Pharmacologic doses of recombinant human erythropoietin in the treatment of myelodysplastic syndromes [see comments]

Abstract Twenty patients with myelodysplastic syndromes (MDS) entered a randomized, placebo-controlled, double-blind trial designed to evaluate the efficacy and toxicity of high doses of recombinant human erythropoietin (rhEPO). Patients completing the trial were eligible to receive rhEPO as part of an open-label study. Eighteen patients were transfusion dependent; 10 had refractory anemia (RA), and 10 had refractory anemia with ringed sideroblasts (RARS). A response to rhEPO was defined as an increase in hematocrit of 4 percentage points or more over baseline, or the elimination of all transfusions with the hematocrit stable at the baseline level. In the double-blind trial, 1 patient (12.5%) receiving rhEPO responded, as compared with no responses in the placebo group. Overall, responses occurred in 4 of 17 patients (24%) receiving rhEPO at a dose of 1,200 to 1,600 U/kg intravenously (IV) twice weekly. Changes in granulocyte or platelet counts were not observed. Despite the administration of high doses of rhEPO, toxicity attributable to rhEPO was not observed in either the double-blind or open-label study. Response to rhEPO was not significantly related to age, gender, type of MDS, time since diagnosis, time since initiation of transfusion therapy, or baseline serum EPO. These studies indicate that rhEPO can be administered safely in very high doses to patients with MDS and that 24% of these patients will respond with increased erythropoiesis.</jats:p

Pharmacologic doses of recombinant human erythropoietin in the treatment of myelodysplastic syndromes [see comments]

Twenty patients with myelodysplastic syndromes (MDS) entered a randomized, placebo-controlled, double-blind trial designed to evaluate the efficacy and toxicity of high doses of recombinant human erythropoietin (rhEPO). Patients completing the trial were eligible to receive rhEPO as part of an open-label study. Eighteen patients were transfusion dependent; 10 had refractory anemia (RA), and 10 had refractory anemia with ringed sideroblasts (RARS). A response to rhEPO was defined as an increase in hematocrit of 4 percentage points or more over baseline, or the elimination of all transfusions with the hematocrit stable at the baseline level. In the double-blind trial, 1 patient (12.5%) receiving rhEPO responded, as compared with no responses in the placebo group. Overall, responses occurred in 4 of 17 patients (24%) receiving rhEPO at a dose of 1,200 to 1,600 U/kg intravenously (IV) twice weekly. Changes in granulocyte or platelet counts were not observed. Despite the administration of high doses of rhEPO, toxicity attributable to rhEPO was not observed in either the double-blind or open-label study. Response to rhEPO was not significantly related to age, gender, type of MDS, time since diagnosis, time since initiation of transfusion therapy, or baseline serum EPO. These studies indicate that rhEPO can be administered safely in very high doses to patients with MDS and that 24% of these patients will respond with increased erythropoiesis.</jats:p

Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers

Abstract A double-blind, placebo-controlled study of the pharmacokinetics and safety of multiple doses of recombinant human erythropoietin [rHuEPO 150 or 300 U/kg either by intravenous (IV) bolus or subcutaneously (SC)] in normal male subjects demonstrated that rHuEPO had a dose- related effect on the hematocrit independent of the route of administration and that multiple doses of rHuEPO had no direct pressor effects. When rHuEPO was injected IV, a monoexponential decrease in serum EPO level was evident for 18 to 24 hours postdose. Absorption of SC injected rHuEPO occurred more slowly, with relatively low serum EPO levels being maintained for 48 hours. All rHuEPO antibody titer determinations were negative. With the exception of significant increases in hemoglobin and hematocrit, no clinically significant changes occurred. No hypertensive, convulsive, or thrombotic events were observed. Of the adverse experiences observed in 10 subjects, none was considered clinically significant, and none of the subjects dropped out because of adverse experiences.</jats:p

Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers

A double-blind, placebo-controlled study of the pharmacokinetics and safety of multiple doses of recombinant human erythropoietin [rHuEPO 150 or 300 U/kg either by intravenous (IV) bolus or subcutaneously (SC)] in normal male subjects demonstrated that rHuEPO had a dose- related effect on the hematocrit independent of the route of administration and that multiple doses of rHuEPO had no direct pressor effects. When rHuEPO was injected IV, a monoexponential decrease in serum EPO level was evident for 18 to 24 hours postdose. Absorption of SC injected rHuEPO occurred more slowly, with relatively low serum EPO levels being maintained for 48 hours. All rHuEPO antibody titer determinations were negative. With the exception of significant increases in hemoglobin and hematocrit, no clinically significant changes occurred. No hypertensive, convulsive, or thrombotic events were observed. Of the adverse experiences observed in 10 subjects, none was considered clinically significant, and none of the subjects dropped out because of adverse experiences.</jats:p

The level of haemoglobin in anaemic cancer patients correlates positively with quality of life

The aim of this study was to assess the relationship between haemoglobin level and quality-of-life in anaemic cancer patients. Patients, diagnosed with one of four cancers, were recruited if their haemoglobin level was <12 g dl(-1) (female) or <13 g dl(-1) (male). The condition-specific Functional Assessment of Cancer Therapy-Anaemia and the generic SF-36 were used to assess quality-of-life. Thirty-six per cent of the 179 recruited patients had breast cancer, 28% ovarian cancer, 25% lung cancer, and 11% multiple myeloma. Their mean (s.d.) haemoglobin level was 10.66 (1.04) g dl(-1). Partial correlations controlling for the potentially confounding effects of age, gender, and time since diagnosis found significant positive relationships between haemoglobin and all domains of the Functional Assessment of Cancer Therapy-Anaemia, and with all but two of the SF-36 domains. On linear regression controlling for the same factors, each unit haemoglobin rise equalled an average 8.19 Functional Assessment of Cancer Therapy-Anaemia, and an average 6.88 Functional Assessment of Cancer Therapy-Fatigue, increase. Haemoglobin accounted for a similar amount of variability (8%) in SF-36 scores. In conclusion, quality-of-life has been found to be significantly positively related to haemoglobin level in anaemic cancer patients. This suggests that normalisation of haemoglobin in cancer patients is likely to increase their quality-of-life. The greater sensitivity of the condition-specific Functional Assessment of Cancer Therapy-Anaemia compared with the generic SF-36 suggests that the Functional Assessment of Cancer Therapy-Anaemia can be used alone to assess quality-of life in this patient group