scholarly journals Abiraterone versus bicalutamide in combination with gonadotropin releasing hormone antagonist therapy for high risk metastatic hormone sensitive prostate cancer.

2021 ◽  
Author(s):  
Takashi Ueda ◽  
Takumi Shiraishi ◽  
Saya Ueda ◽  
Motoharu Ohashi ◽  
Toru Matsugasumi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Progression Free Survival ◽  
Gonadotropin Releasing Hormone ◽  
Free Survival ◽  
Releasing Hormone ◽  
Group A ◽  
Psa Progression ◽  
Hormone Sensitive ◽  
Group B

Abstract ObjectivesTo compare the efficacy of abiraterone with that of bicalutamide in combination with gonadotropin-releasing hormone antagonist treatment for high risk metastatic hormone-sensitive prostate cancer patients.MethodsOne hundred and forty-nine patients with high risk metastatic hormone-sensitive prostate cancer at our hospital and affiliated hospitals between December 2013 and July 2020 were retrospectively identified. Fifty patients were administered abiraterone (1000mg/day) plus prednisolone (5mg/day) with gonadotropin-releasing hormone antagonist (degarelix) (group A) and 99 patients were administered bicalutamide (80mg/day) with gonadotropin-releasing hormone antagonist (group B). ResultsPSA- progression-free survival of group A was significantly longer than that of group B. Abiraterone therapy and Gleason score were significant independent factors for PSA-progression-free survival. By propensity score matching, total 56 matched patients were obtained. PSA-PFS (p<0.001) and OS (p=0.0071) of high risk mHNPC patients were significantly longer in abiraterone group of matched patients. Abiraterone therapy and Gleason score were still shown to be significant independent factors for PSA-PFS in matched patients.ConclusionsPSA-progression-free survival and overall survival in patients who were treated with abiraterone in combination with gonadotropin releasing hormone antagonist were significantly better than those of bicalutamide.

scholarly journals Abiraterone acetate versus bicalutamide in combination with gonadotropin releasing hormone antagonist therapy for high risk metastatic hormone sensitive prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takashi Ueda ◽  
Takumi Shiraishi ◽  
Saya Ito ◽  
Munehiro Ohashi ◽  
Toru Matsugasumi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Gleason Score ◽  
Gnrh Antagonist ◽  
Abiraterone Acetate ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Group A ◽  
Hormone Sensitive ◽  
Group B

AbstractThe objective of this study was to compare the efficacy of abiraterone acetate with that of bicalutamide in combination with gonadotropin-releasing hormone (GnRH) antagonist treatment for patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). A total of 149 patients with mHSPC who underwent treatment at our hospital and affiliated hospitals between December 2013 and July 2020 were retrospectively identified. Fifty patients were administered abiraterone acetate (1000 mg/day) plus prednisolone (5 mg/day) with a GnRH antagonist (degarelix) (group A), and 99 patients were administered bicalutamide (80 mg/day) with a GnRH antagonist (group B). The prostate-specific antigen (PSA) progression-free survival (PSA-PFS) was significantly longer in group A than in group B. Abiraterone acetate therapy and Gleason score were significant independent factors of PSA-PFS. Using propensity score matching, 56 matched patients were obtained. The PSA-PFS (p < 0.001) and overall survival (OS) (p = 0.0071) of patients with high-risk mHSPC were significantly longer in group A of matched patients. Abiraterone acetate therapy and Gleason score were significant independent factors for PSA-PFS in matched patients. The PSA-PFS and OS of patients treated with abiraterone acetate in combination with a GnRH antagonist were significantly better than those treated with bicalutamide.

Interim results from a phase 2 study of olaparib (without ADT) in men with biochemically-recurrent prostate cancer after prostatectomy, with integrated biomarker analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5045-5045 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Hao Wang ◽  
Benjamin A. Teply ◽  
William Kevin Kelly ◽  
Jamie Willms ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adaptive Design ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Parp Inhibition ◽  
Free Survival ◽  
Second Stage ◽  
Biomarker Analysis ◽  
Psa Progression ◽  
Hormone Sensitive

