Real-World Use of Fostamatinib in Patients with Immune Thrombocytopenia and Thrombotic Risk.

Patients with immune thrombocytopenia (ITP) are at increased risk for bleeding and are paradoxically at increased risk for thrombosis. Many patients with ITP have underlying cardiovascular (CV) disease and/or other thrombotic risk factors for which considerable attention to selecting a therapeutic agent to manage ITP is needed. Fostamatinib, a spleen tyrosine kinase inhibitor, may reduce the risk of thrombosis while not interfering with hemostasis. We present a case series of 5 patients with ITP who had significant CV histories; each had at least 2 thrombotic risk factors. After unsuccessful management of ITP with other treatments, fostamatinib was initiated, was observed to be tolerable, and provided a durable platelet response without associated thromboembolic events. Fostamatinib may be the treatment of choice for patients with ITP in whom use of prothrombotic treatments should be avoided and/or continued use of antiplatelet or anticoagulant medication is needed.

Fostamatinib disodium hexahydrate: a novel treatment for adult immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease associated with substantial heterogeneity and varying outcomes. Significant bleeding, including intracranial hemorrhage, is a persistent risk for patients with ITP, along with cardiovascular disease. ITP has also been associated with decreased patient functionality and quality of life. The primary goal of ITP therapy is to lower the risk of bleeding and associated complications by raising platelet counts to levels that provide adequate hemostasis with minimal treatment-related toxicity. Current first-line treatments include corticosteroids, as well as intravenous and anti-D immunoglobulin. Despite the availability of several second-line options, the need for additional treatment options that can provide a stable, long-term response with few adverse effects is critical and ongoing. Fostamatinib disodium hexahydrate is an oral spleen tyrosine kinase inhibitor that produces a rapid, durable response in patients who have failed one or other treatments. Additionally, fostamatinib is well tolerated, and adverse effects can be actively mitigated through dose reduction, dose interruption, or standard therapeutic approaches.

Tasquinimod in the treatment of castrate-resistant prostate cancer - current status and future prospects.

Treatment options have significantly expanded in recent years for men with metastatic castration-resistant prostate cancer (mCRPC), with the routine use of immunotherapy (sipuleucel-T) and novel hormonal agents such as enzalutamide and abiraterone acetate prior to taxane-based chemotherapy or radium-223 radiotherapy. A number of immune checkpoints limit the immune response of the host to metastatic tumor progression in prostate cancer, one of which is an immunosuppressive and pro-angiogenic cell called the myeloid-derived suppressor cell (MDSC). Tasquinimod is a small molecular oral inhibitor of S100A9, a key cell surface regulator of MDSC function, and has shown anti-angiogenic, antitumor and immune-modulatory properties in preclinical models of prostate cancer and other solid tumors. A large randomized phase II trial of tasquinimod in men with chemotherapy-naïve mCRPC demonstrated a significant prolongation in radiographic and symptomatic progression-free survival compared with placebo, which was also associated with improvements in overall survival. Tasquinimod was studied in a global phase III randomized trial in men with bone mCRPC and, while it significantly improved radiographic progression-free survival, this did not result in an overall survival benefit. However, tasquinimod is under evaluation as well as a combination therapy with other systemic agents in prostate cancer and as a single agent in other solid tumors. This review encompasses the preclinical and clinical development of tasquinimod as a therapy for men with prostate cancer.

Patterns and correlates of prostate cancer treatment in older men.

