Huei-Ting Tsai

Effectiveness of Primary Androgen-Deprivation Therapy for Clinically Localized Prostate Cancer

PURPOSE Primary androgen-deprivation therapy (PADT) is often used to treat clinically localized prostate cancer, but its effects on cause-specific and overall mortality have not been established. Given the widespread use of PADT and the potential risks of serious adverse effects, accurate mortality data are needed to inform treatment decisions. METHODS We conducted a retrospective cohort study using comprehensive utilization and cancer registry data from three integrated health plans. All men were newly diagnosed with clinically localized prostate cancer. Men who were diagnosed between 1995 and 2008, were not treated with curative intent therapy, and received follow-up through December 2010 were included in the study (n = 15,170). We examined all-cause and prostate cancer-specific mortality as our main outcomes. We used Cox proportional hazards models with and without propensity score analysis. RESULTS Overall, PADT was associated with neither a risk of all-cause mortality (hazard ratio [HR], 1.04; 95% CI, 0.97 to 1.11) nor prostate-cancer-specific mortality (HR, 1.03; 95% CI, 0.89 to 1.19) after adjusting for all sociodemographic and clinical characteristics. PADT was associated with decreased risk of all-cause mortality but not prostate-cancer-specific mortality. PADT was associated with decreased risk of all-cause mortality only among the subgroup of men with a high risk of cancer progression (HR, 0.88; 95% CI, 0.78 to 0.97). CONCLUSION We found no mortality benefit from PADT compared with no PADT for most men with clinically localized prostate cancer who did not receive curative intent therapy. Men with higher-risk disease may derive a small clinical benefit from PADT. Our study provides the best available contemporary evidence on the lack of survival benefit from PADT for most men with clinically localized prostate cancer.

Efficacy of intermittent androgen deprivation therapy vs conventional continuous androgen deprivation therapy for advanced prostate cancer: a meta-analysis.

OBJECTIVE To compare the efficacy of intermittent androgen deprivation therapy (IADT) vs continuous androgen deprivation therapy (CADT) for the treatment of advanced prostate cancer; we performed a meta-analysis of randomized controlled trials (RCTs), assessing the risks of disease progression, all-cause, and disease-specific mortality. MATERIALS AND METHODS We conducted a systematic search of several bibliographic systems to identify all RCTs of IADT in men with newly diagnosed metastatic or biochemical only prostate cancer. We abstracted outcome data, study characteristics, and participant demographics. We performed heterogeneity tests and calculated the summarized risk differences (RD) and risk ratios at 95% confidence intervals (CI), using inverse variance methods in random-effects approaches. RESULTS We identified 8 RCTs (N = 4664) comparing mortality between IADT and CADT. For all men combined, we observed small but nonsignificant differences in all-cause mortality (RD = 0.02, 95% CI = -0.02, 0.06), disease-specific mortality (RD = 0.04, 95% CI = -0.01, 0.08), and disease progression (RD = -0.03, 95% CI = -0.09, 0.04). Among the prespecified subgroup with histologically confirmed, newly diagnosed metastatic disease, we found no difference in overall survival (RD = 0.00, 95% CI = -0.09, 0.09). CONCLUSION We found no difference in overall survival, but a small increased risk in disease-specific survival for men treated with IADT relative to CADT was observed. IADT could be considered as an alternative to CADT because of better quality of life outcome. Patients should be informed of the possible risks and benefits of both therapies. More research confirming the benefits of IADT vs CADT is needed to inform treatment decisions.

Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study

BACKGROUND Cardiovascular risk attributable to bevacizumab (Avastin(®), BEV) for treatment of metastatic colorectal cancer (CRC) remains unclear. We conducted a population-based cohort study to assess the safety of BEV use among patients aged ≥ 65. PATIENTS AND METHODS We identified CRC patients diagnosed from 2005 to 2007 who received chemotherapy and were followed until 31 December 2009. Outcomes were 3-year risk of arterial thromboembolic events (ATEs), cardiomyopathy or congestive heart failure (CM/CHF), and cardiac death (CD) after chemotherapy initiation. We fitted Cox-proportional hazards (PHs) models with inverse-probability-of-treatment-weights and calculated hazard ratios (HRs) for the risk of adverse events. RESULTS We identified 6803 CRC patients (median age: 73 years). Those with cardiac comorbidity were less likely to receive BEV (P < 0.0001). BEV is associated with an elevated risk of ATEs (HR = 1.82, 95% CI = 1.20-2.76, P < 0.001; rate difference: 3.5 additional cases/1000 person-years). We observed no association between BEV and CD or CM/CHF. CONCLUSIONS In general practice, the cardiovascular risk of BEV in elderly CRC is modest. The observed ATEs risk is lower than reported in clinical trials, which may be due to careful patient selection. Our findings may facilitate clinical decision-making of BEV use in elderly patients.