5045 Background: Pts with biochemically-recurrent (BCR) prostate cancer after local therapy with a PSA doubling time (PSADT) of ≤6 mo are likely to develop metastases and death from their disease. We hypothesized that the PARP inhibitor olaparib would be effective as a non-hormonal therapy for biomarker-unselected pts with BCR after prostatectomy, the first study of PARP inhibition in the hormone-sensitive setting. We report pre-specified interim results from the first stage of the trial. Methods: This investigator-initiated multicenter study (NCT03047135) enrolled pts with non-metastatic BCR after prostatectomy, with a PSADT of ≤6 mo. PSA had to be ≥1.0 ng/mL, with T ≥150 ng/dL. Pts received olaparib 300 mg twice daily (without ADT), until a doubling of their PSA or metastatic progression. The primary endpoint was confirmed ≥50% PSA decline (PSA50 response). Secondary endpoints included safety, minor PSA response (1-50% reduction), and PSA progression-free survival. Integrated biomarker analyses included somatic DNA sequencing, RNA expression analysis and IHC for DNA damage markers, using prostatectomy specimens. The study was designed to enroll a biomarker-unselected population using a staged-adaptive design, with up to 50 pts. In the first stage, ≥3 PSA50 responses out of 20 pts were required to proceed to the second stage; otherwise enrichment with biomarker-selected pts would occur. Results: Between 5/2017 and 11/2018, 20 men (median age, 65) enrolled in the first stage, with a median follow-up of 6 (range, 3-16) mo. Median PSADT was 3.1 mo, and 55% had Gleason ≥8 cancers. Seven men (35%) had BRCA2/ATM mutations. Three men (15%) had PSA50 responses (all had BRCA2 muts – 2 had complete PSA responses), and 4 other men (20%) had minor PSA responses. Median PSA progression-free survival was greater in men with vs. without BRCA2/ATM muts (9 vs. 4 mo; P= 0.02). Common toxicities of olaparib included fatigue, nausea, anemia and leukopenia; 2 men required a dose reduction. Conclusions: Olaparib (without ADT) was tolerable and showed activity in hormone-sensitive BCR prostate cancer, especially in men with BRCA2 muts. Second-stage enrolment is ongoing. Clinical trial information: NCT03047135.

Randomised phase 3 trial of enzalutamide in androgen deprivation therapy (ADT) with radiation therapy for high risk, clinically localized prostate cancer: ENZARAD (ANZUP 1303).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS156-TPS156
Author(s):  
Scott Williams ◽  
Ian D. Davis ◽  
Christopher Sweeney ◽  
Martin R. Stockler ◽  
Andrew James Martin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Open Label ◽  
Phase 3 ◽  
Free Survival ◽  
Castration Resistant ◽  
Psa Progression

TPS156 Background: Adjuvant ADT with an LHRH analog (LHRHA) given before, during and after radiotherapy (RT) is standard of care for high risk localised prostate cancer (PC). Enzalutamide improves overall survival (OS) in castration-resistant, metastatic prostate cancer. We hypothesized that the addition of enzalutamide to adjuvant ADT and RT will improve outcomes. The aim is to determine the effects of enzalutamide versus a conventional non-steroidal anti-androgen (NSAA) as part of neoadjuvant and adjuvant ADT in men undergoing RT for high risk, localized PC. Methods: DESIGN: Open label, randomised, phase 3 trial including ANZ, USA, UK, Ireland and Europe. ENDPOINTS: OS (primary), cause-specific survival, PSA progression free survival (PFS), clinical PFS, time to subsequent hormonal therapy, time to castration-resistant disease (PCWG2 criteria), metastasis free survival (MFS), adverse events and health-related quality of life (HRQOL). CORRELATIVE OBJECTIVES: identification of prognostic/predictive biomarkers from archival tumour tissue and serial blood samples. SAMPLE SIZE: 800 participants with a minimum follow-up of 5.5 yrs is designed to give 80% power to detect 33% reduction in the hazard of death assuming 5-year survival rate of 76% amongst controls. TREATMENT: Enzalutamide 160mg daily for 24 months versus conventional NSAA for 6 months. All participants receive LHRHA for 24 months, and RT starting about week 16 delivered as 78Gy in 39#, or 46Gy in 23# plus brachytherapy (nodal RT optional for N0, mandatory for N1). ASSESSMENTS: Baseline, then every 8 weeks until year 2, then 3-4 monthly until year 5, 6-monthly until year 7, then annually. Imaging with CT/MRI and bone scan at baseline, PSA progression, then 6 monthly until re-initiation of ADT, when PCWG2 criteria for CRPC are met and then 3 monthly until evidence of metastases. 623 participants recruited from 61 sites as of 16 October 2017. ENZARAD is an investigator-initiated cooperative group trial led by ANZUP Cancer Trials Group with funds and product from Astellas. Clinical trial information: NCT02446444.

