The objective of this study was to conduct an indirect treatment comparison between cabazitaxel, abiraterone and enzalutamide to determine the clinical efficacy and safety of cabazitaxel relative to comparators in the treatment of patients with metastatic castrate-resistant prostate cancer who progress on docetaxel-based therapies.
A systematic literature review was conducted to inform the network meta-analysis of cabazitaxel, abiraterone and enzalutamide. Due to a lack of head-to-head trials, studies with a comparator arm of best supportive care were included in the analysis. Overall survival, progression-free survival, and adverse events were compared within both Bayesian and Frequentist frameworks. The ratios for survival outcomes were estimated using hazard ratios (HR), and the ratios for adverse events between groups were estimated using odds ratios (ORs); uncertainty was reported as 95% confidence (Frequentist) and credible (Baysesian) Intervals.
Three of thirteen trials identified for abstraction were relevant for analyses. Median overall survival was not statistically significantly different for abiraterone (HR = 1.04; 95% CI = 0.83-1.28) or enzalutamide (HR = 0.88; 95% CI = 0.69-1.11) when compared to cabazitaxel in the Bayesian analysis. Anaemia (OR = 3.71; 95% CI = 1.01-10.44), diarrhoea (OR = 16.60; 95% CI = 1.41-75.31) and haematuria (OR = 3.88; 95% […]
In recent pooled analyses among whites and Asians, mortality was shown to rise markedly with increasing body mass index (BMI; weight (kg)/height (m)(2)), but much less is known about this association among blacks. This study prospectively examined all-cause mortality in relation to BMI among 22,014 black males, 9,343 white males, 30,810 black females, and 14,447 white females, aged 40-79 years, from the Southern Community Cohort Study, an epidemiologic cohort of largely low-income participants in 12 southeastern US states. Participants enrolled in the cohort from 2002 to 2009 and were followed up to 8.9 years. Hazard ratios and 95% confidence intervals for mortality were obtained from sex- and race-stratified Cox proportional hazards models in association with BMI at cohort entry, adjusting for age, education, income, cigarette smoking, and alcohol consumption. Elevated BMI was associated with increased mortality among whites (hazard ratios for BMI >40 vs. 20-24.9 = 1.37 (95% confidence interval (CI): 1.02, 1.84) and 1.47 (95% CI: 1.15, 1.89) for white males and white females, respectively) but not significantly among blacks (hazard ratios = 1.13 (95% CI: 0.89, 1.43) and 0.87 (95% CI: 0.72, 1.04) for black males and black females, respectively). In this large cohort, obesity in mid-to-late adulthood […]
Adiponectin is a promising biomarker linking obesity and disease risk; however, limited data are available regarding adiponectin in black women among whom obesity is highly prevalent. A cross-sectional analysis was conducted to assess racial differences and correlates of serum adiponectin measured in 996 black and 996 white women enrolled in the Southern Community Cohort Study through Community Health Centers in 12 southeastern states from 2002 to 2006. Black subjects had significantly lower adiponectin levels than white subjects (median 10.9 vs 14.9 μg/mL, Wilcoxon p < .0001). Among black subjects, adiponectin was lower among overweight and obese women compared with healthy weight women but showed no clear decreasing trend with increasing severity of obesity; adjusted geometric means (95% confidence interval) were 15.0 [13.8-16.4], 11.5 [10.6-12.5], 9.7 [9.0-10.6], 11.4 [10.3-12.6], and 10.9 [9.5-12.6] μg/mL for body mass index [BMI] categories of 18.5-24.9, 25-29.9, 30-34.9, 35-39.9, and 40-45, p for trend <.0001). In contrast, among whites there was a monotonic reduction in adiponectin over increasing BMI (adjusted geometric means = 19.9 [18.3-21.7], 15.1 [13.9-16.4], 14.3 [13.2-15.5], 12.5 [11.2-13.9], and 11.0 [9.7-12.5] μg/mL, p for trend <.0001). BMI, age, high-density lipoprotein cholesterol, and hypertension were important correlates of adiponectin in both groups. Among women, […]
The side-effects associated with androgen deprivation therapy (ADT) include weight gain, dyslipidemia, and insulin resistance. As cataracts have been linked to these metabolic abnormalities, an increased risk of cataract may be another adverse consequence of ADT use.
Using data from the Surveillance, Epidemiology and End Results-Medicare database, we estimated risk of cataract associated with ADT among 65,852 prostate-cancer patients. ADT treatment was defined as at least one dose of a gonadotropin-releasing hormone agonist or orchiectomy within 6 months after prostate cancer diagnosis. The outcome measure was a first claim of cataract diagnosis identified in Medicare claim files. Cox regression was used to estimate hazard ratios (HR) for the effects of ADT treatment, controlling for confounders.
