Rigosertib in combination with azacitidine in patients with myelodysplastic syndromes or acute myeloid leukemia: Results of a phase 1 study.

Phase 1 results from a Phase 1/2 study comprise 18 patients with myelodysplastic syndromes (MDS; n = 9), acute myeloid leukemia (AML; n = 8), and chronic myelomonocytic leukemia (CMML; n = 1) who were either hypomethylating agent naïve (n = 10) or relapsed/refractory following prior hypomethylating agent therapy (n = 8) (NCT01926587). Patients received oral rigosertib, an inhibitor of Ras-effector pathways, in 3 successive cohorts (140 mg twice daily, 280 mg twice daily, or 840 mg/day [560 mg morning/280 mg evening]) for 3 weeks of a 4-week cycle. Patients received parenteral azacitidine (75 mg/m/day × 7 days) during the second week; the cycle repeated every 4 weeks.

The GOLD ReGISTry: a Global, Prospective, Observational Registry Collecting Longitudinal Data on Patients with Advanced and Localised Gastrointestinal Stromal Tumours.

Background: Gastrointestinal stromal tumours (GISTs) are the most common gastrointestinal sarcomas. This global, prospective registry followed patients with advanced or localised GIST (2007-2011).

Methods: Current and evolving diagnostics, treatments and outcome measures in patients with GIST were assessed.

Nilotinib 300 mg BID as frontline treatment of CML: prospective analysis of the Xpert BCR-ABL monitor system and significance of 3-month molecular response.

Sixty patients with early chronic phase CML (ECPCML) received Nilotinib on a phase II study which included a comparison of the Xpert BCR-ABL Monitor™ PCR system with standardized (IS) BCR-ABL1 real-time quantitative PCR (RQ-PCR). 88% patients achieved MMR with 45% achieving MR4.5.

Rapid initial decline in BCR-ABL1 is associated with superior responses to second-line nilotinib in patients with chronic-phase chronic myeloid leukemia.

Background: We evaluated BCR-ABL1 kinetics in patients treated with nilotinib and analyzed whether a dynamic model of changes in BCR-ABL1 levels over time could be used to predict long-term responses.

Methods: Patients from the nilotinib registration trial (CAMN107A2101; registered at http://www.clinicaltrials.

Initial molecular response at 3 months may predict both response and event-free survival at 24 months in imatinib-resistant or -intolerant patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase treated with nilotinib.

Purpose: The association between initial molecular response and longer-term outcomes with nilotinib was examined.

Patients And Methods: Patients with imatinib-resistant or -intolerant chronic myeloid leukemia in chronic phase from the phase II nilotinib registration study with available postbaseline BCR-ABL1 transcript assessments were included (N = 237).

Results: BCR-ABL1 transcript levels (International Scale [IS]) at 3 months correlated with complete cytogenetic response (CCyR) by 24 months.

Nilotinib population pharmacokinetics and exposure-response analysis in patients with imatinib-resistant or -intolerant chronic myeloid leukemia.

Purpose: We evaluated the population pharmacokinetics (PK) and exposure-response relationship of nilotinib in patients with imatinib-resistant or -intolerant chronic myeloid leukemia (CML).

Methods: Concentration data from 493 patients with CML in chronic phase (CML-CP), accelerated phase, or blast crisis were used to perform a population pharmacokinetic analysis using nonlinear mixed-effect modeling. Steady-state nilotinib trough concentrations (Cmin) in individual patients were estimated from the population PK model for correlation with the efficacy and safety variables.

Minimal cross-intolerance with nilotinib in patients with chronic myeloid leukemia in chronic or accelerated phase who are intolerant to imatinib.

Nilotinib has significant efficacy in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) and in patients with CML-CP or CML in accelerated phase (CML-AP) after imatinib failure. We investigated the occurrence of cross-intolerance to nilotinib in imatinib-intolerant patients with CML. Only 1/75 (1%) patients with nonhematologic imatinib intolerance experienced a similar grade 3/4 adverse event (AE), and 3/75 (4%) experienced a similar persistent grade 2 nonhematologic AE on nilotinib.

