MicroRNA expression signature of castration-resistant prostate cancer: the microRNA-221/222 cluster functions as a tumour suppressor and disease progression marker

e15195 Background: Abiraterone acetate (AA) plus prednisone (P) has demonstrated an improved survival of patients with castration-resistant prostate cancer (CRPC) compared to placebo plus P in a large phase III trial. In Germany, patients were able to receive AA within a compassionate-use program (CUP). Here, we report the first results of the program. Methods: Patients were eligible for the CUP if they progressed on or after at least one cytotoxic chemotherapy regimens. For CUP entry, patients were considered to have disease progression if they had radiographic evidence of disease progression in soft tissue or bone with or without PSA-progression and ongoing androgen deprivation. Patients received AA 1000mg daily plus prednisone 5mg BID until progression of disease or unacceptable toxicity. Results: Between 02-05/2011, 398 patients were registered for the CUP in Germany. Data from 191/350 (47.9%) of the patients treated at 10 different sites were available for evaluation of efficacy. Median age was 70.72yrs (52.35-87.61) and patients received a median of 1 (1-4) chemotherapy lines prior to CUP entry. Median PSA at baseline was 220.5 ng/ml (0.47-4245); 168 (88%) of patients presented with bone metastasis. With regard to efficacy, 64/191 (33.5%) of the patients showed an unconfirmed PSA-response ≥50%. At a median follow-up of 5.3 months, 51/191 (26.7%) patients had died, resulting in a median PSA-progression free and overall survival of 8.3 and 10.61 months, respectively. In a subset of patients (71/191, 37.2%) data regarding objective response was available with 25/71 (35.2%) achieving an objective response. Data from 114 pts. revealed fatigue (20.3%), hot flushes (15.8%), edema (10.6%), elevated liver enzymes (8.0%) and asthenia (7.9%) being the most frequent toxicities (any grade). Conclusions: Treatment of CRPC patients with AA outside controlled clinical trials leads to considerable PSA- and objective response rates with a favourable toxicity profile, comparable to the results from COU-AA-301 registration trial. Due to the short median follow-up, conclusions regarding PSA-progression free and overall survival may not be drawn.

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Calcium metabolism in patients with castration-resistant prostate cancer: Development of a quantitative urinary assay for extent of bone metastasis.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.130 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 130-130

Author(s):

Ashok P. Pai ◽

Darren Hillegonds ◽

Primo Lara ◽

Chong-xian Pan ◽

David Shelton

Keyword(s):

Prostate Cancer ◽

Bone Metastasis ◽

Bone Turnover ◽

Disease Progression ◽

Calcium Metabolism ◽

Castration Resistant Prostate Cancer ◽

Disease Extent ◽

Castration Resistant ◽

Skeletal Related Events ◽

Bony Metastases

130 Background: In patients with metastatic castration-resistant prostate cancer (CRPC), the degree of perturbation from normal bone turnover provides a strong indication of risk for disease progression, skeletal complications and death. Biomarkers of bone cell function and bone collagen degradation provide an integrated index of the underlying disease for patients with bony metastases, but available bone markers are not precise or accurate. In this study, patients with CRPC with bony metastases will consume a single oral calcium-41 dose and the pharmacokinetics of this will be measured over an 18 month period. Participants will also be assessed clinically for time to progression, skeletal related events and death. Methods: Patients with metastatic castration-resistant prostate cancer and bony metastatses, as diagnosed via bone scintigraphy, who were on bisphosphonates were enrolled into the study. 12 consenting research subjects consumed a single 1.2 microgram 41Ca tracer dose and provided 30-250mL urine specimens (single voids) after dose on day 1 (6h after dosing), days 7, 14, 28, 42, 60, and monthly thereafter. Isotope ratios were measured via accelerator mass spectrometry. Results: Urinary 41Ca/Ca was significantly and inversely associated with increased skeletal tumor burdens suggesting that development of an isotopic urine test for bone metastasis extent is feasible, providing a non-invasive and quantitative measure of disease extent. A calculation of the area under the curve of the measurements between day zero and 14 were inversely correlated with disease extent at baseline. Clinical deterioration with worsening bony disease was associated with a significant decrease in the urinary 41Ca/Ca value. We are currently assessing correlations between bone turnover and outcomes such as therapy effectiveness, disease progression, skeletal related events and death. Conclusions: This work is the first direct measurement of long-term calcium metabolism in advanced prostate cancer, providing a basic scientific complement to cellular and collagen-based measures of bone formation and resorption rates as well as a correlation to clinically relevant outcomes.