scholarly journals Chromogranin A predicts outcome in prostate cancer patients treated with abiraterone

2014 ◽  
Vol 21 (3) ◽  
pp. 487-493 ◽  
Author(s):  
Salvatore Luca Burgio ◽  
Vincenza Conteduca ◽  
Cecilia Menna ◽  
Elisa Carretta ◽  
Lorena Rossi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chromogranin A ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Psa Response ◽  
Group A ◽  
Group 3 ◽  
Group B

In this retrospective study, we evaluated the chromogranin A (CgA) baseline value as a predictor of clinical outcome in patients with metastatic castration-resistant prostate cancer (CRPC) treated with abiraterone 1000 mg per day, whose disease progressed after docetaxel chemotherapy. In the 48 evaluable patients, serum CgA level was normal when <120 ng/ml (group A, n=16), within three times the upper normal value (UNV) when between 120 and 360 (group B, n=16), more than three times the UNV when ≥360 ng/ml (group C, n=16). Decline in PSA level ≥50% or more (PSA RR) was observed in 26 of 48 (54%) patients. PSA response rate did not correlate with the CgA groups. CgA levels more than three times the UNV predicted an early radiological progressive disease in eight of 11 cases (73%). The median progression-free survival (PFS) among the CgA groups A, B, and C was 9.2, 9.2, and 4.8 months respectively, P=0.0459. The median overall survival (OS) among the CgA groups was 19.0, 18.8, and 10.8 months respectively, P=0.2092. In the multivariate analysis, PSA RR (nonresponsive vs responsive) and CgA levels (group 3 vs groups 1+2) were predictors of PFS (P=0.0002 and P=0.0047 respectively), whereas PSA RR only was significantly associated with OS (P=0.0024), while CgA levels remained of borderline significance (P=0.0919). A serum CGA level more than three times the UNV predicted PFS and showed a trend vs OS prediction, independently from PSA response, in CRPC patients treated with abiraterone.

Thalidomide Based Regimens (TBR) for Relapsed/Refractory Multiple Myeloma Patients: Long Term Follow Up, Unmaintained Remissions and Disease Control after Subsequent Treatments.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4812-4812
Author(s):  
Maria Roussou ◽  
Efstathios Kastritis ◽  
Athanasios Anagnostopoulos ◽  
Evangelos Eleftherakis-Papaiakovou ◽  
Charis Matsouka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Long Term Follow Up ◽  
Group A ◽  
Pulse Dexamethasone ◽  
Group B

Abstract Introduction: The effectiveness of thalidomide based regimens (TBR) in patients with relapsed/refractory multiple myeloma is well established. However, there are still limited data regarding the long term follow up after such regimens and the outcome of patients when they progress and they receive further treatment. In order to answer these questions we evaluated a series of 114 patients with relapsed/refractory multiple myeloma who were treated with TBR. None of these patients had previously received thalidomide, bortezomib or lenalidomide. Patients and Methods: All patients were treated with thalidomide and dexamethasone with or without other oral agents. More specifically 41 patients had received continuous thalidomide and pulse dexamethasone, 25 patients clarithromycin, continuous thalidomide and pulse dexamethasone, 43 patients intermittent thalidomide, pulse dexamethasone and cyclophosphamide and 5 patients continuous thalidomide, pulse dexamethasone and cyclophosphamide. Type of treatment at the time of progression after TBR, response to this treatment and progression free survival were recorded for each patient. Moreover, patients who received novel agents after progression to TBR, were divided into 2 subgroups, according to their resistance to thalidomide. In group A, patients had refractory or progressive myeloma while on TBR or within 2 months after discontinuation of TBR. In group B, myeloma progressed more than 2 months after discontinuation of TBR. Results: Among the 114 patients, 41 had not responded to TBR and 73 (64%) had achieved at least a partial response. The median PFS for all patients was 8 months. As of June 2007, 10 patients remain without progression from 28 to 81 months (median 54 months). Eight patients remain off treatment and without progression for a median of 56 months (range 28–81). Patients who did not respond to or progressed after TBR were analyzed for further treatment and outcome. Thirty eight patients (37%) died before receiving further treatment, 23 patients (23%) received conventional chemotherapy and 41 patients (40%) received continuous thalidomide and dexamethasone +/− clarithromycin or cyclophosphamide (17 patients), bortezomib and dexamethasone (7 patients), melphalan-bortezomib-dexamethasone and intermittent thalidomide (12 patients) or lenalidomide with dexamethasone (5 patients). Among these 41 patients, 24 were classified in group A (thalidomide resistant) and 17 in group B. Overall 17 (41%) achieved at least partial response after retreatment with novel agent-based regimens. A response was observed in 46% of patients in group A and in 35% of patients in group B. The median progression free survival of the 41 patients who received retreatment with novel agents was 9.2 months and the median survival was 17 months. Among the 23 patients who received conventional chemotherapy only five (21%) patients responded and the progression free survival and the median survival were 5.3 and 10.2 months, respectively. Conclusions: After an oral TBR regimen 6 (5%) patients remain without treatment and free of progression for more than 4 years. A significant number of patients who progressed after TBR and who received further treatment which included a novel agent achieved a response, including several patients who were resistant to TBR.

