Reply to M.A.N. Şendur et al and J. Michels Penson, David F; Armstrong, Andrew J; Concepcion, Raoul ...
Journal of clinical oncology,
01/2017, Letnik:
35, Številka:
1
Journal Article
Results from a recent survey of 100 urologists and 100 oncologists who treat patients with castration-resistant prostate cancer (CRPC) identified a lack of physician confidence in choosing among the ...variety of new anticancer therapies available, and incorporating these therapies into their clinical decision-making process. In response to a survey conducted by Urologic Oncology, a physician roundtable discussion was convened and this companion summary article created to provide a knowledge-based perspective for optimizing CRPC treatment and improving communication between urologists and oncologists (
http://prostatecancer.urologiconcology.org/
). The participating experts described the importance of a documented testosterone level, despite androgen-deprivation therapy, and an increase in prostate-specific antigen level when diagnosing patients with CRPC. Recently published data and personal clinical experience in CRPC management using approved chemotherapeutics, immunotherapies, and oral agents were discussed, as were management of bone metastases and the overall survival improvement in patients undergoing treatment.
Background: The aim of this study was to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of two distinct formulations of leuprolide acetate (LA); subcutaneous (SC) injection and ...intramuscular (IM) injection. Methods: A total of 32 healthy men were randomized to receive a single 7.5 mg injection of SC-LA ( n = 16) or IM-LA ( n = 16) in this phase I, open-label, parallel-group study. PK was assessed via LA concentrations, and PD via serum luteinizing hormone (LH) and testosterone (T) concentrations. Results: The initial surge of LA was higher for IM-LA than SC-LA (C max 27 ± 4.9 versus 19 ± 8.0 ng/ml, respectively), with a shorter t max (1.0 ± 0.4 versus 2.1 ± 0.8 h). The duration of quantifiable LA concentration was longer for SC-LA (up to 56 versus 42 days for SC-LA and IM-LA, respectively). Median LH concentrations in both groups rapidly increased, followed by gradual decrease. However, SC-LA demonstrated a longer duration of LH suppression, with median levels remaining below 1.0 IU/l through Day 56 compared with IM-LA where LH started to rise by Day 35. Consequently, serum T began to increase by Day 42 in the IM-LA group, with only four subjects maintaining levels ⩽50 ng/dl, compared with 14 subjects in the SC-LA group. By Day 56, 13 SC-LA subjects maintained serum T levels ⩽50 ng/dl. Both SC-LA and IM-LA were well tolerated. Conclusions: Both formulations demonstrated consistent delivery of drug over 1 month; however, SC-LA provided a longer duration of action than expected based on the dosing interval. This profile suggests that SC-LA will provide effective suppression of T over a longer period of time, permitting greater injection scheduling flexibility.
Purpose Nonsteroidal anti-inflammatory drugs such as aspirin prevent cardiovascular disease and several prior studies suggest that nonsteroidal anti-inflammatory drugs also decrease prostate ...inflammation and prostate cancer risk. We investigated the association between nonsteroidal anti-inflammatory drug use, prostate specific antigen and prostate volume, hypothesizing that there would be lower prostate specific antigen and prostate volume with nonsteroidal anti-inflammatory drug use. Materials and Methods The Nashville Men's Health Study uses a multicenter, rapid recruitment protocol to collect clinical, biological, behavioral and body measurement data on 1,277 men older than 40 years who are scheduled for diagnostic prostate biopsy. Nonsteroidal anti-inflammatory drug use was ascertained by survey and clinical interview. Medical charts were reviewed to ascertain current prostate specific antigen, prostate volume and clinical diagnoses following biopsy. Results Approximately 46% of patients reported receiving nonsteroidal anti-inflammatory drugs, primarily aspirin (37%). After adjusting for age, race and other factors prostate volume was similar between aspirin users and nonusers (47.6 vs 46.0 ml, p = 0.16). In contrast, prostate specific antigen was significantly lower in aspirin users (7.3 vs 8.0 ng/ml, p = 0.01). The association between prostate specific antigen and aspirin was significant in men with latent prostate cancer (6.1 vs 7.3 ng/ml, p <0.01), marginal in patients with high grade prostatic intraepithelial neoplasia (5.0 vs 5.9 ng/ml, p = 0.09) and nonsignificant in those with a negative biopsy (5.6 vs 5.7 ng/ml, p = 0.64). The strongest prostate specific antigen-aspirin association was in men with cancer and a prostate volume of 60 ml or more (7.3 vs 12.7 ng/ml, p <0.01). Conclusions Prostate specific antigen was significantly lower in aspirin users with latent cancer. Prostate volume was not associated with nonsteroidal anti-inflammatory drug use. Results suggest that aspirin may affect prostate cancer detection, suggesting a potential detection bias to address in future studies of nonsteroidal anti-inflammatory drugs and prostate cancer prevention.
Objective Prior studies report statins may reduce the risk of advanced prostate cancer. This study investigates the association between statin use and the likelihood of having a PSA or DRE test, ...blood PSA levels, prostate volume, and the severity of lower urinary tract symptoms. We also describe the association between statin use and prostate cancer and high-grade prostatic intraepithelial neoplasia (PIN) before and after controlling for prostate cancer screening indices associated with statin use. Methods The Nashville Men's Health Study used a multicenter, rapid recruitment protocol to collect clinical, biologic, behavioral, and body measurement data from 2,148 men 40 years or older scheduled for diagnostic prostate biopsy. Medication use and other data were ascertained by research survey, clinical interview, and chart review. Results Approximately 37% of participants were taking a statin. Statin use was significantly associated with a 12% lower PSA levels and 8% smaller prostate volume after controlling for age, race, BMI, WHR, aspirin use, and other comorbidity. Simvastatin was more strongly associated with prostate volume, while atorvastatin was associated with PSA. Statin use was marginally associated with increasing PSA test frequency among men with undiagnosed cancer. Statin use was not associated with the frequency or results of digital rectal exams, lower urinary tract symptom severity, high-grade (Gleason > 6) prostate cancer (OR = 0.95 (0.73, 1.24)), low-grade (Gleason = 6) prostate cancer (OR = 1.11 (0.86, 1.42)) or PIN (OR = 0.82, (0.57, 1.17)). Additional control for the number of prior PSA tests, PSA levels, and prostate volume did not alter these results. Conclusion These results suggest selective referral for biopsy associated with statin use is an essential element to address in further understanding the potential for statins to prevent prostate cancer.
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