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Disease Progression Increases the Risk of Skeletal-Related Events in Patients With Bone Metastases From Castration-Resistant Prostate Cancer, Lung Cancer, or Other Solid Tumors

Cancer Investigation ◽

10.3109/07357907.2010.483508 ◽

2010 ◽

Vol 28 (8) ◽

pp. 849-855 ◽

Cited By ~ 16

Author(s):

N. Simon Tchekmedyian ◽

Yin-Miao Chen ◽

Fred Saad

Keyword(s):

Prostate Cancer ◽

Lung Cancer ◽

Bone Metastases ◽

Disease Progression ◽

Solid Tumors ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Skeletal Related Events

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The IMAAGEN Study: Effect of Abiraterone Acetate and Prednisone on Prostate Specific Antigen and Radiographic Disease Progression in Patients with Nonmetastatic Castration Resistant Prostate Cancer

The Journal of Urology ◽

10.1016/j.juro.2018.03.125 ◽

2018 ◽

Vol 200 (2) ◽

pp. 344-352 ◽

Cited By ~ 24

Author(s):

Charles J. Ryan ◽

E. David Crawford ◽

Neal D. Shore ◽

Willie Underwood ◽

Mary-Ellen Taplin ◽

...

Keyword(s):

Prostate Cancer ◽

Disease Progression ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

Abiraterone Acetate ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Radiographic Disease

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Disease Progression/Clinical Outcome Model for Castration‐Resistant Prostate Cancer in Patients Treated With Eribulin

CPT Pharmacometrics & Systems Pharmacology ◽

10.1002/psp4.49 ◽

2015 ◽

Vol 4 (7) ◽

pp. 386-395 ◽

Cited By ~ 9

Author(s):

JGC van Hasselt ◽

A Gupta ◽

Z Hussein ◽

JH Beijnen ◽

JHM Schellens ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Outcome ◽

Disease Progression ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant

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PSA Nadir and Time to PSA Nadir Following Androgen Deprivation Therapy are the Predictors for Castration-Resistant Prostate Cancer in Patients with Metastatic Prostate Cancer

10.53902/tunr.2021.01.000504 ◽

2021 ◽

Vol 1 (1) ◽

Author(s):

Patranuch Noppakulsatit

Keyword(s):

Prostate Cancer ◽

Disease Progression ◽

Androgen Deprivation Therapy ◽

Specific Antigen ◽

Androgen Deprivation ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Hormone Sensitive ◽

Psa Nadir

Purpose: To evaluate the influence of nadir prostate-specific antigen (PSA) level and time to PSA nadir following androgen deprivation therapy (ADT)on disease progression of castration-resistant prostate cancer (CRPC) in patients with metastatic, hormone-sensitive prostate cancer (mHSPC). Patients and methods: A total of 90 patients with metastatic, hormone-sensitive prostate cancer treated with androgen deprivation therapy in our hospital were included in our retrospective study. Patients’ characteristics, PSA at PADT initiation (initial PSA), PSA nadir, TTN, follow up time, CRPC event were analyzed using Kaplan-Meier analysis and Cox regression model. Results: At a median follow-up of 12 months, 57 patients (63.3%) showed disease progression of CRPC Both PSA nadir and time to PSA nadir (TTN) was independent and significant predictors of CRPC event. Patients with higher PSA nadir (≥0.2ng/dL) and shorter time to PSA nadir (TTN <6 months) had significant shorter time to CRPC. Meanwhile, the Gleason score, age and initial PSA werenot significant predictors of disease progression. In the combined analyses showed patients with higher of PSA nadir and shorter TTN had significantly higher risk for CRPC event compared to lower PSA nadir and longer TTN (HR 69.243, p-value< 0.001) Conclusion: We concluded that both higher PSA nadir and shorter time to PSA nadir are significant predictors of CRPC in patients with metastatic, hormone-sensitive prostate cancer receiving ADT.

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