Ionic exchange between electrostatically stabilized PMMA latex and aqueous dispersion of nanoparticles or rigid-rod polyelectrolytes of opposite sense is demonstrated to be a flexible approach to ...fabrication of polymeric-based nano and molecular composites, including layered silicates, indium tin oxide nanoparticles, rigid-rod polyelectrolyte, and carbon nanofibers. The exchange reaction produces a nanoscale coating on the polymer latex surface, providing efficient dispersion of the nanoparticle, interfacial control between the constituents, as well as the potential for hierarchical morphology control. The resulting nano and molecular scale dispersions are thermodynamically stable when an emulsifier that participates with the free-radical polymerization of the MMA is used. The result is direct ionic coupling between the polymer and the nanoparticle, but at a sufficiently low level to maintain solution and melt processibility. Molecular composites of sPBI and PMMA are discussed in detail, and demonstrate increases in heat distortion temperature (17 °C) and rubbery modulus (210%) with less than 1% incorporation of the rigid-rod polymer electrolyte.
This phase 3, randomized, double‐blind, placebo‐controlled study was designed to evaluate the efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies. ...Patients (n = 344) with lymphoma or myeloma received darbepoetin alfa 2·25 μg/kg or placebo s.c., once weekly for 12 weeks. The percentage of patients achieving a haemoglobin response was significantly higher in the darbepoetin alfa group (60%) than in the placebo group (18%) (P < 0·001), regardless of baseline endogenous erythropoietin level. However, increased responsiveness was observed in patients with lower baseline erythropoietin levels. Darbepoetin alfa also resulted in higher mean changes in haemoglobin than placebo from baseline to the last value during the treatment phase (1·80 g/dl vs 0·19 g/dl) and after 12 weeks of treatment (2·66 g/dl vs 0·69 g/dl). A significantly lower percentage of patients in the darbepoetin alfa group received red blood cell transfusions than in the placebo group (P < 0·001). The efficacy of darbepoetin alfa was consistent for patients with lymphoma or myeloma. Improvements in quality of life were also observed with darbepoetin alfa. The overall safety profile of darbepoetin alfa was consistent with that expected for this patient population. Darbepoetin alfa significantly increased haemoglobin and reduced red blood cell transfusions in patients with lymphoproliferative malignancies receiving chemotherapy.
Darbepoetin alfa is a novel erythropoiesis‐stimulating protein with a prolonged serum half‐life. This randomized, double‐blind, placebo‐controlled, dose‐finding study investigated the efficacy and ...safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies who were receiving chemotherapy. Patients were randomized in a 1:2:2:1 ratio to receive darbepoetin alfa 1·0 μg/kg (n = 11), 2·25 μg/kg (n = 22), 4·5 μg/kg (n = 22) or placebo (n = 11), administered subcutaneously once weekly for 12 weeks. No dose increases were allowed during the study. A higher proportion of patients achieved a haemoglobin response (defined as a ≥ 2·0 g/dl increase from baseline) in the darbepoetin alfa 1·0 μg/kg (45%), 2·25 μg/kg (55%) and 4·5 μg/kg (62%) groups than in the placebo group (10%; P < 0·01). The mean change in haemoglobin from baseline to week 13 was 1·56 g/dl in the 1·0 μg/kg group, 1·64 g/dl in the 2·25 μg/kg group and 2·46 g/dl in the 4·5 μg/kg group, compared with a mean change of 1·00 g/dl in the placebo group. The overall safety profile of darbepoetin alfa in this study was similar to that of placebo. These results show that darbepoetin alfa effectively and safely increased haemoglobin concentrations in patients with lymphoproliferative malignancies. Confirmative studies at doses of 2·25 and/or 4·5 μg/kg/week in this population are warranted.
Aims: To investigate the relationship between the framing of survival gains and the perceived value of cancer care. Methods: Through a population-based survey of 2040 US adults, respondents were ...randomized to one of the two sets of hypothetical scenarios, each of which described the survival benefit for a new treatment as either an increase in median survival time (median survival), or an increase in the probability of survival for a given length of time (landmark survival). Each respondent was presented with two randomly selected scenarios with different prognosis and survival improvements, and asked about their willingness to pay (WTP) for the new treatments. Results: Predicted WTP increased with survival benefits and respondents' income, regardless of how survival benefits were described. Framing therapeutic benefits as improvements in landmark rather than median time survival increased the proportion of the population willing to pay for that gain by 11-35%, and the mean WTP amount by 42-72% in the scenarios we compared. Conclusion: How survival benefits are described may influence the value people place on cancer care.