Treatments for metastatic hormone-sensitive prostate cancer: A systematic review.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 346-346
Author(s):  
Belal Firwana ◽  
Mohamad Bassam Sonbol ◽  
Fade A. Mahmoud ◽  
Konstantinos Arnaoutakis
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
P Value ◽  
Free Survival ◽  
Appropriate Treatment ◽  
Individual Trial ◽  
Efficacy Outcome ◽  
Significant Difference ◽  
Hormone Sensitive

346 Background: Over the past few years, the treatment of metastatic hormone sensitive prostate cancer (mHSPC) was revolutionized with the addition of docetaxel (DOC) or abiraterone (ABI) to the previous standard of care androgen deprivation treatment (ADT). Here, we sought to compare the effectiveness of docetaxel and abiraterone directly against ADT and indirectly to each other. Methods: We included randomized controlled trials (RCT) evaluating the efficacy of treatments in adults with newly diagnosed mHSPC. First-line treatments with DOC and ABI were considered. Efficacy outcome measures are overall survival (OS) and failure-free survival as (FFS) as defined by individual trial. If FFS was not reported, biochemical progression-free survival was considered FFS due to its specificity. The overall effect was pooled using the DerSimonian random effects model. Testing for subgroup difference was conducted using meta-regression method. Results: A total of five RCTs were included; three RCTs compared DOC+ADT versus ADT involving 2,992 participants, and two RCT compared ABI+ADT versus ADT involving 2,201 participants. The addition of DOC to ADT showed a significant improvement in OS compared to ADT monotherapy (HR 0.77, 95% CI 0.66 to 0.89) as well did the addition of ABI to ADT (HR 0.62, 95% CI 0.53 to 0.71). p-value for subgroup interaction was <0.05, suggesting a significant difference between pooled DOC and ABI effects, favoring the addition of ABI vs. DOC to ADT. Similar effects were found in significantly improving FFS when adding DOC (HR 0.64, 95% CI 0.58 to 0.70) or ABI (HR 0.30, 95% CI 0.27 to 0.34) to ADT compared to ADT monotherapy. p-value for interaction subgroup interaction was again significant <0.05 favoring the addition of ABI vs. DOC to ADT. Conclusions: The addition of either DOC or ABI to ADT showed significant improvement in OS and FFS when compared to ADT monotherapy in patients with mHSPC. Test for interaction suggests better outcome of ABI in comparison against DOC. Discussion with patients is encouraged to choose the appropriate treatment considering the adverse event profile for each. Further head-to-head comparison is needed to determine the effect.

