Kinetics of prostate-specific antigen (PSA) as a marker of abiraterone acetate (AA) efficacy in patients (p) with metastatic castrate-resistant prostate cancer (mCRPC)

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.

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Normalization of Prostate-Specific Antigen and Reduction of Clinical Metastasis Following Zoledronic Acid Treatment in Castrate-Resistant Prostate Cancer

UroToday International Journal ◽

10.3834/uij.1944-5784.2010.02.07 ◽

2010 ◽

Vol 03 (01) ◽

Author(s):

Robert Segal ◽

Fadi Brimo ◽

Wassim Kassouf

Keyword(s):

Prostate Cancer ◽

Zoledronic Acid ◽

Prostate Specific Antigen ◽

Acid Treatment ◽

Specific Antigen ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

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Identification of subgroups of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone plus prednisone at low- vs. high-risk of radiographic progression: An analysis of COU-AA-302

Canadian Urological Association Journal ◽

10.5489/cuaj.5586 ◽

2018 ◽

Vol 13 (6) ◽

Author(s):

Lisa J. Martin ◽

Shabbir M.H. Alibhai ◽

Maria Komisarenko ◽

Narhari Timilshina ◽

Antonio Finelli

Keyword(s):

Prostate Cancer ◽

Radiographic Progression ◽

Proportional Hazards ◽

Specific Antigen ◽

Progression Free Survival ◽

Limited Resource ◽

Abiraterone Acetate ◽

Cox Proportional Hazards ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

Introduction: Radiographic imaging is used to monitor disease progression for men with metastatic castrate-resistant prostate cancer (mCRPC). The optimal frequency of imaging, a costly and limited resource, is not known. Our objective was to identify predictors of radiographic progression to inform the frequency of imaging for men with mCRPC. Methods: We accessed data for men with chemotherapy-naive mCRPC in the abiraterone acetate plus prednisone (AA-P) group of a randomized trial (COU-AA-302) (n=546). We used Cox proportional hazards modelling to identify predictors of time to progression. We divided patients into groups based on the most important predictors and estimated the probability of radiographic progression-free survival (RPFS) at six and 12 months. Results: Baseline disease and change in prostate-specific antigen (PSA) at eight weeks were the strongest determinants of RPFS. The probability of RPFS for men with bone-only disease and a ≥50% fall in PSA was 93% (95% confidence interval [CI] 87–96) at six months and 80% (95% CI 72–86) at 12 months. In contrast, the probability of RPFS for men with bone and soft tissue metastasis and <50% fall in PSA was 55% (95% CI 41–67) at six months and 34% (95% CI 22–47) at 12 months. These findings should be externally validated. Conclusions: Patients with chemotherapy-naive mCRPC treated with first-line AA-P can be divided into groups with significantly different risks of radiographic progression based on a few clinically available variables, suggesting that imaging schedules could be individualized.

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Effects of Abiraterone Acetate on Androgen Signaling in Castrate-Resistant Prostate Cancer in Bone

Journal of Clinical Oncology ◽

10.1200/jco.2010.33.7675 ◽

2012 ◽

Vol 30 (6) ◽

pp. 637-643 ◽

Cited By ~ 131

Author(s):

Eleni Efstathiou ◽

Mark Titus ◽

Dimitra Tsavachidou ◽

Vassiliki Tzelepi ◽

Sijin Wen ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Bone Marrow Aspirate ◽

Specific Antigen ◽

Abiraterone Acetate ◽

Open Label ◽

Clinical Observations ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant ◽

Tumor Expression

Purpose Persistent androgen signaling is implicated in castrate-resistant prostate cancer (CRPC) progression. This study aimed to evaluate androgen signaling in bone marrow–infiltrating cancer and testosterone in blood and bone marrow and to correlate with clinical observations. Patients and Methods This was an open-label, observational study of 57 patients with bone-metastatic CRPC who underwent transiliac bone marrow biopsy between October 2007 and March 2010. Patients received oral abiraterone acetate (1 g) once daily and prednisone (5 mg) twice daily. Androgen receptor (AR) and CYP17 expression were assessed by immunohistochemistry, testosterone concentration by mass spectrometry, AR copy number by polymerase chain reaction, and TMPRSS2-ERG status by fluorescent in situ hybridization in available tissues. Results Median overall survival was 555 days (95% CI, 440 to 965+ days). Maximal prostate-specific antigen decline ≥ 50% occurred in 28 (50%) of 56 patients. Homogeneous, intense nuclear expression of AR, combined with ≥ 10% CYP17 tumor expression, was correlated with longer time to treatment discontinuation (> 4 months) in 25 patients with tumor-infiltrated bone marrow samples. Pretreatment CYP17 tumor expression ≥ 10% was correlated with increased bone marrow aspirate testosterone. Blood and bone marrow aspirate testosterone concentrations declined to less than picograms-per-milliliter levels and remained suppressed at progression. Conclusion The observed pretreatment androgen-signaling signature is consistent with persistent androgen signaling in CRPC bone metastases. This is the first evidence that abiraterone acetate achieves sustained suppression of testosterone in both blood and bone marrow aspirate to less than picograms-per-milliliter levels. Potential admixture of blood with bone marrow aspirate limits our ability to determine the origin of measured testosterone.