Current practice guidelines for the management of chemotherapy-induced anemia (CIA) recommend initiating erythropoietic intervention at hemoglobin (Hb) ≤ 10 g/dL (American Society of Hematology ...ASH/American Society of Clinical Oncology ASCO), or at Hb ≤ 11 g/dL (National Comprehensive Cancer Network NCCN). This comprehensive literature review summarizes published findings of randomized controlled trials (RCTs) that evaluated the effects of initiating erythropoietic treatment at Hb > 10 g/dL on transfusion incidence, Hb concentration, and/or patient-reported outcomes, relative to control. A search of the Medline database and conference proceedings (ASH and ASCO) from 1999 to 15 June 2004 was conducted to identify RCTs that evaluated the ability of erythropoietic agents to prevent the onset or worsening of CIA. Mantel-Haenszel weighted summary estimates of the relative risk were calculated to evaluate outcomes in patients treated with epoetin alfa compared to control patients. Using predefined selection criteria, 4 full-length papers (summarized in the table) and 5 abstracts (Chang ASCO 2003; Savonije ASCO 2004; Straus ASH 2003; Crawford ASCO 2003; Rearden ASCO 2004) were identified and reviewed. Epoetin alfa effectively decreased transfusion incidence and the percentage of patients with Hb decline to < 10 g/dL vs no treatment in 4 RCTs reported from 1997 onward (table). The estimated summary relative risk (95% CI) for transfusion and Hb < 10 g/dL are 0.39 (0.26–0.57; P < 0.0001) and 0.48 (0.25–0.89), respectively. These results were consistent with early results reported in 2 additional RCTs (Chang ASCO 2003; Savonije ASCO 2004), which were of similar design. The preliminary results of 3 additional RCTs that directly compared outcomes following early (Hb > 10 g/dL) and late (Hb ≤ 10 g/dL) erythropoietic intervention were presented at recent ASH and ASCO conferences (Straus ASH 2003; Crawford ASCO 2003; Rearden ASCO 2004). All 3 studies provided evidence of lower incidence of transfusion, higher Hb levels over time, and/or better patient-reported outcomes among patients treated early compared with those treated late. The results of the studies examined demonstrate the clinical benefits of initiating erythropoietic treatment at a Hb concentration > 10 g/dL, with respect to reducing transfusion requirements and improving Hb levels, in patients with cancer undergoing chemotherapy. Although the findings are preliminary and have yet to appear in peer-reviewed journals, the comparative RCTs of early vs late intervention point to a trend in which patients who received erythropoietic treatment early experienced better clinical outcomes overall than patients treated late.
Bamias 2003Thatcher 1999ten Bokkel Huinink 1998Del Mastro 1997Hb Eligibility Criterion (g/dL)≤13≥10.5< 13≥ 12Baseline Hb (g/dL)11.5 (E)13.7 (E)12.0 (E)13.0 (E)11.5 (C)13.4 (C)11.8 (C)13.1 (C)Transfusion Incidence (%)15* (E)45* (E)4**(E)0 (E)33 (C)59 (C)39 (C)6 (C)% Patients with Hb < 10 g/dLª17*** (E)48* (E)18* (E)0*** (E)46 (C)66 (C)50 (C)52 (C)Dosing Regimen10,000 U TIW150 U/kg TIW150 U/kg TIW150 U/kg TIWNo treatment (control)No treatment (control)No treatment (control)No treatment (control)E=epoetin alfa; C=no treatment control; reported p < 0.05 (*), 0.01 (**), 0.001 (***) vs control. ªHb ≤10 g/dL in Del Mastro study
The objective of this ongoing trial is to study the ability of darbepoetin alfa to reverse chemotherapy-induced anemia in cancer patients, and to relate improvement in hemoglobin with changes in ...fatigue and functional capacity. Eligible subjects had a nonmyeloid malignancy, were receiving multicycle chemotherapy, and were anemic, as defined by a screening hemoglobin < or = 11 g/dL. Darbepoetin alfa was administered at a starting dosage of 3 microg/kg every 2 weeks for up to eight doses (16 weeks) in an open-label, noncomparative setting. A total of 194 oncology practices contributed 1,173 subjects to this interim analysis. The mean increase in hemoglobin was 1.7 g/dL (95% CI: 1.6, 1.8) to last value on study (intent-to-treat analysis) and 2.1 g/dL (95% CI: 1.9, 2.2) for those patients receiving the full 16 weeks of therapy. The Kaplan-Meier estimate of the proportion of subjects with a hematopoietic response (increase in hemoglobin > or = 2 g/dL and/or hemoglobin value > or = 12 g/dL) was 84% (95% CI:81,86). Subjects in the lower baseline hemoglobin category (< 10 g/dL) tended to have a greater hemoglobin response during treatment. The Functional Assessment of Cancer Therapy-Fatigue (FACT-Fatigue) subscale score increased by a mean of 6.8 points (26%) during the study, and improvements in fatigue paralleled the increases observed in hemoglobin. Study treatment-related toxicity was minimal, with the most common event being injection-site pain, seen in 2% of subjects. Experience to date with an every-2-week regimen of darbepoetin alfa indicated efficacy comparable to historical experience with weekly and 3-times-weekly regimens of epoetin alfa in treating chemotherapy-induced anemia in cancer subjects.
Our objective was to evaluate the effects of darbepoetin alfa (Aranesp) on hemoglobin and transfusions in anemic patients with cancer undergoing chemotherapy, and the impact of age, sex, baseline ...hemoglobin, chemotherapy type, and tumor type. Patients were randomized to one of three darbepoetin alfa groups based on average weekly dose (< 1.5 microg/kg, 1.5 to 2.25 microg/kg, and > 2.25 microg/kg) or to placebo. Dose response was evaluated for change in hemoglobin, hemoglobin and hematopoietic responses, and red blood cell transfusion rates. Hazard ratios for the incidence of hemoglobin response and transfusions were calculated. Adverse events and antibody formation were assessed. Treatment effects were observedfor all hemoglobin end points and incidence of transfusion. The incidence of hematopoietic response among the darbepoetin alfa dose groups ranged from 46% (95% confidence interval CI = 33%-60%) to 74% (95% CI = 66%-81%) and increased with higher darbepoetin alfa dose. Patients receiving darbepoetin alfa were more likely to exhibit a hemoglobin response and less likely to require a transfusion, compared with placebo, irrespective of the patient characteristics examined. No increased risk of adverse events and no development of neutralizing antibodies were observed with darbepoetin alfa use. Darbepoetin alfa increased the likelihood of a hemoglobin response and decreased the need for transfusions in cancer patients with chemotherapy-induced anemia.
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