Cardiac Biomarkers and Geriatric Assessment in Metastatic Castrate-Resistant Prostate Cancer During Abiraterone Acetate Therapy - A Cardio-Oncology Study.

BACKGROUND: Abiraterone acetate (AA) is a drug used in advanced prostate cancer. However, known clinical factors with predictive and prognostic value are scarce. This study evaluated cardiovascular (CV) factors and geriatric scales as potential markers of superior response during AA therapy. METHODS: This is a prospective observational study. Serum levels of high sensitivity troponin T (hsTnT), D-dimer, NT-proBNP and left ventricle ejection fraction (LVEF) were used for CV evaluation. Questionnaires of G8, VES-13, Activities of Daily Living (ADL), Instrumental Activities of Daily Living (iADL), and Geriatric Depression Scale (GDS) were included in the geriatric screening assessment. All measures were taken before AA initiation. Survival curves and Cox proportional hazard models (univariate and multivariate) were used to determine the predictors for a longer time to treatment failure (TTF). RESULTS: Forty nine patients were included in the study. Overall median TTF was 7.9 months (95% CI: 5.9-12.4). In univariate analysis, factors associated with inferior TTF were (P-value < .05): visceral metastases - HR 2.34; 95% CI: 1.24-4.45, history of coronary artery disease - HR 3.02; 95% CI: 1.19-7.66; LVEF < 50% - HR 2.53; 95% CI: 1.03-6.17; P = .041; age-adjusted D-dimer > upper reference limit (URL) - HR 3.53; 95% CI: 1.81-6.85; P < .001; hsTnT > URL - HR 2.17; 95% CI: 1.13-4.16; P = .016; NT-proBNP ≥ 300 pg/mL - HR 2.3; 95% CI: 1.22-4.34; P = .01; G8 score ≤14 points - HR 2.47; 95% CI: 1.29-4.74; P = .007. In multivariate analysis, age-adjusted D-dimer > URL, G8 score ≤ 14 points and visceral metastases remained statistically significant in prediction of inferior TTF. The number of these factors was associated with shorter median TTF: 0-1 factor - 14.1 months; 2 factors - 5.9 months; 3 factors - 2.7 months; P < .001, log-rank). CONCLUSIONS: Age-adjusted D-dimer, and geriatric G8 scores may predict TTF in men with metastatic castration-resistant prostate cancer during AA therapy. These observations require further study in a larger population.

Cardiovascular comorbidities for prediction of progression-free survival in patients with metastatic renal cell carcinoma treated with sorafenib.

BACKGROUND/AIMS: The purpose of the present study was to determine the relationship between iatrogenic arterial hypertension or baseline cardiovascular comorbidities and outcomes in metastatic renal cell cancer (mRCC) patients treated with sorafenib. METHODS: The study included 148 mRCC patients treated with sorafenib, 63 patients (43%) had preexisting hypertension, 18 patients (12%) coronary artery disease, and 15 patients (10%) mild heart failure. Resting blood pressure (BP) was monitored by clinic and home measurements. Sorafenib-induced hypertension was defined as systolic BP ≥140 and/or diastolic BP ≥90 mm Hg during the first month of treatment. RESULTS: Preexisting cardiovascular comorbidities were not associated with worsening prognosis of patients with mRCC treated with sorafenib. During the first month of treatment, sorafenib-induced hypertension was diagnosed in 76 patients (51.4%), and these patients had a significantly longer PFS (p < 0.00001) and a significantly lower overall mortality risk (p = 0.038). Patients with preexisting and sorafenib-induced hypertension had the longest PFS (p < 0.00001). CONCLUSIONS: Sorafenib-induced hypertension is a positive predictive factor in mRCC patients treated with sorafenib, especially in patients with a history of hypertension.

Angiotensin System Inhibitors May Improve Outcomes of Patients With Castration-Resistant Prostate Cancer During Abiraterone Acetate Treatment-A Cardio-Oncology Study.

BACKGROUND: Abiraterone acetate (ABI) therapy improves overall survival in metastatic prostate cancer (PC) patients; however, this effect may be diminished by concurrent comorbidities. We aimed to evaluate the influence of pre-existing chronic diseases and concomitant medications on the course of ABI treatment among post-chemotherapy patients with metastatic castration-resistant prostate cancer patients (mCRPC). METHODS: From the Polish National Health Fund database, we identified 93 post-chemotherapy, mCRPC patients, who were qualified for ABI treatment in our oncology center between 2014 and 2018. Survival curves and Cox proportional hazard models (univariate and multivariate) were used to determine the predictors for longer time to treatment failure (TTF) of ABI therapy. RESULTS: Median TTF was 9,8 months (IQR: 0,6-56,5) Factors associated with longer TTF were: well controlled hypertension (HR, 0.59; 95% CI. 0.38-0.90; p = 0.02), stable coronary artery disease (HR, 0.56; 95% CI, 0.33-0.95; p=0.03), the use of angiotensin system inhibitor (ASi) (HR, 0.61; 95% CI 0.4-0.94; p = 0,02). Patients who were receiving ASi had median TTF of 12.2 months versus 5.8 months in men who did not receive ASi before ABI initiation. At the start of ABI therapy, the aforementioned groups did not differ in terms of well-known prognostic factors: Gleason score, PSA level, or the number of patients with visceral metastases. In a multivariate analysis, the use of ASi remained statistically significant, even after adjustment for well-known oncological factors (HR, 0.57; 95% CI, 0.34-0.98; p = 0.04). CONCLUSIONS: The use of ASi may enhance and prolong ABI therapy in post-docetaxel mCRPC patients and may potentially be considered a new, non-oncological, predictive factor for longer TTF. This association requires a prospective validation.

Cardiovascular Complications of Prostate Cancer Treatment.

Treatment of prostate cancer (PC) is a rapidly evolving field of pharmacology research. In recent years, numerous novel therapeutics that improve survival and ameliorate disease control have been approved. Currently, the systemic treatment for prostate neoplasm consists of hormonal therapy, chemotherapy, immunotherapy, radiopharmaceuticals, targeted therapy, and supportive agents (e.g., related to bone health). Unfortunately, many of them carry a risk of cardiovascular complications, which occasionally pose a higher mortality threat than cancer itself. This article provides a unique and comprehensive overview of the prevalence and possible mechanisms of cardiovascular toxicities of all PC therapies, including state-of-the-art antineoplastic agents. Additionally, this article summarizes available recommendations regarding screening and prevention of the most common cardiac complications among patients with advanced cancer disease.

Efficacy of targeted therapy in patients with renal cell carcinoma with pre-existing or new bone metastases.

INTRODUCTION: This single-centre retrospective analysis of data from three randomised studies and two expanded-access studies compared the effect of interferon (IFN)-alfa, sunitinib, and sorafenib on the occurrence and progression of metastatic bone lesions in patients with renal cell carcinoma (RCC). METHODS: The analysis included 292 patients: 107 received sunitinib 50 mg/day in 6-week cycles (Schedule 4/2), 147 received sorafenib 800 mg/day, and 38 received placebo or IFN-alfa 9 MU t.i.w. RESULTS: Pre-existing metastatic bone lesions were reported in 82 patients, of which 30 experienced progression. Twenty-three of 210 patients developed new bone lesions. Overall, sunitinib appeared slightly more effective than sorafenib or IFN-alfa at extending mean time to progression of pre-existing bone lesions (P = 0.057). Compared with sorafenib, sunitinib significantly decreased formation (P = 0.034) and prolonged time to occurrence of new bone lesions (P = 0.047). CONCLUSION: Further evaluation of the effect of these therapies on bone metastases in RCC is warranted.