Once weekly versus twice weekly subcutaneous administration of recombinant human erythropoietin in haemodialysis patients. Once weekly versus twice weekly subcutaneous administration of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. rHuEPO in the treatment of postpartum anemia: subcutaneous versus intravenous administration. Efficacy of recombinant human erythropoietin administered subcutaneously to CAPD patients once weekly. Safety and efficacy of erythropoietin in children with chronic renal failure. Treatment of the anemia of chronic renal failure with subcutaneous recombinant human erythropoietin. The efficacy of once weekly compared with two or three times weekly subcutaneous epoetin beta: results from a randomized controlled multicentre trial. Swedish Study Group. Prevention of chemotherapy-induced anemia by the use of erythropoietin in patients with primary malignant bone tumors (a double-blind, randomized, phase III study). Effect of early versus late administration of human recombinant erythropoietin on transfusion requirements in premature infants: results of a randomized, placebo-controlled, multicenter trial.
Optimal route and frequency of administration of recombinant human erythropoietin (rHuEPO) have not yet been determined. There is some evidence to suggest that subcutaneous administration of rHuEPO may be more effective than the intravenous route in reversing renal anemia. It is also unclear whether rHuEPO is more effective when given by a large intermittent dose or by more frequent multiple divided doses. We have compared the effect of twice weekly versus once weekly subcutaneous administration of rHuEPO in two groups of haemodialysis patients. At the end of 12 weeks of treatment with rHuEPO, the mean haemoglobin levels had risen from 6.9 +/- (SD) 0.7 to 8.9 +/- 1.3 g/dl in the once weekly group and from 7.2 +/- 1.0 to 9.3 +/- 1.6 g/dl in the twice weekly group. The average doses of rHuEPO used during the study were 127 +/- 6 and 115 +/- 18 U/kg body weight/week for the once weekly and twice weekly groups, respectively. Subcutaneous administration of low-dose rHuEPO is effective in reversing renal anaemia. Similar responses were obtained with once weekly and twice weekly regimens. Twice weekly subcutaneous (s.c.) administration of recombinant human erythropoietin (rHuEPO) is effective in reversing renal anemia in CAPD patients. However the optimal frequency of administration has not been established. It would be more convenient to give rHuEPO by once weekly rather than twice weekly injection. We have therefore compared the effect of twice weekly versus once weekly s.c. administration of rHuEPO. Two groups of 10 CAPD patients were given the same starting dose of s.c. rHuEPO (100 U/kg body wt/week) either as a single weekly dose or twice weekly in divided doses. The rHuEPO dosage was then adjusted according to the hematologic response. The aim was to increase hemoglobin levels by about 1 g/dl per month. The target hemoglobin was 10 g/dl. After 16 weeks of treatment with rHuEPO, the hemoglobin levels rose from 6.6 +/- 1.2 (mean +/- SD) to 10.1 +/- 1.1 g/dl in the once weekly group and from 6.4 +/- 0.8 to 10.2 +/- 1.1 g/dl in the twice weekly group. The average doses of rHuEPO used during the study were 84 +/- 16 and 88 +/- 15 U/kg body wt/wk for the once weekly and twice weekly groups respectively. Subcutaneous administration of low dose rHuEPO is effective in reversing renal anemia. Similar responses were obtained with once weekly and twice weekly regimens. It is therefore acceptable and convenient for patients to receive one weekly s.c. injection of rHuEPO for the treatment of renal anemia. The aim of this study was to determine whether single-shot therapy with recombinant human erythropoietin (rHuEPO) is as effective as divided dosing in postpartum anemia for both subcutaneous and intravenous administration. In a randomized prospective study we treated 95 women with postpartum anemia (Hb < 10 g/dl) within 72 h after delivery with rHuEPO (total dose 300 U/kg body weight) and oral iron supplementation in four treatment groups: group A rHuEPO 150 U/kg s.c. once daily for two consecutive days; group B rHuEPO 150 U/kg i.v. once daily for two consecutive days; group C rHuEPO 300 U/kg s.c. once only; group D rHuEPO 300 U/kg i.v. once only. No significant intergroup differences were found in the mean increase of hemoglobin (P = 0.93 for a difference of 1 g/dl). The mean increase in the single-shot groups was 3 g/dl in 14 days. There was a significant reduction of iron stores in all groups. We conclude that single-shot rHuEPO 300 U/kg body weight corrects anemia just as effectively as divided doses on both intravenous and subcutaneous administration. The overall increase in Hb is only slight but preliminary results indicate that the effect can be enhanced by administrating iron intravenously and by an interval therapy with high-dose rHuEPO. The purpose of the present study was to compare the dosage requirements of recombinant human erythropoletin (rHuEPO) administered subcutaneously (SC) either one or three times weekly.