Proinflammatory state, hepcidin, and anemia in older persons.

In patients with overt inflammatory diseases, up-regulated hepcidin impairs iron absorption and macrophage release, causing anemia. Whether the mild proinflammatory state of aging is associated with increased hepcidin is unknown. We characterized the relationships between urinary hepcidin, iron status, anemia, and inflammation in 582 patients 65 years or older participating in the InCHIANTI (Invecchiare in Chianti, "Aging in the Chianti Area") study, a population-based study of aging in Tuscany, Italy.

An extended dosing regimen of epoetin alfa 60,000 units every 2 weeks in anemic patients with cancer receiving chemotherapy.

Purpose: This open-label study evaluated the safety and efficacy of epoetin alfa 60,000 U once weekly Initialsly followed by 60,000 U every 2 weeks in anemic patients with cancer receiving chemotherapy.

Patients And Methods: Patients receiving weekly or every- 4-weeks chemotherapy regimens for nonmyeloid malignancy and with hemoglobin (Hb) level View Article and Find Full Text PDF

Anaemia and the risk of injurious falls in a community-dwelling elderly population.

Background: Anaemia in the elderly is associated with a number of health-related functional declines, such as frailty, disability and muscle weakness. These may contribute to falls which, in the elderly, result in serious injuries in perhaps 10% of cases.

Objective: To investigate whether anaemia increases the risk of injurious falls in an elderly population.

An extended maintenance dosing regimen of epoetin alfa 80,000 U every 3 weeks in anemic patients with cancer receiving chemotherapy.

Background: The purpose of this study was to evaluate the safety and efficacy of epoetin alfa (EPO) at an initial dose of 60,000 Units (U) once weekly (QW) followed by extended dosing of 80,000 U every 3 weeks (Q3W) in patients with chemotherapy-induced anemia (CIA).

Materials And Methods: Anemic patients (hemoglobin [Hb] < or = 11 g/dl) receiving Q3W chemotherapy for nonmyeloid malignancy were enrolled in this prospective, open-label, single-arm study to receive EPO 60,000 U subcutaneously (SC) QW (initial dosing phase [IDP]) until a target Hb level of 12 g/dl was reached (maximum 12 weeks). Patients who achieved an Hb level of 12 g/dl at any point during the IDP then entered the extended dosing phase (EDP; EPO 80,000 U SC Q3W).

Anemia and cancer in older persons.

Although the overall prevalence for many cancers is declining, cancer still remains a diagnosis more common in the elderly than in younger individuals. As the population ages, the proportion of patients with cancer who are elderly is expected to increase dramatically. Anemia occurs more often in older individuals for a variety of reasons, and its prevalence in elderly patients with cancer is significantly increasing.

Anemia, physical disability, and survival in older patients with heart failure.

Background: Anemia is common in congestive heart failure, and it has been associated with poor prognosis. The effect of anemia on functional ability in heart failure has not been described. We evaluated the relationship of anemia, physical disability, and survival in patients with heart failure.

Randomized, open-label comparison of epoetin alfa extended dosing (80 000 U Q2W) vs weekly dosing (40 000 U QW) in patients with chemotherapy-induced anemia.

Objective: This randomized, open-label, multicenter study compared the efficacy and safety of epoetin alfa (EPO) 80 000 U every 2 weeks (Q2W) to the FDA-approved regimen of 40 000 U weekly (QW) in patients with chemotherapy-induced anemia.

Research Design And Methods: A total of 310 patients with nonmyeloid malignancy and baseline hemoglobin (Hb) View Article and Find Full Text PDF

Anemia and cognitive performance in hospitalized older patients: results from the GIFA study.

Background: Anemia represents a major risk factor for adverse health-related events in older persons. The aim of this study was to evaluate the association between hemoglobin levels/anemia and cognitive function in hospitalized older persons.

Method: Data are from the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study.

Epoetin alfa increases hemoglobin levels and improves quality of life in anemic geriatric cancer patients receiving chemotherapy.

