To prospectively evaluate the effectiveness, safety, and clinical benefits of once-weekly epoetin alfa therapy as an adjunct to chemotherapy in anemic cancer patients.
A total of 3,012 patients with ...nonmyeloid malignancies who received chemotherapy were enrolled onto this multicenter, open-label, nonrandomized study conducted in 600 United States community-based practices. Patients received epoetin alfa 40,000 U once weekly, which could be increased to 60,000 U once weekly after 4 weeks dependent on hemoglobin response. Treatment was continued for a maximum of 16 weeks.
Among the 2,964 patients assessable for efficacy, epoetin alfa therapy resulted in significant increases in hemoglobin levels, decreases in transfusion requirements, and improvements in functional status and fatigue as assessed by the linear analog scale assessment (energy level, ability to perform daily activities, and overall quality of life) and the anemia subscale of the Functional Assessment of Cancer Therapy-Anemia questionnaire. Improvements in quality-of-life parameters correlated significantly (P <.001) with increased hemoglobin levels. The direct relationship between hemoglobin and quality-of-life improvement was sustained during the 16-week study period, which is similar to findings of large community-based trials of three-times-weekly dosing. Once-weekly epoetin alfa was well tolerated, with most adverse events attributed to the underlying disease or concomitant chemotherapy.
The results from this large, prospective, community-based trial suggest that once-weekly epoetin alfa therapy increases hemoglobin levels, decreases transfusion requirements, and improves quality of life in patients with cancer and anemia who undergo concomitant chemotherapy. Based on the results of this study, the clinical benefits and the adverse event profile of once-weekly epoetin alfa therapy in community-based practice are similar to those observed in the historical experience with the three-times-weekly dosage schedule.
Chemotherapy-related anemia is prevalent among patients with hematologic malignancies. A randomized, open-label, multicenter trial of early versus late epoetin alfa in this population was conducted, ...focusing on quality of life (QOL).
Patients with non-Hodgkin lymphoma, Hodgkin lymphoma, chronic lymphocytic leukemia, or multiple myeloma and baseline hemoglobin of 10 to 12 g/dL who were scheduled for > or = 4 months of myelosuppressive chemotherapy were randomized to receive < or = 16 weeks of epoetin alfa at a dose of 40,000 U once weekly immediately (early) or to wait and only receive epoetin alfa if hemoglobin decreased to < 9 g/dL (late). Those patients with a hemoglobin level > 12 g/dL after 3 chemotherapy cycles were not randomized. The primary endpoint was a mean change in the Functional Assessment of Cancer Therapy-Anemia (FACT-An) total.
In all, 269 patients with a hemoglobin level < or = 12 g/dL were randomized. The mean total FACT-An increased 3.84 (95% confidence interval 95% CI, 0.21-7.46) in early patients and decreased 4.37 (95% CI, -7.99 to -0.74) in late patients (P = .003). Early patients had significantly (P < .05) higher mean scores for total FACT-General; FACT-General physical and functional well-being subscales, total anemia scale, and fatigue subscale; and daily activity, energy, and important activity Linear Analog Scale Assessment scales, as well as reduced bedrest days and restricted activity days. The mean hemoglobin increased 1.2 g/dL (95% CI, 0.98-1.46) in early patients but decreased 0.2 g/dL (95% CI, -0.32-0.12) in late patients (P < .0001). Adverse events were similar between groups (with fatigue being the most prevalent); clinically relevant thromboembolic events were more common in early patients.
Treating mild anemia immediately with epoetin alfa during chemotherapy for hematologic malignancy significantly improved QOL, productivity, and hemoglobin compared with delaying treatment until the hemoglobin level decreases to < 9.0 g/dL.
A retrospective subset analysis of anemic lung cancer patients who participated in three large, multicenter, community-based studies of 3-times-weekly (TIW) or once-weekly (QW) recombinant human ...erythropoietin (r-HuEPO, epoetin alfa) as an adjunct to chemotherapy was conducted. Patients were treated with epoetin alfa 150 U/kg in the first TIW study and with 10,000 U subcutaneously in the other study, with doubling of the dose if hemoglobin (Hb) response was inadequate. Patients in the QW study received epoetin alfa 40,000 U subcutaneously, which could be increased to 60,000 U. The maximum treatment duration for all three studies was 16 weeks. A total of 1748 lung cancer patients were evaluable for hematopoietic response; 1298 were evaluable for analyses of energy and 1300 were evaluable for analyses of activity and overall quality of life (QOL), as measured by the linear analogue scale assessment (LASA). Within 2 months of therapy, TIW and QW epoetin alfa therapy resulted in significant increases in Hb levels, decreases in transfusion requirements, and improvements in self-reported LASA scores. Increased Hb levels and reduced transfusion rates were demonstrated in the individual studies and in the analysis of data pooled from all three studies. Improvements in QOL parameters were significantly correlated with increased Hb levels. Epoetin alfa was well tolerated in all studies. The clinical benefits and safety profiles of the TIW and the QW schedules appear to be similar. In addition, the QW schedule provides greater convenience to patients and physicians alike. Given the high incidence of anemia and transfusion utilization in patients presenting with lung cancer, epoetin alfa is an effective strategy for correcting anemia in these patients, thereby improving their energy levels, activity levels, and overall QOL.