                A randomized, prospective study.
                The patients were recruited from two university hospitals and five county hospitals.
                Thirty-three anemic patients on continuous ambulatory peritoneal dialysis (CAPD) treatment for end-stage renal failure completed the study.
                Initially, all were treated with rHuEPO SC three times a week until hemoglobin blood levels (Hb) remained constant between 105 and 121 g/L for three months. Following randomization, 17 patients continued the same treatment schedule (group A), while 16 patients received the same dose, but administered only once weekly for three months (group B).
                The Hb levels and rHuEPO doses at the start and at the end of the three-month study period.
                In group A the median Hb at randomization was 118 g/L (109-119) (25-75 percentiles) and, after three months, was 113 g/L (106-119) (p = 0.13), while in group B the median Hb was 114 g/L (108-119) and 114 g/L (106-120), respectively (p = 0.50). In group A the weekly dose of rHuEPO remained virtually unchanged during the study period, 65 (55-86) and 66.3 (55-95) U/kg/week, respectively, while in group B it was increased from 60.2 (46-88) to 77 (60-90) U/kg/week. The 22% increase (p = 0.03) took place during the last two weeks.
                Our findings indicate that a once-weekly SC dosing regimen of rHuEPO in anemic CAPD patients was equally effective in maintaining a stable hemoglobin level as a thrice-weekly dosing regimen. A prospective randomized study of the use of recombinant human erythropoietin (rHuEPO) in children with chronic renal disease was conducted to assess dosing requirements and side effects. Forty-four children with chronic renal failure, aged 4 months to 21 years, were studied. Twenty-five patients were pre dialysis, 10 on peritoneal dialysis, and 9 on hemodialysis. Patients received either 150 U/kg per week or 450 U/kg per week divided thrice weekly of rHuEPO for 12 weeks or until target hemoglobin (Hb) was attained. Dose was then adjusted to maintain a normal Hb. Eighty-two percent of patients reached target Hb by 7.9+/-5.6 weeks (mean+/-SD); 95% of patients in the high-dose group and 66% in the low-dose group reached target Hb within 12 weeks. The overall median rHuEPO dose at target Hb was 150 U/kg per week. Hemodialysis patients tended to require more rHuEPO to maintain a normal Hb (median 250 U/kg per week). Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks. Iron deficiency and/or hypertension occurred in 30% of children. In conclusion, rHuEPO at 150 U/kg per week is safe and effective in treating anemia in children with chronic renal disease. The purpose of this study was to determine the efficacy of recombinant human erythropoietin (rHuEPO) given subcutaneously three times/week in patients with chronic renal failure and anemia (predialysis).
                Eleven patients with predialysis chronic renal failure participated in a double-blind, placebo-controlled study of subcutaneously administered erythropoietin. For 12 weeks, patients received either rHuEPO 100 mu/kg body weight three times/week subcutananeously or a placebo. After 12 weeks of placebo, patients now also received rHuEPO in a dose up to 150 mu/kg three times/week until target hematocrit was achieved. Throughout the study, blood pressure was monitored closely and blood work was obtained regularly for hemoglobin, hematocrit, reticulocyte count, and iron profile determinations.
                At 12 weeks, the hematocrit of the treated group had risen from 29% +/- 2% to 35% +/- 2% (p less than 0.001). The placebo group baseline hematocrit was 28% +/- 2% and at 12 weeks 26% +/- 2% After 12 weeks of rHuEPO therapy, the hematocrit of the prior placebo group was 32% +/- 2% (p less than 0.001 versus baseline). No significant change in biochemical parameters was noted. Mean blood pressure values were comparable before and after treatment. All protein ultimately required iron supplementation. In two patients, the rate of progression of renal failure appeared to increase as their hematocrit rose and rHuEPO was discontinued.
                It is concluded that rHuEPO given subcutaneously is an effective and safe therapy for patients with chronic renal failure who are anemic and who are not receiving dialysis. Anaemia in haemodialysis patients can be effectively treated with erythropoietin. We investigated whether subcutaneous (SC) epoetin ss administered once weekly was as effective as the same weekly dosage given in two to three divided doses.
                One hundred and fifty-eight patients (delivered Kt/V >1.0, where K=dialyser-renal urea clearance, t=dialysis time and V=filtration volume, obtained by urea kinetic modelling) were randomized to treatment with SC epoetin beta either once weekly (n=118), or to their original dosage two or three times weekly (control group, n=40) for 24 weeks. All patients received intravenous iron supplementation when necessary.