Risk of diabetes among patients receiving primary androgen deprivation therapy for clinically localized prostate cancer

PURPOSE Androgen deprivation therapy may increase diabetes risk. As the benefits of primary androgen deprivation therapy for localized prostate cancer are controversial, and most prostate cancer survivors are of advanced age with comorbidities, it is important to determine if primary androgen deprivation therapy increases the risk of diabetes and to determine the susceptibility factors. MATERIALS AND METHODS We conducted a retrospective cohort study of 12,191 men diagnosed with incident localized prostate cancer during 1995 to 2008, age 35 to 100 years, and without diabetes or receipt of prostatectomy or radiation 1 year after diagnosis. Patients were enrolled in 1 of 3 managed health plans and followed through 2010. Primary androgen deprivation therapy was defined as androgen deprivation therapy within 1 year after diagnosis. Incident diabetes was ascertained using inpatient and outpatient diagnosis codes, diabetes medications and hemoglobin A1c values. We estimated primary androgen deprivation therapy associated diabetes risk using Cox proportional hazard models in conventional and propensity score analyses. RESULTS Diabetes developed in 1,203 (9.9%) patients during followup (median 4.8 years) with incidence rates of 2.5 and 1.6 events per 100 person-years in the primary androgen deprivation therapy and nonprimary androgen deprivation therapy groups, respectively. Primary androgen deprivation therapy was associated with a 1.61-fold increased diabetes risk (95% CI 1.38-1.88). The number needed to harm was 29. The association was stronger in men age 70 or younger than in older men (HR 2.25 vs 1.40, p value for interaction=0.008). CONCLUSIONS Primary androgen deprivation therapy may increase diabetes risk by 60% and should be used with caution when managing localized prostate cancer. Because of the consistent association between androgen deprivation therapy and greater diabetes risk across disease states, we recommend routine screening and lifestyle interventions to reduce the risk of diabetes in men receiving androgen deprivation therapy.

Population-based study of the effect of gene expression profiling on adjuvant chemotherapy use in breast cancer patients under the age of 65 years.

Gene expression profiling (GEP) testing can help to predict the risk of cancer recurrence and guide decisions about adjuvant chemotherapy for breast cancer (BC). However, no prior US studies have evaluated the relation between GEP testing and the use of adjuvant chemotherapy by women treated in a general oncology practice.

Cardiovascular toxicity after antiangiogenic therapy in persons older than 65 years with advanced renal cell carcinoma

Sorafenib and sunitinib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) approved in 2005 and 2006, respectively, for the treatment of patients with renal cell carcinoma (RCC). A population‐based, observational cohort study of the cardiovascular risk of VEGFR TKI therapy in elderly RCC patients was conducted.

Utilization of bevacizumab in US elderly patients with colorectal cancer receiving chemotherapy

Objective Bevacizumab, the first FDA-approved anti-angiogenesis agent, has been used for metastatic colorectal cancer since 2004. This study evaluated the utilization of bevacizumab among elderly metastatic colorectal cancer patients in the United States. Methods Using Surveillance and Epidemiology and End Results (SEER)-Medicare data, this retrospective cohort study consisted of individuals aged 65 years or older with a colorectal cancer diagnosis between 2005 and 2009, who received chemotherapy any time through 2010. This included patients with newly diagnosed metastatic colorectal cancer and patients who progressed from initially diagnosed earlier-stage disease. We ascertained comorbid conditions using ICD-9 codes and conducted logistic regression to identify patients’ characteristics associated with bevacizumab use. Results A total of 8645 patients were identified (mean age 74 years; 52% male); 57% of patients received bevacizumab with initially diagnosed metastatic colorectal cancer and 44% of patients with treated progressive or recurrent disease. After adjusting for other covariates, we found that patients aged ≥80 years were less likely to receive bevacizumab compared with those aged 65–69 years (odds ratio (OR), 0.64 (95% confidence interval (CI): 0.57–0.73)), or if they had evidence of comorbid cardiomyopathy/congestive heart failure (OR, 0.82 (CI: 0.70–0.95)) or arrhythmic disorder (OR, 0.85 (CI: 0.75–0.96)). Adoption of bevacizumab into practice was rapid following its approval, and the use increased from 36% to 40% from 2005 to 2010 (p = 0.013). There were significant regional variations in bevacizumab use. Conclusions Despite rapid uptake since its original approval, there appears to be low use of bevacizumab in elderly metastatic colorectal cancer patients in the United States. Regional variations and the strong effects of age and comorbidity suggest lack of consensus among oncologists regarding benefits and risks of bevacizumab in elderly patients.