Goal: To evaluate epoetin alfa (EPO) treatment of anemia in geriatric cancer patients receiving chemotherapy, a retrospective subgroup analysis was conducted of anemic cancer patients > or =65 years of age from three 16-week community-based studies of thrice-weekly (TIW) or once-weekly (QW) EPO for chemotherapy-related anemia (CRA).

Patients And Methods: Analyses were conducted on the overall geriatric population (> or =65 years) and by age subgroup (65-74, 75-84, and > or =85 years), and compared with younger patients (<65 years) for each individual study and for pooled data.

Main Results: Some 3,634 geriatric patients were compared with 3,467 younger patients.

Anemia in old age is associated with increased mortality and hospitalization.

Background: Anemia is common in old age and has been shown to affect older persons' physical function. To more fully understand the detrimental health effects of anemia, we examined the relationship of anemia with death and hospitalization outcomes in a large community-based sample of older persons.

Methods: Data are from 3607 persons, aged 71 years or older, participating in the National Institute on Aging (NIA)-sponsored Established Populations for Epidemiologic Studies of the Elderly (EPESE) study.

Meaningful change and responsiveness in common physical performance measures in older adults.

Objectives: To estimate the magnitude of small meaningful and substantial individual change in physical performance measures and evaluate their responsiveness.

Design: Secondary data analyses using distribution- and anchor-based methods to determine meaningful change.

Setting: Secondary analysis of data from an observational study and clinical trials of community-dwelling older people and subacute stroke survivors.

Anemia and recovery from disability in activities of daily living in hospitalized older persons.

Objectives: To evaluate the predictive value of hemoglobin levels upon hospital admission on recovery from activity of daily living (ADL) disability during hospital stay in older patients.

Design: Longitudinal observational study.

Setting: Geriatric and internal medicine acute care units.

Anemia in the elderly: current understanding and emerging concepts.

Anemia is currently defined by the World Health Organization (WHO) as a hemoglobin (Hb) level <13 g/dL in men and <12 g/dL in women. While estimates vary widely, nearly one quarter of community-based octagenerians and one half of the chronically ill elderly have Hb levels that satisfy a diagnosis of anemia according to these criteria. A growing body of evidence has linked adverse events with even "mild" anemia or low-normal Hb in the elderly.

Proinflammatory state and circulating erythropoietin in persons with and without anemia.

Purpose: High circulating levels of proinflammatory cytokines cause anemia, perhaps by interacting with erythropoietin production or biological activity. We characterize the relationships of systemic inflammation, erythropoietin, and hemoglobin.

Methods: Data are from the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study population.

Renal function, erythropoietin, and anemia of older persons: the InCHIANTI study.

Background: In the older population, anemia has been associated with poor outcomes including disability and mortality. Understanding the mechanisms leading to anemia is essential to plan better treatment and prevention strategies. We tested the hypothesis that the age-related decline in kidney function is associated with an increased prevalence of anemia and that such an increase is accompanied by a concomitant decrement in erythropoietin levels.

Impact of anemia and cardiovascular disease on frailty status of community-dwelling older women: the Women's Health and Aging Studies I and II.

Background: The physiological basis of the geriatric syndrome of frailty, a clinical state of increased vulnerability to adverse outcomes such as disability and mortality, remains to be better characterized. We examined the cross-sectional relationship between hemoglobin (Hb) and a recently-validated measure of frailty in community-dwelling older women, and whether this relationship was modified by cardiovascular disease (CVD) status.

Methods: Data were pooled from women 70-80 years old participating in the Women's Health and Aging Studies I and II (Baltimore, MD, 1992-1996) with known frailty status and Hb > or = 10 g/dL (n = 670).

Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia.

Clinicians frequently identify anemia in their older patients, but national data on the prevalence and causes of anemia in this population in the United States have been unavailable. Data presented here are from the noninstitutionalized US population assessed in the third National Health and Nutrition Examination Survey (1988-1994). Anemia was defined by World Health Organization criteria; causes of anemia included iron, folate, and B(12) deficiencies, renal insufficiency, anemia of chronic inflammation (ACI), formerly termed anemia of chronic disease, and unexplained anemia (UA).