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MP34-09 IMPACT OF PROSTATE SPECIFIC ANTIGEN DOUBLING TIME ON METASTASIS AND INCREASED COSTS ASSOCIATED WITH PROGRESSION TO METASTATIC CASTRATE-RESISTANT PROSTATE CANCER

The Journal of Urology ◽

10.1097/01.ju.0000555905.24567.4e ◽

2019 ◽

Vol 201 (Supplement 4) ◽

Author(s):

Stephen J. Freedland ◽

Krishnan Ramaswamy* ◽

Stanislav Lechpammer ◽

Jack Mardekian ◽

Neil M. Schultz ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Doubling Time ◽

Specific Antigen ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

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A castrate-resistant metastatic prostate cancer patient with severe pancytopenia, successfully treated with docetaxel chemotherapy

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155219890653 ◽

2019 ◽

Vol 26 (5) ◽

pp. 1254-1258

Author(s):

Anuradha Kunthur

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Prostate Specific Antigen ◽

Bone Marrow Involvement ◽

Specific Antigen ◽

Docetaxel Treatment ◽

Castrate Resistant Prostate Cancer ◽

Severe Pancytopenia ◽

Castrate Resistant ◽

Docetaxel Chemotherapy

Introduction Prognosis of metastatic castrate-resistant prostate cancer is poor with a median survival of 12 to 36 months. Bone metastasis is common, and bone marrow metastasis occurs later in the disease course. The median survival in these patients after bone marrow involvement is less than six months. We report a case of castrate-resistant prostate cancer patient presented with severe pancytopenia due to bone marrow involvement of prostate cancer, treated successfully with docetaxel chemotherapy. Post chemotherapy, the patient became transfusion independent and prostate-specific antigen improved to 0.1 ng/ml from 1051 ng/ml. Case report A 70-year-old gentleman with a history of metastatic prostate cancer on androgen deprivation therapy and polycythemia vera presented to emergency room with dizziness and melena. Workup revealed severe pancytopenia with platelet count of 12k and hemoglobin of 4.5 gm/dl. Bone marrow biopsy confirmed diffuse involvement of bone marrow with prostate cancer. Prostate-specific antigen was 1051 gm/dl. Management and outcome: The patient received 14 units of packed red blood cell, 10 units of platelet transfusion within one week. Docetaxel chemotherapy was started along with thrombopoietin agonist romiplostim and pegylated filgrastim. He received five cycles of docetaxel treatment. Post chemotherapy, the patient became transfusion independent and prostate-specific antigen improved to 1.17 ng/ml from 1051 ng/ml. The patient is still alive one year after the presentation with good quality of life and the prostate-specific antigen further improved to 0.1 ng/dl. Conclusion This case suggests that selected patients with severe pancytopenia, due to bone marrow infiltration of prostate cancer, can be treated with docetaxel chemotherapy and romiplostim support with significant response. Docetaxel treatment may be beneficial to unpack the marrow and for quicker response in patients with good performance status.

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Emerging Treatments for Castrate-Resistant Prostate Cancer

Journal of Pharmacy Practice ◽

10.1177/0897190010397718 ◽

2011 ◽

Vol 24 (4) ◽

pp. 366-373

Author(s):

Michell B. Redding ◽

Minal Surati

Keyword(s):

Prostate Cancer ◽

Antitumor Agents ◽

Specific Antigen ◽

Abiraterone Acetate ◽

Cytotoxic Agents ◽

Emerging Treatments ◽

Castrate Resistant Prostate Cancer ◽

New Treatment ◽

Castrate Resistant ◽

Androgen Depletion

Castrate-resistant prostate cancer (CRPC) is a challenging aspect in the treatment of prostate cancer. Research has identified several pathways in the pathogenesis of CRPC. Several new agents targeting some of these pathways have shown promising data during clinical trials. In the area of androgen depletion, abiraterone acetate and MDV100 have been studied and have shown to decrease prostate-specific antigen (PSA) levels in phase I and II studies. Bevacizumab is a monoclonal antibody antiangiogenesis agent that targets vascular endothelial growth factor (VEGF) and has shown to decrease PSA levels in combination with other cytotoxic agents. Three agents, ixabepilone, patupilone, and sagopilone, in the class of epothilones (tubulin polymerizing antitumor agents), have shown moderate reductions in PSA levels and moderate adverse effects. The results of ongoing studies with these new treatment agents may offer viable alternatives to the traditional treatment of CRPC to decrease disease progression and improve overall survival.

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