwent total body CT scan before starting docetaxel chemotherapy and every 6 months during treatment. The median age was 66 (41–88), median baseline PSA: 110 ng/ml (range 5–1100), median ECOG Performance Status: 1 (range 0–2). The data on 130 pts, who underwent diagnostic biopsy or potentially curative resection , were reviewed. Tissue blocks from primary prostate cancer tissues were obtained. Grade 3 of the HER-2 by IHC staining was defined as a positive result or gene amplification by FISH. 10 out of these 50 pts receiving second docetaxel retreatment were diagnosed with CNS metastases. Results: CNS metastases were observed in HER-2 positive pts. 6/10 pts presented parenchymal metastases: 4 pts were asymptomatic, 3 pts underwent metastasectomy and all of them received palliative whole-brain RT. 4/10 pts presented leptomeningeal metastases with neurological symptoms and 2 of them received palliative whole-brain RT. The median time from prostate cancer diagnosis to the date of diagnosis of CNS metastases was 6 years (1–8). The median time from first cycle of docetaxel to the date of diagnosis of CNS metastases was 3 years (1.5–4). Conclusions: These preliminary data demonstrated that HER-2 expression confers an increased risk of CNS metastases in mCRPC and constitutes a therapeutic challenge. The apparent increase of CNS presentation may be related to the effectiveness of systemic therapy. These informations support the further evaluation of neurological symptoms in long-term docetaxel treated pts.

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.

Pelvic exenteration in patients with nonmetastatic, locally advanced castration-resistant prostate cancer.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 168-168
Author(s):  
Timothy F. Donahue ◽  
Michael J. Morris ◽  
William M. Hilton ◽  
Howard I. Scher ◽  
Bernard H. Bochner
Keyword(s):  
Prostate Cancer ◽  
Median Time ◽  
Pelvic Exenteration ◽  
Performance Status ◽  
Locally Advanced ◽  
Primary Therapy ◽  
Castration Resistant Prostate Cancer ◽  
Symptomatic Disease ◽  
Castration Resistant ◽  
Definitive Therapy

168 Background: A subset of patients who present with localized prostate cancer (PCa) do not develop metastatic disease and recur locally after definitive primary therapy, local salvage therapy, hormones, and systemic intervention. We report our experience in patients with non-metastatic, locally advanced castration resistant prostate cancer (CRPC) treated with radical cystectomy or pelvic exenteration (RC/PEx). Methods: Institutional review board (IRB) approved retrospective review of all patients undergoing RC/PEx for non-metastatic, locally recurrent CRPC after definitive and salvage therapies. Patients were excluded if RC/PEx was for complications of definitive therapy alone. Results: Of 31 patients who had RC/PEx for PCa, 20 met inclusion criteria. Initial therapy was RP (4), XRT (6), brachytherapy (4), brachy/XRT (3), ADT/chemo (2), and ADT alone (1). Five patients had salvage XRT. All received ADT at relapse and 11 had chemotherapy prior to RC/PEx. RC/PEx was performed a median of 8.16 years (0.7 to 24.5) after PCa diagnosis. Patients had pT2b (1), pT3 (5), and pT4 (14) disease at surgery. Lymph nodes were clinically negative in all patients but pathologically positive in six, negative in nine, and not resected in five. Concurrent resections included rectum (12), pelvic wall (6), pubis (1), and iliac vein (1). Eighty five percent of patients had symptoms attributable to locally progressive PCa at RC/PEx including pain, genitourinary or gastrointestinal obstruction and bleeding. All symptomatic patients had relief of disease-related symptoms until recurrence. After a median follow-up of 3.12 years (0.7 to 13.4), nine patients are alive (four have no evidence of disease, five alive with disease), nine dead of disease, and two dead of other causes. Median time to death after RC/PEx was 2.8 years (0.8 to 5.9). For 14 patients who relapsed, metastases developed a median of 398 days (110 to 1,679) after RC/PEx. Ten patients received chemotherapy and 16 had androgen-deprivation therapy after surgery for local recurrence or distant metastases. Median time to chemotherapy after RC/PEx was 346 days (96 to 1,709). Conclusions: For patients with non-metastatic, locally advanced CRPC, RC/PEx to resect symptomatic disease is feasible and appears clinically beneficial. In addition to local control, it may confer significant disease free intervals and relief of symptoms. Even after relapse, performance status was sufficient to undergo systemic therapy.