                Eight-eight patients in the once weekly group and 30 patients in the control group were treated for at least 16 weeks and are included in the analysis. Stable haemoglobin levels were maintained without epoetin dose increases in 73% of patients in both groups. Mean haemoglobin levels at randomization and after 16 and 24 weeks were 11.4, 11.1 and 11.1 g/dl, respectively, in the once weekly group compared with 11.2, 11.3 and 11.2 g/dl, respectively, in the control group. The mean weekly epoetin beta dosages at randomization and after 16 and 24 weeks were 102, 103 and 106 IU/kg bodyweight, respectively, in the once weekly group compared with 109, 109 and 115 IU/kg bodyweight, respectively, in the control group. No statistically significant between-group differences were apparent for changes in haemoglobin levels or epoetin beta dosages at week 24.
                Once weekly SC administration of epoetin beta is as safe and effective in maintaining haemoglobin levels in stable haemodialysis patients as two or three times weekly administration of the same total dose. By using the once weekly regimen, patients can avoid up to 104 injections per year. This would reduce clinic time for patients who do not self administer, and may also encourage self-administration and improve overall compliance. Patients undergoing chemotherapy for treatment of malignancy frequently experience clinically significant anemia. Myelosuppressive chemotherapy impairs erythropoiesis, which may not fully recover between treatment cycles. Recombinant human erythropoietin (rHuEPO) has been effectively introduced in anemic patients suffering from chronic renal failure. The present study was designed to assess, first, whether rHuEPO treatment decreases transfusion requirements in chemotherapy-induced anemia and, second, whether high-dose rHuEPO application is safe. STUDY DESIGN and
                Thirty consecutive anemic patients (hemoglobin <11 g/dl) receiving combination chemotherapy for primary malignant bone tumors were studied in a prospective, double-blind, randomized, Phase III trial. Patients received chemotherapy according to one of two German protocols, depending on histologic diagnosis. All subjects enrolled were randomly assigned either to receive 600 IU of rHuEPO per kg of body weight intravenously twice a week or to receive a placebo during chemotherapy. To obtain comparable data, an observation period of 20 weeks was chosen. Twenty-nine patients fulfilled the criteria and were eligible for statistical evaluation.
                Transfusion requirements were significantly decreased from Week 8 of therapy (p<0.05) in the treatment group. Therapeutic benefits were even more evident with continuation of therapy (Week 12, p = 0.03; Week 16, p = 0.016; Week 20, p = 0.002). The blood required was 2.1 units of red cells in the treatment group and 8.4 units of red cells in the placebo group. All patients tolerated rHuEPO with no serious side effects.
                These findings suggest that rHuEPO is an effective and well-tolerated therapeutic option for decreasing the transfusion requirements in chemotherapy-induced anemia. The administration of recombinant human erythropoietin (rHuEPO), started after the first 2 weeks of life, reduces the transfusion requirement in premature infants. However, its use throughout the first 2 weeks of life, when anemia results predominantly from phlebotomy losses, remains controversial. We investigated whether early use of rHuEPO would reduce the total transfusion requirement and/or the number of transfusions throughout the first 2 weeks of life.
                We randomized 114 infants with birth weight (BW) <1250 g to receive rHuEPO (1250 units/kg/week; IV; early group: n = 57) or placebo (late group: n = 57) from day 2 to day 14 of life; subsequently, all the patients received rHuEPO (750 units/kg/week, subcutaneously) for 6 additional weeks. All infants were given oral iron (6 mg/kg/day) and folic acid (2 mg/day).
                The early group showed higher hematocrit and reticulocyte counts than the late group in the first 3 weeks of life, but there was no difference in the total number of transfusions (early: 1.8 +/- 2.3 vs late: 1.8 +/- 2.5 transfusion/patient) or the transfusion requirement throughout the first 2 weeks of life (early:.8 +/- 1.1 vs late:.9 +/- 1.3) could be demonstrated. In infants with BW <800 g and total phlebotomy losses >30 mL/kg (n = 29), a lower number of transfusions was received by infants in the early group, compared with late group, from the second week to the end of the treatment (early: 3.4 +/- 1.1 vs late: 5.4 +/- 3.7 transfusion/patient). No clinical adverse effects were observed. Thrombocytosis was detected during the treatment with rHuEPO in 31% of the infants.
                In the whole population, the early administration of rHuEPO induced a rise of reticulocyte counts, but not enough to reduce the transfusion requirement. The most severely ill infants (BW <800 g and phlebotomy losses >30 mL/kg) seemed to benefit from early use of rHuEPO, and this deserves additional study.
There is no significant difference between once weekly versus thrice weekly subcutaneous administration of rHuEPO. Once weekly administration would require an additional 12 U/kg/wk for patients on haemodialysis, however this is based on one very small study. Cost of additional rHuEPO needs to assessed with regard to patient preference and compliance.