A study was undertaken to ascertain the effects of recombinant human erythropoietin (r-HuEPO) on renal function in chronic renal failure predialysis patients. The effect of improvement of anemia by ...r-HuEPO on the rate of decline in renal function in predialysis patients has not been previously studied prospectively in a large number of patients using reliable measures of glomerular filtration rate (GFR). To investigate the efficacy, safety, and impact of r-HuEPO therapy in chronic renal insufficiency patients, a 48-week, randomized, open-label, multicenter study was initiated in 83 anemic, predialysis (serum creatinine 3 to 8 mgldL) patients. Serial GFRs were measured using 125I-iothalamate clearance. Forty patients were randomized to the untreated arm and 43 patients to the treatment arm (50 Ulkg r-HuEPO subcutaneously three times weekly). Baseline characteristics were comparable for the r-HuEPO-treated and untreated groups. During this 48-week study, GFR, mean arterial blood pressure, and daily protein intake were not significantly different between the two groups. There was a statistically significant increase in hematocrit for the r-HuEPO-treated group that was not associated with acceleration of deterioration in residual renal function. This was demonstrated by the lack of a significant (P = 0.376) between-group difference in mean change in GFR from baseline to last available value for the r-HuEPO-treated (-2.1 ± 3.2 mUmin) and untreated (-2.8 ± 3.5 mUmin) groups. This study concludes that r-HuEPO therapy improves anemia in predialysis patients and does not accelerate the rate of progression to end-stage renal disease.
ABSTRACT
Objectives: To evaluate the relationship between hemoglobin (Hb) level and quality of life (QOL) in anemic patients with non-dialysis chronic kidney disease receiving epoetin alfa.
Patients ...and methods: A post-hoc analysis using data from a multicenter, open-label, prospective study of epoetin alfa for anemia in patients with chronic kidney disease not on dialysis was conducted. The relationship between Hb and QOL was analyzed using correlation and longitudinal analyses, the latter adjusting for sample selection bias. The Linear Analog Scale Assessment (LASA) and the Kidney Disease Questionnaire (KDQ) subscales were used to measure QOL. The impact of an incremental 1 g/dL increase in Hb level on LASA and KDQ scores was determined using an incremental analysis.
Results: A total of 1183 and 1044 patients formed the study populations for the LASA and KDQ analyses, respectively. There was a positive and significant relationship between Hb levels and QOL ( p < 0.05). Using non-linear regression analysis, we characterized the sigmoid-shape of the relationship between Hb levels and QOL scores. Hemoglobin change was a statistically significant determinant of QOL improvement for both LASA and KDQ scales ( p < 0.05). The model predicted that, based on a 2 unit change in Hb, the greatest incremental QOL improvement per unit of Hb increase occurred when Hb was in the range of 11 to 12 g/dL.
Conclusions: This study demonstrates that, beyond the well-known relationship between Hb increases and QOL improvements, the maximal incremental gain in QOL occurred when Hb reached 11 to 12 g/dL. This suggests that treating anemic patients with non-dialysis chronic kidney disease until their Hb level reaches 12 g/dL will result in the greatest QOL improvement per Hb unit increase. The analyses were conducted based on an open-label study of epoetin alfa and could be further validated using a randomized, controlled trial, comparing incremental gains in QOL associated with treatment initiation at varying levels of Hb across arms.
REMS are a particularly important issue for oncology and the National Comprehensive Cancer Network (NCCN). A disproportionate number of drugs with complex REMS are used in patients with cancer or ...hematologic disorders. REMS policies and processes within oncology may act as a model for other clinical areas. A breadth of experience and access to a wide knowledge base exists within oncology that will ensure appropriate development and consideration of the practical implications of REMS. NCCN is uniquely positioned to assume a leadership role in this process given its status as the arbiter of high-quality cancer care based on its world-leading institutions and clinicians. Notwithstanding the potential benefits, the successful design, implementation, and analysis of the FDA's recent requirement for REMS for some high-risk drugs and biologics will present significant challenges for stakeholders, including patients, providers, cancer centers, manufacturers, payors, health information technology vendors, and regulatory agencies. To provide guidance to these stakeholders regarding REMS challenges, the NCCN assembled a work group comprised of thought leaders from NCCN Member Institutions and other outside experts. The Work Group identified challenges across the REMS spectrum, including the areas of standardization, development and assessment of REMS programs, medication guides, provider knowledge and impact on prescribing, provider burden and compensation, and incorporation of REMS into clinical practice.
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).
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.
Some 3,634 geriatric patients were compared with 3,467 younger patients. From baseline to final measurement, EPO therapy significantly increased Hb by 2.0 g/dl in patients > or =65 years and 1.9 g/dl in patients <65 years (P<0.0001) and reduced transfusion utilization in both groups (P<0.006). Both age groups also had significant improvements in quality of life (QOL), measured by the 100-mm Linear Analog Assessment Scale (LASA). In younger patients, mean LASA changes were significantly greater than those in geriatric patients (P<0.05); however, QOL improvements in both age groups were clinically meaningful. There were no significant differences across geriatric age subgroups or between TIW and QW regimens for Hb change or QOL improvement. Overall hematopoietic response rate to EPO was 65.4% for patients > or =65 years and 64.7% for patients <65 years. Predictors of greater hematopoietic response (based on a pooled analysis) included lower body weight, baseline Hb, and baseline serum erythropoietin levels; better tumor response; and history of EPO dose reduction and longer time on study.
Anemic geriatric patients receiving EPO for CRA responded comparably to younger patients <65 years and should be treated similarly.
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