YB-1 variant and androgen receptor axis-targeted agents in metastatic castration-resistant prostate cancer patients

2020 ◽  
Vol 21 (13) ◽  
pp. 919-928
Author(s):  
Ana Afonso ◽  
Jani Silva ◽  
Ana Rita Lopes ◽  
Sara Coelho ◽  
Ana Sofia Patrão ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Patients ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Allelic Discrimination ◽  
Cox Regression Analysis ◽  
Castration Resistant ◽  
Increased Risk

Aim: To evaluate the influence of YB-1 rs10493112 variant as a genetic marker for response to second-generation androgen receptor axis-target agents. Methods: A hospital-based cohort study of 78 patients with metastatic castration-resistant prostate cancer was conducted. Genotyping was performed by TaqMan® allelic discrimination technology. Main results: In abiraterone-treated and high-risk patients, YB-1 rs10493112 AA genotype carriers showed lower progression-free survival than C allele genotype patients (4 vs 17 months; p = 0.009). For carriers of AA genotype, multivariate Cox regression analysis revealed a fivefold increased risk of progression (p = 0.035). Conclusion: The study findings suggest that, for metastatic and castration-resistant prostate cancer patients, this polymorphism might be a putative marker for the clinical outcome.

scholarly journals Overall Survival of Black and White Men With Metastatic Castration-Resistant Prostate Cancer Treated With Docetaxel

2019 ◽  
Vol 37 (5) ◽  
pp. 403-410 ◽  
Author(s):  
Susan Halabi ◽  
Sandipan Dutta ◽  
Catherine M. Tangen ◽  
Mark Rosenthal ◽  
Daniel P. Petrylak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Black Men ◽  
Performance Status ◽  
Specific Antigen ◽  
White Men ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Black And White ◽  
Castration Resistant

Purpose Several studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist for men with advanced prostate cancer. The primary goal of this analysis was to compare the OS in black and white men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in phase III clinical trials with docetaxel plus prednisone (DP) or a DP-containing regimen. Methods Individual participant data from 8,820 men with mCRPC randomly assigned in nine phase III trials to DP or a DP-containing regimen were combined. Race was based on self-report. The primary end point was OS. The Cox proportional hazards regression model was used to assess the prognostic importance of race (black v white) adjusted for established risk factors common across the trials (age, prostate-specific antigen, performance status, alkaline phosphatase, hemoglobin, and sites of metastases). Results Of 8,820 men, 7,528 (85%) were white, 500 (6%) were black, 424 (5%) were Asian, and 368 (4%) were of unknown race. Black men were younger and had worse performance status, higher testosterone and prostate-specific antigen, and lower hemoglobin than white men. Despite these differences, the median OS was 21.0 months (95% CI, 19.4 to 22.5 months) versus 21.2 months (95% CI, 20.8 to 21.7 months) in black and white men, respectively. The pooled multivariable hazard ratio of 0.81 (95% CI, 0.72 to 0.91) demonstrates that overall, black men have a statistically significant decreased risk of death compared with white men ( P < .001). Conclusion When adjusted for known prognostic factors, we observed a statistically significant increased OS in black versus white men with mCRPC who were enrolled in these clinical trials. The mechanism for these differences is not known.

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.

Survival in metastatic castration resistant prostate cancer (mCRPC) trial participants.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15136-e15136
Author(s):  
Carmel Jo Pezaro ◽  
Aurelius Gabriel Omlin ◽  
Deborah Mukherji ◽  
Diletta Bianchini ◽  
Shahneen Kaur Sandhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Data ◽  
Cox Model ◽  
Performance Status ◽  
Specific Antigen ◽  
Trial Participation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Base Management

e15136 Background: Median overall survival (mOS) in patients (pts) with metastatic prostate cancer progressing despite castrate levels of testosterone (mCRPC) was 13-16 months (m) in the pre-docetaxel era. These data, obtained from clinical trials, were used to construct currently available prognostic nomograms. We hypothesise that these models no longer reflect survival. Pts and physicians urgently require updated prognostic data on which to base management decisions. Methods: Pts with mCRPC treated on phase I-III trials at our institution were identified and data retrospectively collected. Predicted survival by Halabi and Smaletz nomograms were compared to calculated survival using Kaplan-Meier analysis. Cox model multivariate (MV) analysis used variables at referral, including performance status (PS), Gleason (GS), prostate specific antigen (PSA), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), hemoglobin (Hb), visceral disease and albumin. Results: 423 pts with CRPC treated between 2003 and 2011 were included. At diagnosis median age was 62 years (y; 41.8 – 82.7); 226 (53.4%) had metastatic disease. Median interval from diagnosis to CRPC was 2.7y (0.2 – 21.7). At referral 248 pts (58.6%) were chemotherapy-naïve. Halabi and Smaletz models predicted mOS in chemo-naïve pts of 21m and 18m respectively, however the observed mOS was 32m (95%CI 28 – 38). Survival from CRPC was 43m (CI 37 – 46) and 39m (CI 34 - 44) in pre- and post-chemo pts, respectively. Conclusions: Despite aggressive disease characteristics, our pts lived significantly longer than predicted by current nomograms. MV analysis confirmed the importance of several previously identified prognostic factors. Survival data from this large cohort of CRPC pts should encourage men considering clinical trial participation. Previously developed nomograms no longer accurately predict survival.