The effects of cardiovascular disease on the clinical outcome of elderly patients with diffuse large B-cell lymphoma

Abstract We identified 3910 elderly (>65 yrs) patients with diffuse large B-cell lymphoma (DLBCL) who received doxorubicin-based (+/−rituximab) therapy and 77 347 cancer-free controls, and assessed cardiovascular events and survival in relation to preexisting cardiovascular comorbidities. Compared to controls, patients with DLBCL had a 3.4-fold (95%CI 3.0–3.9) and 2.5-fold (95%CI 2.3–2.7) increased risk of congestive heart failure (CHF)/cardiomyopathy (CM) within 6 months and 3 years of diagnosis, respectively. Risk of acute myocardial infarction (AMI) was similarly increased. The risk of CHF/CM and AMI was significantly higher in those patients with DLBCL (vs. controls) who did not report preexisting cardiovascular disease, compared to those who had preexisting cardiovascular disease; this was due to dose reductions of doxorubicin among patients with preexisting cardiovascular disease. Rituximab improved survival in patients with stage III–IV (but not I–II) disease (p-interaction = 0.0003). Our novel findings emphasize the need to reduce cardiac toxicity of doxorubicin in elderly DLBCL patients.

Risks of Serious Toxicities from Intermittent versus Continuous Androgen Deprivation Therapy for Advanced Prostate Cancer: A Population Based Study

Purpose: Randomized trials have shown that intermittent androgen deprivation therapy for patients with advanced prostate cancer may improve sexual and physical functioning compared to continuous androgen deprivation therapy without compromising survival. To our knowledge it is unknown whether intermittent androgen deprivation therapy alters the risk of serious toxicities associated with continuous androgen deprivation therapy. Materials and Methods: We performed a population based cohort study of 9,772 men 66 years old or older who were diagnosed with advanced prostate cancer from 2002 to 2011 and treated with androgen deprivation therapy. Intermittent androgen deprivation therapy was defined as a single 90‐day interval between 2 androgen deprivation therapy sessions during which patients visited their physicians or underwent prostate specific antigen testing. Outcomes included acute myocardial infarction, stroke, heart failure, type 2 diabetes and fracture. We used Cox proportional hazard models to estimate the HRs of the comparative risk of serious toxicities between intermittent and continuous androgen deprivation therapy. Results: A total of 2,113 (22%), 769 (9%) and 899 men (9%) had a new cardiovascular event, diabetes or fracture, respectively, within 5 years of starting androgen deprivation therapy. Compared to the continuous androgen deprivation therapy group, the intermittent therapy group was at lower risk for serious cardiovascular events (HR 0.64, 95% CI 0.53–0.77), particularly in reducing the risk of heart failure (HR 0.62, 95% CI 0.49–0.78) and fracture (HR 0.52, 95% CI 0.38–0.70, each p <0.0001). Conclusions: Intermittent androgen deprivation therapy was associated with a lower risk of heart failure and fracture compared to continuous androgen deprivation therapy. This raises toxicity concerns for continuous relative to intermittent therapy and suggests that intermittent androgen deprivation therapy may represent a safer therapeutic choice in elderly men with advanced prostate cancer.

Adoption of Intermittent Androgen Deprivation Therapy for Advanced Prostate Cancer: A Population Based Study in American Urology Practice

Introduction: In several developed countries intermittent androgen deprivation therapy has been accepted over continuous androgen deprivation therapy for advanced prostate cancer management. To our knowledge its adoption and predictors of use in American urology practice remain unknown. Methods: Using SEER‐Medicare data we identified a cohort of men 66 years old or older who were newly diagnosed with prostate cancer with metastasis or with treated recurrence in whom androgen deprivation therapy was started during 2003 to 2007. We determined intermittent androgen deprivation therapy receipt based on interruptions longer than 3 months between scheduled and actual therapy injections, and physician visits and prostate specific antigen tests during the interruption. Predictors included patient and physician characteristics. We performed logistic regression analysis separately in the metastatic and treated recurrence groups using generalized estimating equations to account for the clustering effect of patients treated by the same physician. Results: Our cohort included 4,281 men, of whom 2,487 with metastasis and 1,794 with treated recurrence received intermittent androgen deprivation therapy. In patients who received intermittent rather than continuous therapy the median duration of therapy was by 6.4 and 9.0 months longer in those with metastasis and treated recurrence, respectively. Each patient group showed significant variation in intermittent therapy use by region (p <0.0001). There was lower intermittent androgen deprivation therapy use in the Eastern and Central regions than in the Mountain and Pacific regions. Conclusions: Intermittent androgen deprivation therapy has not been widely used in American urology practice. Its adoption shows substantial variation by geographic regions. These regional differences likely reflect uncertainty regarding the efficacy of this therapy among providers as well as differences in patient preferences and involvement in treatment decision making.