BACKGROUND: Although elderly men, particularly patients with low-risk prostate cancer and a life expectancy less than 10 years, are unlikely to benefit from prostate cancer active therapy, treatment rates in this group are high. METHODS: By using the population-based Surveillance, Epidemiology, and End Results program linked to Medicare data from 2004 to 2005, we examined the effects of clinical and nonclinical factors on the selection of prostate cancer active therapy (ie, radical prostatectomy, external beam radiation therapy, brachytherapy, or androgen deprivation therapy) in men aged≥75 years with a new diagnosis of localized prostate cancer. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for receiving prostate cancer active therapy. RESULTS: The majority of men aged≥75 years were treated with prostate cancer active therapy (81.7%), which varied by disease risk level: low, 72.2%; intermediate, 83.7%; and high, 86.4%. Overall, in older men, the percentage of the total variance in the use of prostate cancer active therapy attributable to clinical and nonclinical factors was minimal, 5.1% and 2.6%, respectively. In men with low-risk disease, comorbidity status did not affect treatment selection, such that patients with 1 or 2+ comorbidities were as likely to receive prostate cancer active therapy as healthy men: OR=0.98; 95% CI, 0.76-1.27 and OR=1.19; 95% CI, 0.84-1.68, respectively. Geographic location was the most powerful predictor of treatment selection (Northeast vs Greater California: OR=2.41; 95% CI, 1.75-3.32). CONCLUSION: Clinical factors play a limited role in treatment selection among elderly patients with localized prostate cancer.

Risk profiles and treatment patterns among men diagnosed as having prostate cancer and a prostate-specific antigen level below 4.0 ng/ml.

BACKGROUND: Despite controversy over the benefit of prostate-specific antigen (PSA) screening, little is known about risk profiles and treatment patterns in men diagnosed as having prostate cancer who have a PSA value less than or equal to 4.0 ng/mL. METHODS: We used data from the Surveillance, Epidemiology, and End Results system to describe patient characteristics and treatment patterns in the cases of 123 934 men with newly diagnosed prostate cancer from 2004 to 2006. Age-standardized treatment rates were calculated in 5-year age strata. Logistic regression was used to quantify the odds ratios (ORs) of men with low- and high-risk disease and the use of radical prostatectomy (RP) or radiation therapy (RT). RESULTS: Men with a PSA level of 4.0 ng/mL or lower represent 14% of incident prostate cancer cases. Fifty-four percent of men diagnosed as having prostate cancer and PSA levels lower than 4.0 ng/mL harbor low-risk disease (stage, < or =T2a, PSA level, < or =10 ng/mL, and Gleason score, < or =6), but over 75% of them received RP or RT. Men with screen-detected prostate cancer and PSA values lower than 4 ng/mL were 1.49 (95% confidence interval [CI], 1.38-1.62) and 1.39 (95% CI, 1.30-1.49) times more likely to receive RP and RT, respectively, and were less likely to have high-grade disease than men who had non-screen-detected prostate cancer (OR, 0.67; 95% CI, 0.60-0.76). CONCLUSIONS: Most men diagnosed as having prostate cancer with a PSA threshold below 4.0 ng/mL had low-risk disease but underwent aggressive local therapy. Lowering the biopsy threshold but retaining our inability to distinguish indolent from aggressive cancers might increase the risk of overdiagnosis and overtreatment.

Contemporary risk profile of prostate cancer in the United States.

National-level data that characterize contemporary prostate cancer patients are limited. We used 2004-2005 data from the Surveillance, Epidemiology, and End Results Program to generate a contemporary profile of prostate cancer patients (N = 82 541) and compared patient characteristics of this 2004-2005 population with those of patients diagnosed in 1998-1989 and 1996-1997. Among newly diagnosed patients in 2004-2005, the majority (94%) had localized (ie, stage T1 or T2) prostate cancer and a median serum prostate-specific antigen (PSA) level of 6.7 ng/mL. Between 1988-1989 and 2004-2005, the average age at prostate cancer diagnosis decreased from 72.2 to 67.2 years, and the incidence rate of T3 or T4 cancer decreased from 52.7 per 100 000 to 7.9 per 100 000 among whites and from 90.9 per 100 000 to 13.3 per 100 000 among blacks. In 2004-2005, compared with whites, blacks were more likely to be diagnosed at a younger age (mean age: 64.7 vs 67.5 years, difference = 2.7 years, 95% confidence interval [CI] = 2.5 to 2.9 years, P < .001) and to have a higher PSA level at diagnosis (median PSA level: 7.4 vs 6.6 ng/mL, difference = 0.8 ng/mL, 95% CI = 0.6 to 1.0 ng/mL, P < .001). In conclusion, more men were diagnosed with prostate cancer at a younger age and earlier stage in 2004-2005 than in earlier years. The racial disparity in cancer stage at diagnosis has decreased statistically significantly over time.