The effect of AKR1C3 on the switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients receiving abiraterone.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 133-133
Author(s):  
Yuchao Ni ◽  
Jinge Zhao ◽  
Junru Chen ◽  
Guangxi Sun ◽  
Sha Zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Psa Progression ◽  
Biochemical Progression ◽  
First Line Treatment

133 Background: Abiraterone is the first-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC) and is recommended to be used with prednisone. Previous studies had demonstrated that the switch from prednisone to dexamethasone in some mCRPC patients can reverse abiraterone-resistance. However, it remains uncertain which group of patients will benefit from such switching. AKR1C3 is a critical enzyme contributing to the drug-resistance of abiraterone. Here, we aim to explore the significance of AKR1C3 in predicting the therapeutic efficacy of the corticosteroid switching in mCRPC patients receiving abiraterone. Methods: In total, 43 PCa patients treated with abiraterone after mCRPC between 2016 and 2018 in our institution were included. After biochemical progression in abiraterone plus prednisone, all cases received a corticosteroid switch to abiraterone plus dexamethasone. The expression of AKR1C3 was detected by immunohistochemical staining from re-biopsy (re‐Bx) of primary prostate lesions at the time of mCRPC. Kaplan‐Meier curves were used to analyze the association between AKR1C3 and treatment outcomes. Results: Totally, AKR1C3 was positive in 19 of 43 (44.19%) cases. In the corticosteroid switch treatment, 30% PSA decline was confirmed in 18/43 (41.86%) patients, while the median PSA progression‐free survival (PSA-PFS) and overall survival (OS) was 4.93 Mo and 31.57 Mo, respectively in the whole cohort. AKR1C3 expression was associated with statistically shorter median PSA-PFS (4.50 Mo vs 7.73 Mo; p =0.010) and numerically lower median OS (25.43 Mo vs 39.37 Mo, p =0.274). While the 30% PSA decline rate was numerically comparable between those with and without AKR1C3 expression (31.6% vs 50.0%, p =0.224). Conclusions: This study showed AKR1C3 detection in tissues from prostate re‐Bx at mCRPC was associated with poor PSA-PFS in the corticosteroid switch from abiraterone plus prednisone to abiraterone plus dexamethasone. These results would be helpful in making optimal personalized treatment decisions for patients with mCRPC, facilitating physicians predicting the effectiveness of corticosteroid switch treatment.

Carboplatin-Paclitaxel Versus Cisplatin-Ifosfamide in the Treatment of Uterine Carcinosarcoma: A Retrospective Cohort Study

2014 ◽  
Vol 24 (7) ◽  
pp. 1256-1261 ◽  
Author(s):  
Domenica Lorusso ◽  
Fabio Martinelli ◽  
Maria Mancini ◽  
Italo Sarno ◽  
Antonino Ditto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Oncologic Outcomes ◽  
Uterine Carcinosarcoma ◽  
Suitable Alternative ◽  
Free Survival ◽  
Gynecology And Obstetrics ◽  
Group A ◽  
Group B

ObjectiveUterine carcinosarcoma (CS) is a rare neoplasm whose adjuvant treatment has not been yet defined. We report on the activity and toxicity of cisplatin-ifosfamide and carboplatin-paclitaxel as adjuvant treatments for patients with uterine CS.MethodsData of International Federation of Gynecology and Obstetrics (FIGO) stage I to IV uterine CS patients treated between 2006 and 2012 with adjuvant chemotherapy (cisplatin 20 mg/mq and ifosfamide 1500 mg/mq day 1 to 4 every 3 weeks plus prophylactic Granulocyte colony-stimulating factor (G-CSF) support [group A] or carboplatin area under the curve -5 (AUC-5) and paclitaxel 175 mg/mq d1q21 [group B]) were retrospectively reviewed. Progression-free survival, overall survival, and chemotherapy-related toxicities were compared between the 2 groups. A subanalysis of oncologic outcomes according to the sarcomatous component (homologous vs heterologous) was performed.ResultsForty-six women were evaluated—21 in group A and 25 in group B. At a median follow-up of 30 months, the median progression-free survival was 11.6 months (95% confidence interval [CI], 6.3–16.9) and 16.6 months (95% CI, 14.7–18.5) for group A and B, respectively (P= 0.20). The median overall survival was 17.1 months (95% CI, 12.6–21.5) and 35.1 months (95% CI, 26.3–43.7) for group A and B, respectively (P= 0.14). No differences were identified among heterologous or homologous components according to chemotherapy treatment. Toxicity profiles widely differ between treatment arms.ConclusionsBecause of the super imposable activity and the better toxicity profile, carboplatin-paclitaxel may be a suitable alternative to cisplatin-ifosfamide in the treatment of uterine CS.

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