Gonadotropin-releasing hormone agonist use was associated with a modest increase in cataract incidence (HR 1.09, 95% confidence interval 1.06-1.12). Orchiectomy was also associated with an increased risk of cataract among men with no history of cataract prior to prostate cancer diagnosis (HR 1.26, 95% confidence interval 1.07-1.47).
In the first systematic investigation of the association between ADT and cataract, our results suggest an elevation in theincidence of cataract among ADT users. Further study, preferably prospective in design, is needed to provide additional evidence to support or refute these findings.
Beebe-Dimmer J, Morgenstern H, Cetin K, Yee C, Bartoces M, Shahinian V, Fryzek J, Acquavella J, Schwartz KA. Androgen deprivation therapy […]
Venous thromboembolism (VTE) frequently complicates cancer. Data on tumour-specific VTE predictors are limited, but may inform strategies to prevent thrombosis.
We computed incidence rates (IRs) with 95% confidence intervals (CIs) for VTE hospitalisation in a cohort of cancer patients (n=57,591) and in a comparison general-population cohort (n=287,476) in Denmark. The subjects entered the study in 1997-2005, and the follow-up continued through 2006. Using Cox proportional-hazards regression, we estimated relative risks (RRs) for VTE predictors, while adjusting for comorbidity.
Throughout the follow-up, VTE IR was higher among the cancer patients (IR=8.0, 95% CI=7.6-8.5) than the general population (IR=4.7, 95% CI=4.3-5.1), particularly in the first year after cancer diagnosis (IR=15.0, 95% CI=13.8-16.2, vs IR=8.6, 95% CI=7.6-9.9). Incidence rates of VTE were highest in patients with pancreas (IR=40.9, 95% CI=29.5-56.7), brain (IR=17.7, 95% CI=11.3-27.8) or liver (IR=20.4, 95% CI=9.2-45.3) tumours, multiple myeloma (IR=22.6, 95% CI=15.4-33.2) and among patients with advanced-stage cancers (IR=27.7, 95% CI=24.0-32.0) or those who received chemotherapy or no/symptomatic treatment. The adjusted RR (aRR) for VTE was highest among patients with pancreas (aRR=16.3, 95% CI=8.1-32.6) or brain cancer (aRR=19.8 95% CI=7.1-55.2), multiple myeloma (aRR=46.1, 95% CI=13.1-162.0) and among patients receiving chemotherapy, either alone (aRR=18.5, 95% CI=11.9-28.7) or in combination treatments (aRR=16.2, 95% CI=12.0-21.7).
Although titanium dioxide (TiO2) is generally regarded as a nontoxic mild pulmonary irritant, some laboratory studies have reported lung adenomas in rats exposed to high levels of TiO2. Limited data on health effects among humans exist. A retrospective cohort mortality studywas conducted among 4241 TiO2 workers who were employed for at least 6 months, on or after January 1, 1960, at four TiO2 plants in the United States. Exposure categories, defined by plant, job title, and calendar years in the job, were created to examine mortality patterns in those jobs where the potential for TiO2 exposure is greatest. Standardized mortality ratios (SMRs) and their 95% confidence intervals (CI) were calculated to compare the mortality pattern of the workers with the general background population. Relative risks were estimated and trend tests were conducted to examine risk of disease among different exposure level groups in internal analyses. Workers experienced a significantly low overall mortality (SMR = 0.8; 95% CI = 0.8-0.9). No significantly increased SMRs were found for any specific cause of death. Deaths from lung cancer were as expected, and SMRs for this cancer did not increase with increasing TiO2 levels. Workers in jobs with greatest TiO2 exposure had significantly fewer than expected total deaths (SMR = 0.7; 95% CI = 0.6-0.9). Internal analyses […]
We performed nerve conduction studies (NCSs) on 113 chemical workers, many of whom had occupational exposure to the organophosphorus insecticide chlorpyrifos (O,O-diethyl-O-[3,5,6-trichloro-2-pyridyl]-phosphorothioate), to identify dose effects of subclinical neuropathy. In this masked longitudinal study, we estimated historic and interim chlorpyrifos exposures and measured excretion of 3,5,6 trichloro-2-pyridinol (TCP), a chlorpyrifos metabolite. TCP excretion among exposed workers suggested an estimated daily chlorpyrifos exposure averaging about 576-627 microg/day and indicated levels approximately 30% (range 0-250%) of the internal dose received by a typical subject exposed during a working day at the threshold limit value of 200 microg/m3. We modeled NCS results using linear mixed models with repeated measures. Although we found no consistent associations between interim chlorpyrifos exposure and NCS results, we identified several significant associations involving historic chlorpyrifos exposure. Most associations, however, reflected effects at low-exposure levels (< 20 mg/m3 x days) without further effects as exposure increased over a 10-fold range (20-220 mg/m3 x days). This suggested small differences among subjects with low or no chlorpyrifos exposure, rather than a dose-related deterioration among subjects with higher exposures. Two NCS results demonstrating apparent subclinical adverse dose effects showed significant but unexplained interaction with education level. The overall results provide little support […]