Results from a phase I study of enzalutamide in combination with docetaxel in men with prostate cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5066-5066
Author(s):  
Mark T. Fleming ◽  
Dana E. Rathkopf ◽  
Jackie Gibbons ◽  
Amy C. Peterson ◽  
Alison Hannah ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Phase I ◽  
Phase I Study ◽  
Performance Status ◽  
Safety Data ◽  
Primary Therapy ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Combination Methods

5066 Background: Enzalutamide (ENZA) is a novel androgen receptor (AR) inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC) who had received prior docetaxel (DOC). DOC also prolongs survival in mCRPC and also appears to have anti-tumor effects mediated through the androgen-receptor axis, providing a compelling rationale for combining the two agents. CYP3A4 plays a role in DOC clearance and is induced by ENZA. We therefore conducted a phase I study to explore the PK and safety profiles of this combination. Methods: This study (NCT01565928) evaluated the safety and pharmacokinetics (PK) of DOC co-administered with ENZA in men with mCRPC on androgen deprivation therapy. Pts received DOC (75 mg/m2) by 1-h infusion every 3 weeks with corticosteroids. ENZA (160 mg/d) was started 24 h after the first DOC infusion. Plasma PK samples were collected for 24 h after Cycle (C) 1 and C2 DOC infusions to enable within-subject comparisons of DOC PK ± ENZA. A sample size of 18 pts able to receive ≥ 2 full doses of DOC was specified for PK analyses. Results: Twenty-two pts were enrolled, 4 did not receive 2 full doses of DOC. As of 21 Sept 2012, preliminary PK and C1 and C2 safety data were available from 15 pts. The median age was 65 (range 46-80 yrs); 11 had ECOG performance status 1 (vs 0). Prior primary therapy included surgery (n=2), radiation (n=4) or both (n=5); median PSA was 44.7ng/mL (1.9-585). ANC<1000/mm3 was reported in 14 pts (1 febrile neutropenia), other adverse events in ≥4 pts included fatigue (11), dyspnea (6), alopecia (5), peripheral neuropathy (5), anemia (4) and dysgueusia (4). No seizures were reported. Preliminary PK data (n=15) show similar DOC exposure (within 20%) for DOC in combination with ENZA vs. DOC alone.Final PK and updated tolerability and efficacy data beyond Cycle 2 will be presented. Conclusions: In mCRPC pts, ENZA does not appear to affect tolerability of DOC or have a clinically meaningful impact on DOC PK. Clinical trial information: NCT01565928.

Enzalutamide in combination with docetaxel in men with prostate cancer (PC): Preliminary results from a phase I study.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 63-63 ◽  
Author(s):  
Mark T. Fleming ◽  
Dana E. Rathkopf ◽  
Jackie Gibbons ◽  
Amy C. Peterson ◽  
Alison Hannah ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Nuclear Translocation ◽  
Performance Status ◽  
Safety Data ◽  
Phase Iii ◽  
Primary Therapy ◽  
Castration Resistant Prostate Cancer ◽  
Current Standard ◽  
Ecog Performance Status ◽  
To Receive

63 Background: Enzalutamide (ENZA), a novel oral androgen receptor (AR) inhibitor, inhibits AR signaling via inhibition of androgen binding to the AR, AR nuclear translocation, and nuclear AR-DNA binding. ENZA demonstrated a survival benefit in men with metastatic castration-resistant prostate cancer (mCRPC) who had received prior docetaxel (Scher et al, NEJM 2012; 367:1187). A Phase III study in men with progressive chemotherapy-naïve disease (PREVAIL), is ongoing. Docetaxel (DOC) is the current standard first-line chemotherapy for mCRPC. CYP3A4, which plays a role in DOC clearance, is induced by ENZA. Patients (pts) eligible to receive DOC may benefit from continued AR inhibition with ENZA, provided the combination is well tolerated with no unacceptable drug-drug interactions. Methods: This study evaluated the safety and pharmacokinetics (PK) of DOC co-administered with ENZA in men with mCRPC on androgen deprivation therapy. Pts received DOC (75 mg/m2) by 1-h infusion every 3 weeks, with corticosteroids. ENZA (160 mg/d) was started 24 h after the first DOC infusion. Plasma PK samples were collected for 24 h after Cycle (C) 1 and C2 DOC infusions to enable within-subject comparisons of DOC PK ± ENZA. A sample size of 18 pts able to receive ≥ 2 full doses of DOC was specified for PK analyses. Results: As of 21 Sept. 2012, 22 pts have been enrolled, 3 did not complete both C1 and C2; PK and C1 and C2 safety data are currently available from 15 pts reported here. The median age was 65 (range 46-80 yrs); 11 had ECOG performance status 1 (vs 0). Prior primary therapy included surgery (n=2), radiation (n=4) or both (n=5); median PSA was 44.7ng/mL (1.9-585). ANC<1000mm3 was reported in 14 pts (1 febrile neutropenia), other adverse events in ≥4 pts included fatigue (11), dyspnea (6), alopecia (5), peripheral neuropathy (5), anemia (4) and dysgueusia (4). No seizures were reported. Preliminary PK data (n=15) show similar DOC exposure (within 20%) for DOC in combination with ENZA vs. DOC alone. Conclusions: This is the first evaluation of ENZA given in combination with DOC.In mCRPC pts ENZA does not appear to affect tolerability of DOC or have a clinically meaningful impact on DOC PK. Clinical trial information: NCT01565928.

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